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The surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%-4.4%) of new TB patients and 18% (95% CI 7.6%-31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns. Aggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003-2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%-8.4%) among new TB patients and 11.4% (95% CI 9.4%-13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 countries (Azerbaijan, Bangladesh, Belarus, Pakistan, the Philippines, and South Africa). There were no cases of resistance to both pyrazinamide and levofloxacin among Hr-TB patients, except for the Philippines (1.8%, 95% CI 0.2-6.4) and Belarus (5.3%, 95% CI 0.1-26.0). Sequencing data for all genomic regions involved in isoniazid resistance were available for 4,563 patients. Among the 1,174 isolates that were resistant by either phenotypic testing or sequencing, 78.6% (95% CI 76.1%-80.9%) had resistance-conferring mutations in the katG gene and 14.6% (95% CI 12.7%-16.8%) in both katG and the inhA promoter region. For 6.8% (95% CI 5.4%-8.4%) of patients, mutations occurred in the inhA promoter alone, for whom an increased dose of isoniazid may be considered. The main limitations of this study are that most analyses were performed at the national rather than individual patient level and that the quality of laboratory testing may vary between countries. In this study, the prevalence of Hr-TB among TB patients was higher than the prevalence of rifampicin resistance globally. Many patients with Hr-TB would be missed by current diagnostic algorithms driven by rifampicin testing, highlighting the need for new rapid molecular technologies to ensure access to appropriate treatment and care. The low prevalence of resistance to pyrazinamide and fluoroquinolones among patients with Hr-TB provides further justification for the recommended modified treatment regimen.

Mycobacterium tuberculosis is a clonal pathogen proposed to have co-evolved with its human host for millennia, yet our understanding of its genomic diversity and biogeography remains incomplete. Here we use a combination of phylogenetics and dimensionality reduction to reevaluate the population structure of M. tuberculosis , providing an in-depth analysis of the ancient Indo-Oceanic Lineage 1 and the modern Central Asian Lineage 3, and expanding our understanding of Lineages 2 and 4. We assess sub-lineages using genomic sequences from 4939 pan-susceptible strains, and find 30 new genetically distinct clades that we validate in a dataset of 4645 independent isolates. We find a consistent geographically restricted or unrestricted pattern for 20 groups, including three groups of Lineage 1. The distribution of terminal branch lengths across the M. tuberculosis phylogeny supports the hypothesis of a higher transmissibility of Lineages 2 and 4, in comparison with Lineages 3 and 1, on a global scale. We define an expanded barcode of 95 single nucleotide substitutions that allows rapid identification of 69  M. tuberculosis sub-lineages and 26 additional internal groups. Our results paint a higher resolution picture of the M. tuberculosis phylogeny and biogeography. Mycobacterium tuberculosis is a clonal pathogen that has co-evolved with humans for millennia. Here, Freschi et al. reevaluate the population structure of M. tuberculosis , providing an in-depth analysis of the ancient Indo-Oceanic Lineage 1 and the modern Central Asian Lineage 3, and expanding our understanding of Lineages 2 and 4.

The present study discusses elevated groundwater arsenic (As) and fluoride (F⁻) concentrations in Mailsi, Punjab, Pakistan, and links these elevated concentrations to health risks for the local residents. The results indicate that groundwater samples of two areas of Mailsi, Punjab were severely contaminated with As (5.9–507 ppb) and F⁻ (5.5–29.6 ppm), as these values exceeded the permissible limits of World Health Organization (10 ppb for As and 1.5 ppm for F⁻). The groundwater samples were categorized by redox state. The major process controlling the As levels in groundwater was the adsorption of As onto PO₄ ³⁻ at high pH. High alkalinity and low Ca²⁺ and Mg²⁺ concentrations promoted the higher F⁻ and As concentrations in the groundwater. A positive correlation was observed between F⁻ and As concentrations (r = 0.37; n = 52) and other major ions found in the groundwater of the studied area. The mineral saturation indices calculated by PHREEQC 2.1 suggested that a majority of samples were oversaturated with calcite and fluorite, leading to the dissolution of fluoride minerals at alkaline pH. Local inhabitants exhibited arsenicosis and fluorosis after exposure to environmental concentration doses of As and F⁻. Estimated daily intake (EDI) and target hazard quotient (THQ) highlighted the risk factors borne by local residents. Multivariate statistical analysis further revealed that both geologic origins and anthropogenic activities contributed to As and F⁻ contamination in the groundwater. We propose that pollutants originate, in part, from coal combusted at brick factories, and agricultural activities. Once generated, these pollutants were mobilized by the alkaline nature of the groundwater.

