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With the help of quantum key distribution (QKD), two distant peers are able to share information-theoretical secure key bits. Increasing the key rate is ultimately significant for the applications of QKD in the lossy channel. However, it has been proven that there is a fundamental rate-distance limit, called the linear bound, which restricts the performance of all existing repeaterless protocols and realizations. Surprisingly, a recently proposed protocol, called twin-field (TF) QKD, can beat the linear bound with no need for quantum repeaters. Here, we present one of the first implementations of the TF-QKD protocol and demonstrate its advantage of beating the linear bound at a channel distance of 300 km. In our experiment, a modified TF-QKD protocol that does not assume phase postselection is considered, and thus a higher key rate than the original one is expected. After controlling the phase evolution of the twin fields traveling through hundreds of kilometers of optical fibers, the implemented system achieves high-visibility single-photon interference and allows stable and high-rate measurement-device-independent QKD. Our experimental demonstration and results confirm the feasibility of the TF-QKD protocol and its prominent superiority in long-distance key distribution services.

Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria 1 . Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection 2 , 3 . Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet (X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet (X4)-positive E.   coli strains, including isolates co-harbouring mcr-1 , have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics. Plasmid-encoded tet (X) genes from Escherichia coli in China confer high-level tigecycline resistance.

Background The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet (X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants. Methods Herein, we conducted a multiregional whole-genome sequencing study of tet (X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet (X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet (X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses. Results We identified 193 tet (X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet (X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet (X3) ( n  = 188) and tet (X4) ( n  = 5), two tet (X5) variants, tet (X5.2) ( n  = 36) and tet (X5.3) ( n  = 4), were also found together with tet (X3) or tet (X4) but without additive effects on tetracyclines. These tet (X)-positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2–8 μg/mL) and omadacycline (8–16 μg/mL). Genetic analysis revealed that different tet (X) variants shared an analogous IS CR2 -mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet (X)-like genes through horizontal transfer. Conclusions Four tet (X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of IS CR2 in mobilizing tet (X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.

Transcranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate neurons in the brain and has been widely applied in the field of clinical neuromodulation. However, traditional TMS has limitations in terms of focality and stimulation depth, making it unable to achieve precise modulation of deep brain regions. As the stimulation depth increases, the focal area expands, potentially stimulating nontarget regions and causing negative side effects. Moreover, strongly induced electric fields can lead to adverse effects such as seizures. Temporal interference transcranial magnetic stimulation (TI-TMS) is a novel noninvasive neuromodulation technique that has considerable potential for reducing the focal area and increasing the stimulation depth. To study the mechanisms and effects of TI-TMS, this research first established a TI-TMS simulation platform based on a five-layer spherical model. This paper designed a double curved-elliptical coil structure, increasing the stimulation depth of the TI-TMS to 5.02 cm while reducing the focal area to 18.61 cm 2 . Finally, a TI-TMS system was developed, with a focus on the design and development of the insulated-gate bipolar transistor (IGBT) driving circuit and the coil capacitor resonance part. The current amplitude and frequency in the coils were measured to validate the system’s effectiveness. This study confirmed that TI-TMS can effectively stimulate deep brain regions and provide new insights for the application of TMS in the rehabilitation of neurological diseases.

Coal is the primary source of China’s carbon emissions due to the energy structure and its resource endowment. This reality creates enormous pressure and impetus for low-carbon pathways of coal production and consumption. Based on a literature review on carbon emissions accounting methods, this paper builds a source-driven CO2 emissions accounting model for the coal development sector using the emissions factor method. Scenario analysis is employed to predict future carbon emission equivalents and to indicate possible implications for climate change mitigation in this sector. Carbon emissions from coal development are mainly derived from coal mine gas emissions, which yield 62% of the sector’s total carbon emissions, followed by energy consumption. The recent decline in coal mining-driven CO2 emissions is mainly due to the strict deployment of coal mine gas and the changing structure of coal mines. The results from the scenarios suggest that the carbon emissions reduction potential will largely be determined by technology innovation in the coal mine gas industry. Policy implications for further addressing carbon emissions from the supply side of the coal industry include improvements in energy efficiency and coal mine gas extraction and utilization.

Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA was measured using the TCMSP server, and potential targets of SAA were identified by PharmMapper and DRAR-CPI. Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and drug-target-pathway networks were constructed to give a visual view. The results showed that SAA has good druggability, and 13 putative protein targets were identified. Network analysis showed that these targets were associated with cancer, metabolism and other physiological processes. In summary, SAA is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects.

Visualization and quantification of important biomolecules like glutathione (GSH) in live cells are highly important. The existing methods are mostly from optical detection and lack of atomic resolution on the activity of GSH. Here, we present a sensitive 19F-NMR method to quantify real-time variations of GSH in live cells in a reversible manner. This NMR method prevents extracellular leakage and irreversible consumption of intracellular GSH during the detection. The high performance of the reactive 19F-probe enables accurate determination of intracellular GSH content at atomic resolution, from which information on GSH variations with respect to the extracellular and intracellular conditions can be inferred. In addition, we demonstrate the applicability of this NMR method to quantify the GSH levels between different live cell lines and to disclose the distinct differences between the intracellular environment and cell lysates. We foresee the application of 19F-NMR to monitor real-time variations of intracellular GSH levels in relation to GSH-involved central cellular processes.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP‐43 aggregates. Recent evidence has been indicated that phosphorylated TDP‐43 (pTDP‐43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP‐43 detectable in routine biopsied muscles? (ii) Can detection of pTDP‐43 aggregation discriminate between ALS and non‐ALS patients? (iii) Can pTDP‐43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non‐ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP‐43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP‐43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non‐ALS controls (16/54; p < 0.001). The pTDP‐43 aggregates were mainly close to the sarcolemma. Using a semi‐quantified pTDP‐43 aggregates score, we applied a cut‐off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof‐of‐concept for the detection of pTDP‐43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS. To explore whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS, we conducted a diagnostic study in 18 ALS patients and 54 randomly matched controls from ALS and muscular disease cohorts. Our results indicated that pTDP‐43 was more prone to accumulation in ALS patients, enabling differentiation between ALS and non‐ALS patients with high sensitivity and specificity. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions.

Background Long non-coding RNA H19 (H19) plays an important role by regulating protein expression in different tissues and organs of the body. However, whether H19 induces hypoxia/reoxygenation (h/R) injury via increase of autophagy in the hepatoma carcinoma cells is unknown. Results H19 was expressed in the hepatoma carcinoma cells (Hep G2 and HCCLM3 cells) and its expression was most in 8 h/24R. The knockdown of H19 and 3-MA (an autophagy inhibitor) protected against h/R-induced apoptosis, cell damage, the expression of cleaved caspase-3 and cleaved caspase-9, the release of cytochrome c (Cyt c ). The knockdown of H19 and 3-MA also decreased the autophagic vesicles (AVs) and the expression of Beclin-1 and the ration of LC3-II/LC3-I, and increased cell viability, the expression of Bcl-2 and P62 and the phosphorylation of PI3K, Akt and mTOR. In addition, chloroquine (CQ, an inhibitor of autophagy flux) markedly decreased formation of autophagy flux (the ration of LC3-II/LC3-I). The results of the knockdown of H19 group were similar to those of the 3-MA (or CQ) group. Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. The knockdown of H19 cancelled the effect of rapamycin. The overexpression of H19 further expanded h/R-induced increase of the ration of LC3-II/LC3-I and decrease of the phosphorylated PI3K, Akt and mTOR. Conclusions Our results suggest that the long non-coding RNA H19 induces h/R injury by up-regulation of autophagy via activation of PI3K–Akt–mTOR pathway in the hepatoma carcinoma cells.

New wave excitations are revealed for a (3 + 1)-dimensional nonlinear evolution equation to enrich nonlinear wave patterns in nonlinear systems. Based on a new variable separation solution with two arbitrary variable separated functions obtained by means of the multilinear variable separation approach, localized excitations of N dromions, N × M lump lattice and ring soliton lattice are constructed. In addition, it is observed that soliton molecules can be composed of diverse “atoms” such as the dromions, lumps and ring solitons, respectively. Elastic interactions between solitons and soliton molecules are graphically demonstrated.