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Understanding ecological niches of major tick species and prevalent tick-borne pathogens is crucial for efficient surveillance and control of tick-borne diseases. Here we provide an up-to-date review on the spatial distributions of ticks and tick-borne pathogens in China. We map at the county level 124 tick species, 103 tick-borne agents, and human cases infected with 29 species (subspecies) of tick-borne pathogens that were reported in China during 1950−2018. Haemaphysalis longicornis is found to harbor the highest variety of tick-borne agents, followed by Ixodes persulcatus , Dermacentor nutalli and Rhipicephalus microplus . Using a machine learning algorithm, we assess ecoclimatic and socioenvironmental drivers for the distributions of 19 predominant vector ticks and two tick-borne pathogens associated with the highest disease burden. The model-predicted suitable habitats for the 19 tick species are 14‒476% larger in size than the geographic areas where these species were detected, indicating severe under-detection. Tick species harboring pathogens of imminent threats to public health should be prioritized for more active field surveillance. Ticks are an important vector of disease in China, posing threats to humans, livestock and wild animals. Here, Zhao et al. compile a database of the distributions of the 124 tick species known in China and 103 tick-borne pathogens and predict the additional suitable habitats for the predominant vector species.

The C-terminus of α-tubulin undergoes a detyrosination/tyrosination cycle and dysregulation of this cycle is associated with cancer and other diseases. The molecular mechanisms of tubulin tyrosination are well studied, however it has remained unknown how tyrosine is cleaved from the tubulin tail. Here, we report the crystal structure of the long-sought detyrosination enzyme, the VASH2/SVBP heterodimer at 2.2 Å resolution and the structure of the tail/VASH2/SVBP complex at 2.5 Å resolution. VASH2 possesses a non-canonical Cys-His-Ser catalytic architecture for tyrosine cleavage. The dynamics of the α1- and α2- helices of VASH2 are related to the insolubility of VASH2. SVBP plays a chaperone-like role by extensively interacting with VASH2 and stabilizing these dynamic helices. A positively charged groove around the catalytic pocket and the α1- and α2- helices of VASH2 targets the tubulin tail for detyrosination. We provide insights into the mechanisms underlying the cycle of tubulin tyrosine cleavage and religation. The VASH2/SVBP heterodimer catalyzes the detyrosination of the α-tubulin C-terminus. Here the authors provide insights into the tubulin detyrosination mechanism by determining the crystal structures of VASH2/SVBP and VASH2/SVBP in complex with a tubulin tail peptide.

Recent studies have demonstrated that gastric cancer stem cells (CSCs) are a rare sub-group of gastric cancer (GC) cells and have an important role in promoting the tumor growth and progression of GC. In the present study, we demonstrated that the glycolytic enzyme Enolase 1 (ENO1) was involved in the regulation of the stem cell-like characteristics of GC cells, as compared to the parental cell lines PAMC-82 and SNU16, the expression of ENO1 in spheroids markedly increased. We then observed that ENO1 could enhance stem cell-like characteristics, including self-renewal capacity, cell invasion and migration, chemoresistance, and even the tumorigenicity of GC cells. ENO1 is known as an enzyme that is involved in glycolysis, but our results showed that ENO1 could markedly promote the glycolytic activity of cells. Furthermore, inhibiting glycolysis activity using 2-deoxy- d -glucose treatment significantly reduced the stemness of GC cells. Therefore, ENO1 could improve the stemness of CSCs by enhancing the cells’ glycolysis. Subsequently, to further confirm our results, we found that the inhibition of ENO1 using AP-III-a4 (ENOblock) could reduce the stemness of GC cells to a similar extent as the knockdown of ENO1 by shRNA. Finally, increased expression of ENO1 was related to poor prognosis in GC patients. Taken together, our results demonstrated that ENO1 is a significant biomarker associated with the stemness of GC cells.

Background The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status. Methods Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. . Conclusions In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.

Background: Adenosine administration can improve coronary blood flow in patients undergoing primary percutaneous coronary intervention (PCI); however, the therapeutic effects of adenosine on ST resolution and major adverse cardiovascular events (MACEs) after PCI remain unclear. This study aimed to assess the therapeutic effects of adjunctive adenosine administration on patients with acute myocardial infarction (AMI) undergoing PCI using a meta-analytic approach. Methods: We conducted a systematic search across PubMed, Embase, and the Cochrane Library to identify eligible randomized controlled trials (RCTs) published from inception through to March 2024. Primary outcomes included ST resolution and MACEs. The pooled analyses were all conducted using the random-effects model. Additionally, exploratory analyses were carried out through the application of sensitivity and subgroup analyses. Results: Twenty-one RCTs involving 2467 patients with AMI were selected for the meta-analysis. Adenosine significantly increased the incidence of ST resolution (relative risk [RR]: 1.30; 95% confidence interval [CI]: 1.15–1.46; p < 0.001), while it significantly reduced the risk of MACEs (RR: 0.67; 95% CI: 0.51–0.87; p = 0.003). Moreover, the use of adenosine was associated with reduced incidences of no reflow (RR: 0.35; 95% CI: 0.24–0.52; p < 0.001) and myocardial blush grade (MBG) 0 to 1 (RR: 0.75; 95% CI: 0.58–0.99; p = 0.041). Furthermore, adenosine significantly reduced the risk of heart failure (RR: 0.66; 95% CI: 0.44–0.99; p = 0.044). Finally, adenosine use was associated with a lower creatine kinase-MB (CK-MB) peak value (weighted mean difference: –36.94; 95% CI: –73.76– –0.11; p = 0.049). Conclusions: This study revealed that adenosine use was associated with an increased incidence of ST resolution, and reduced risk of MACEs. The INPLASY registration: INPLASY202510051, https://inplasy.com/inplasy-2025-1-0051/.