Climatic warming and the resulting increase in soil respiration affect the sequestration and transformation of soil components, as well as their transport to the surrounding ecosystems. However, the integrated mechanistic details of these processes remain elusive. Here we apply an extraction protocol that utilizes two sequential extraction techniques to isolate and analyze both dissolved and solid-state soil components and to assess their dark and photoinduced fates under varying temperature conditions, intended to simulate global warming. We observe a net increase in total sulfur (1.2–41.0%), which is ascribed to S sequestration-redox reactions involving both sulfide oxidation to S o ⇌ SO 4 2− and the reverse (S 2− /S 2 2− ⇌ SO 4 2– ) via SO 4 2– plus soil organic sulfur plus sulfides/pyrites (SOS + S n 2− ) decrease and/or increase under sunlight, dark, and control conditions. Higher transformation and mineralization of various components occurs in dark/microbial conditions by the wide day-night experimental temperature variation (10–42 °C) in comparison with the control at constant temperature (25 °C). Remarkably, the photosynthetically-derived soil organic carbon (SOC)/humic substances (HS)-bound mineral neoformation through uptake and sequestration of various components, including As and Hg, is specifically detected under sunlight and control conditions. A major role is played by seven redox-active metals (Fe, Mn, Cu, Hg, Ni, As, and U), which are involved in both organo-mineral complexation and redox processes. Importantly, the dark/microbial dissolution of iron minerals is primarily responsible for the increased export of water-extractable or labile As (33.8–89.7%) over a period of 0-150 days, with no evidence of sequestration. In contrast, As sequestration and relatively low water-extractable As export occur under sunlight (9.0-25.5%) and control (17.4–38.4%) samples. A net decrease in Hg levels is observed over a period of 0 to 150 days, along with relatively low sequestration across three treatments, appearing the highest losses under sunlight conditions (9.8–17.4%) when compared to dark (5.2–11.4%) and control (3.6–11.6%) samples. This effect may be attributed to the reduction of Hg(I, II)‒DOM into gaseous Hg⁰. These findings could assist in managing soil components and predicting where and when the side effects of global warming-such as erosion-associated mobilization of soil components, including As and Hg into surrounding surface water, groundwater, and the atmosphere-are likely to manifest.

Soil humic substances (HSs) typically alter their electrochemical behaviours in the pH range of 1–12, which simultaneously regulates the stability of organo-minerals by modifying the HS functionalities. This process facilitates both biotic and abiotic transformations, which consequently leads to the export of degradative byproducts (e.g. HS components, nutrients) from soils into surrounding aquatic environments through water and/or rainwater discharges. However, the solubility features, environmental consequences, and mechanisms of HSs, including humic acids (HAs), fulvic acids (FAs), and protein-like substances (PLSs), under different pHs remain unclear. To respond to these issues, we used two soil extracts which were fractionated in the pH range from 12–1. The pH-dependent presence or absence of fluorescence peaks in the individual HS components reflected their functional group proton/electron exchange features at both low and high pH values, which were related to their solubility or insolubility. In particular, alkaline pH (≥pH 9) yielded the anionic forms (-O- and -COO-) of phenolic OH and carboxyl groups of HACS, resulting in decreased electron/proton transfer from HS functionalities, as indicated by the decline of fluorescence peak maxima, whereas the protonic functionalities (e.g. –COOH, –OH) of HSs at lower pH resulted in the formation of highly available and remaining uncomplexed HS forms. The solubility of HA fractions increases with increasing pH, whereas their insolubility increases with decreasing pH, which determines their initial precipitation at pH 6 and final precipitation at pH 1, amounting approximately to 39.1 %–49.2 % and 3.1 %–24.1 % of the total dissolved organic matter (DOM), respectively, in the two soils. Elemental analysis results demonstrated that the C and N contents of HALS-pH 6 were lower and that those of O, S, and H were higher than those of HACS-pH 6, suggesting the preservation of C and N without S acquisition in HACS-pH 6, possibly because of their being complexed with minerals, which, in turn, would determine the insolubility of the HACS-pH 6 fraction. FACS + PLSCS showed relatively higher C and S contents and lower O% with respect to FALS + PLSLS, implying that FACS + PLSCS would remain under mineral protection. Fourier transform infrared (FTIR) results show significantly reduced infrared absorptions (e.g. 3300–3600 and 800–1200 cm−1) of HACS-pH 6 with respect to HALS-pH 6, suggesting the existence of strong intermolecular interactions among HA functional groups, possibly due to insoluble forms originally complexed with minerals. However, FALS + PLSLS exhibited stronger bands at 3414–3429 and 1008–1018 cm−1 than FACS + PLSCS, implying a strong interaction among functional groups possibly derived from various organo-mineral complexes in FACS + PLSCS. These results would indicate that HS insolubility arises via organo-metal and organo-mineral interactions at alkaline pH, along with HApH 6 insolubility via rainwater/water discharge, whereas HApH 2 + FA + PLS appears to be soluble at acidic pH, thereby being transported in ambient waters via rainwater/water discharge and groundwater infiltration. Therefore, the pH-dependent behaviour of soil HSs greatly contributes to a better understanding of the progressive transformation, mobility/transportation, and immobility/accumulation of HS components under various environmental conditions, with relevant implications for sustainable soil management practices and soil DOM dynamics.

Mountainous rivers are critical in transporting dissolved organic carbon (DOC) from terrestrial environments to downstream ecosystems. However, how geomorphologic factors and anthropogenic impacts control the composition and export of DOC in mountainous rivers remains largely unclear. Here, we explore DOC dynamics in three subtropical mountainous catchments (i.e., the Yinjiang, Shiqian, and Yuqing catchments) in southwest China, which are heavily influenced by anthropogenic activities. Water chemistry, stable and radioactive carbon isotopes of DOC (δ13CDOC and Δ14CDOC), and optical properties (UV absorbance and fluorescence spectra) were employed to assess the biogeochemical processes and controlling factors on riverine DOC. The radiocarbon ages of DOC in the Yinjiang River varied widely from 928 years BP to the present. Stepwise multiple regression analyses and partial least square path models revealed that geomorphology and anthropogenic activities were the major drivers controlling DOC concentrations and DOM characteristics. Catchments with higher catchment slope gradients were characterized by lower DOC concentrations, enriched δ13CDOC and Δ14CDOC, and more aromatic dissolved organic matter (DOM), which were opposite to catchments with gentle catchment slopes. Variabilities in DOC concentrations were also regulated by land use, with higher DOC concentrations in urban and agricultural areas. Furthermore, DOM in catchments with a higher proportion of urban and agricultural land uses was less aromatic, less recently produced, and exhibited a higher degree of humification and more autochthonous humic-like DOM. This research highlights the significance of incorporating geomorphologic controls on DOC sources and anthropogenic impacts on DOM composition into the understanding of DOC dynamics and the quality of DOM in mountainous rivers, which are globally abundant.

Ocean acidification, a complex phenomenon that lowers seawater pH, is the net outcome of several contributions. They include the dissolution of increasing atmospheric CO2 that adds up with dissolved inorganic carbon (dissolved CO2, H2CO3, HCO3−, and CO32−) generated upon mineralization of primary producers (PP) and dissolved organic matter (DOM). The aquatic processes leading to inorganic carbon are substantially affected by increased DOM and nutrients via terrestrial runoff, acidic rainfall, increased PP and algal blooms, nitrification, denitrification, sulfate reduction, global warming (GW), and by atmospheric CO2 itself through enhanced photosynthesis. They are consecutively associated with enhanced ocean acidification, hypoxia in acidified deeper seawater, pathogens, algal toxins, oxidative stress by reactive oxygen species, and thermal stress caused by longer stratification periods as an effect of GW. We discuss the mechanistic insights into the aforementioned processes and pH changes, with particular focus on processes taking place with different timescales (including the diurnal one) in surface and subsurface seawater. This review also discusses these collective influences to assess their potential detrimental effects to marine organisms, and of ecosystem processes and services. Our review of the effects operating in synergy with ocean acidification will provide a broad insight into the potential impact of acidification itself on biological processes. The foreseen danger to marine organisms by acidification is in fact expected to be amplified by several concurrent and interacting phenomena.