This study investigates the lightest and second-lightest Higgs bosons at around 95 GeV (which is only a hypothetical scenario) and 125 GeV respectively within the CP-violating next to minimum B-L supersymmetric model (NB-LSSM). In the NB-LSSM, the CP violation in the Higgs potential leads to the mixing mass terms between the CP-even and CP-odd Higgs fields. Thus, one has to consider a ( 10 × 10 ) -dimensional mass matrix for the neutral Higgs boson. These potential mixing effects may lead to drastic variations on the neutral Higgs boson masses. Besides, the neutral Higgs bosons predicted in the NB-LSSM may strongly mix with one another, thereby significantly modifying the couplings of the Higgs bosons to the fermions or gauge bosons. It is found that the specific parameters g YB , tan β , T κ , T λ , ⋯ and CP-violating phases θ 1 , 2 , 3 , 4 , 6 , 7 , 8 in the NB-LSSM affect the theoretical predictions on the Higgs boson mass and corresponding signal strengths significantly. And the theoretical predictions on the signal strengths of SM-like Higgs decay channels and excess signals at around 95 GeV are fitted well to the observed experimental data.

Dysregulation of the balance between cell proliferation and cell death is a central feature of malignances. Death-associated protein kinase 3 (DAPK3) regulates programmed cell death including apoptosis and autophagy. Our previous study showed that DAPK3 downregulation was detected in more than half of gastric cancers (GCs), which was related to tumor invasion, metastasis, and poor prognosis. However, the precise molecular mechanism underlying DAPK3-mediated tumor suppression remains unclear. Here, we showed that the tumor suppressive function of DAPK3 was dependent on autophagy process. Mass spectrometry, in vitro kinase assay, and immunoprecipitation revealed that DAPK3 increased ULK1 activity by direct ULK1 phosphorylation at Ser556. ULK1 phosphorylation by DAPK3 facilitates the ULK1 complex formation, the VPS34 complex activation, and autophagy induction upon starvation. The kinase activity of DAPK3 and ULK1 Ser556 phosphorylation were required for DAPK3-modulated tumor suppression. The coordinate expression of DAPK3 with ULK1 Ser556 phosphorylation was confirmed in clinical GC samples, and this co-expression was correlated with favorable survival outcomes in patients. Collectively, these findings indicate that the tumor-suppressor roles of DAPK3 in GC are associated with autophagy and that DAPK3 is a novel autophagy regulator, which can directly phosphorylate ULK1 and activate ULK1. Thus, DAPK3 might be a promising prognostic autophagy-associated marker.

Background The ongoing transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and its expansion to other regions are raising concerns of a potential pandemic. An in-depth analysis about both population and molecular epidemiology of this pathogen is needed. Methods MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports, supplemented by other reliable sources. Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models, respectively. Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV. Results A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7% (95% CI : 30.9‒34.6%). Saudi Arabia accounted for 83.6% of the cases. Age of ≥ 65 years old, underlying conditions and ≥ 5 days delay in diagnosis were independent risk factors for death. However, a history of animal contact was associated with a higher risk (adjusted OR  = 2.97, 95% CI : 1.10–7.98) among female cases < 65 years but with a lower risk (adjusted OR  = 0.31, 95% CI : 0.18–0.51) among male cases ≥ 65 years old. Diffusion of the disease was fastest from its origin in Saudi Arabia to the east, and was primarily driven by the transportation network. The most recent sub-clade C5.1 (since 2013) was associated with non-synonymous mutations and a higher mortality rate. Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV. Conclusions MERS-CoV remains primarily locally transmitted in the Middle East, with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases. Animal contact is associated with a higher risk of death, but the association differs by age and sex. Transportation network is the leading driver for the spatial diffusion of the disease. These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic. Graphical abstract

The geographic expansion of mosquitos is associated with a rising frequency of outbreaks of mosquito-borne diseases (MBD) worldwide. We collected occurrence locations and times of mosquito species, mosquito-borne arboviruses, and MBDs in the mainland of China in 1954−2020. We mapped the spatial distributions of mosquitoes and arboviruses at the county level, and we used machine learning algorithms to assess contributions of ecoclimatic, socioenvironmental, and biological factors to the spatial distributions of 26 predominant mosquito species and two MBDs associated with high disease burden. Altogether, 339 mosquito species and 35 arboviruses were mapped at the county level. Culex tritaeniorhynchus is found to harbor the highest variety of arboviruses (19 species), followed by Anopheles sinensis (11) and Culex pipiens quinquefasciatus (9). Temperature seasonality, annual precipitation, and mammalian richness were the three most important contributors to the spatial distributions of most of the 26 predominant mosquito species. The model-predicted suitable habitats are 60–664% larger in size than what have been observed, indicating the possibility of severe under-detection. The spatial distribution of major mosquito species in China is likely to be under-estimated by current field observations. More active surveillance is needed to investigate the mosquito species in specific areas where investigation is missing but model-predicted probability is high.

Background Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM. Methods A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated. Results A total of 464 MACEs were documented. Both Kaplan–Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24–2.70, p < 0.05). However, no significant association was observed for high sdLDL plus Pre-DM or NGR. Conclusions The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD, suggesting that sdLDL may be useful for CAD risk stratification in DM.