Soil biogenic components are subject to continuous sequestration, and export from soils into the surrounding air and water environments. However, the processes involving the stability or lability of their mineral states remain still unclear. To assess these issues, we have measured various biogenic components in a number of agricultural, forest, grassland, and deep soils, as well as desert sands from Inner Mongolia, both in the solid state and liquid extracts. The contents of soil organic carbon (SOC) and soil total nitrogen (STN) were higher in soils than in sands, whilst those of soil total sulfur (STS) and inorganic carbon were higher in sands and deeper soils. The significant positive correlations found between STS and SOC, and STN, and their significant negative correlations with pH and δ 13 C-SOC in all soils suggest a pH-dependent sequestration of C, N, and S. The decreased stability of organo-mineral complexes at acidic pH, resulting from the acidification of humic substance (HS) functionalities, leads to a higher availability of nutrients that facilitates the sequestration of soil organic matter (SOM). Conversely, an increase in pH enhances the stability of organo-mineral complexes by promoting negatively charged HS functionalities, which reduces the availability of nutrients and the sequestration of SOM. The δ 13 C-SOC enrichment in desert sands (-17.63 to -7.10‰) and its depleted values in soils (-24.9 to -18.8‰) suggest the occurrence of C sequestration in desert, via uptake of enriched atmospheric CO 2 (-8.4‰). The fluorescence spectra of humic substance components and their molecular weights in sands were typically different from those of soils. The predominant relatively low molecular weight (MW) (< 15–25 kDa) of alkali-extracted (complexed state: CS) components and the relatively high MW (> 25 − 15 kDa) of water-extracted (labile state: LS) components of all soils suggest, respectively, their involvement in organo-mineral complexes and for export into the surrounding environment. The quantities of LS and CS soil components differ significantly on dependence of soil characteristics, implying their corresponding lability or stability in soils. These findings will provide useful input for the management of the corresponding soil/sand ecosystems.

Fluorescence (excitation-emission matrices, EEMs) spectroscopy coupled with PARAFAC (parallel factor) modelling and UV-Vis (ultraviolet visible) spectra were used to ascertain the sources, distribution and biogeochemical transformation of dissolved organic matter (DOM) in the Duliujian River catchment. Dissolved organic carbon (DOC), chromophoric dissolved organic matter (a335) (CDOM), and hydrophobic components (a260) were higher in summer than in other seasons with 53.3 m−1, while aromaticity (SUVA254) was higher in spring. Four fluorescent components, namely terrestrial humic acid (HA)-like (A/C), terrestrial fulvic acid (FA)-like (A/M), autochthonous fulvic acid (FA)-like (A/M), and protein-like substances (Tuv/T), were identified using EEM-PARAFAC modelling in this river catchment. The results demonstrated that terrestrial HA-like substances enhance its contents in summer ARE compared with BRE, whilst terrestrial FA-like substances were newly input in summer ARE, which was entirely absent upstream and downstream, suggesting that rain events could significantly input the terrestrial soil-derived DOM in the ambient downward catchments. Autochthonous FA-like substances in summer BRE could derive from phytoplankton in the downstream waters. The results also showed that DOM from wetland exhibited lower fluorescent intensity of humic-like peak A/C and fulvic-like peak A/M, molecular weight (SR) and humification index (HIX) during the low-flow season. Built-up land, cropland, and unused land displayed higher a335 (CDOM). A higher proportion of forest and industrial land in the SCs showed higher SUVA254 values. Humic-like moiety, molecular weight and aromaticity were more responsive to land use during stormflow in summer. Rainfall could increase the export of soil DOM from cropland and unused land, which influences the spatial variation of HIX. The results in this study highlighted that terrestrial DOM has a significant influence on the biogeochemical alterations of DOM compositions and thus water quality in the downward watershed catchments, which might significantly vary according to the land-use types and their alterations by human activities.

In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87–94) for rpoB (rifampicin resistance), 86% (74–93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39–68) for pncA (pyrazinamide resistance), 85% (77–91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81–92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.