Exploring the seasonality and optimal control strategy of HIV/AIDS epidemic in China: The impact of seasonal testing.

In this work, we investigate how the seasonal variation in the number of individuals who are tested for an HIV antibody in outpatient clinics affects the HIV transmission patterns in China, which has not been well studied. Based on the characteristics of outpatient testing data and reported cases, we establish a periodic infectious disease model to study the impact of seasonal testing on HIV transmission. The results indicate that the seasonal testing is a driving factor for the seasonality of new cases. We demonstrate the feasibility of ending the HIV/AIDS epidemic. We find that the diagnostic rates related to testing play a crucial role in controlling the size of the epidemic. Specifically, when considering minimizing both infected individuals and diagnostic rates, the level of attention paid to undiagnosed infected individuals is always positively correlated with the optimal diagnostic rates, while the optimal diagnostic rates are negatively correlated with the size of the epidemic at the terminal time.

ADATs: roles in tRNA editing and relevance to disease.

Transfer RNAs (tRNAs) play central roles in protein biosynthesis. Post-transcriptional RNA modifications affect tRNA function and stability. Among these modifications, RNA editing is a widespread RNA modification in three domains of life. Proteins of the adenosine deaminase acting on tRNA (ADAT) family were discovered more than 20 years ago. They catalyze the deamination of adenosine to inosine (A-to-I) or cytidine to uridine (C-to-U) during tRNA maturation. The most studied example is the TadA- or ADAT2/3-mediated A-to-I conversion of the tRNA wobble position in the anticodon of prokaryotic or eukaryotic tRNAs, respectively. This review provides detailed information on A-to-I and C-to-U editing of tRNAs in different domains of life, presents recent new findings on ADATs for DNA editing, and finally comments on the association of mutations in the ADAT3 gene with intellectual disability.

Machine learning guided prediction of warfarin blood levels for personalized medicine based on clinical longitudinal data from cardiac surgery patients: a prospective observational study.

BACKGROUND: Warfarin is a common oral anticoagulant, and its effects vary widely among individuals. Numerous dose-prediction algorithms have been reported based on cross-sectional data generated via multiple linear regression or machine learning. This study aimed to construct an information fusion perturbation theory and machine learning prediction model of warfarin blood levels based on clinical longitudinal data from cardiac surgery patients. METHODS AND MATERIAL: The data of 246 patients were obtained from electronic medical records. Continuous variables were processed by calculating the distance of the raw data with the moving average (MA ∆vki(sj)), and categorical variables in different attribute groups were processed using Euclidean distance (ED ǁ∆vk(sj)ǁ). Regression and classification analyses were performed on the raw data, MA ∆vki(sj), and ED ǁ∆vk(sj)ǁ. Different machine-learning algorithms were chosen for the STATISTICA and WEKA software. RESULTS: The random forest (RF) algorithm was the best for predicting continuous outputs using the raw data. The correlation coefficients of the RF algorithm were 0.978 and 0.595 for the training and validation sets, respectively, and the mean absolute errors were 0.135 and 0.362 for the training and validation sets, respectively. The proportion of ideal predictions of the RF algorithm was 59.0%. General discriminant analysis (GDA) was the best algorithm for predicting the categorical outputs using the MA ∆vki(sj) data. The GDA algorithm's total true positive rate (TPR) was 95.4% and 95.6% for the training and validation sets, respectively, with MA ∆vki(sj) data. CONCLUSIONS: An information fusion perturbation theory and machine learning model for predicting warfarin blood levels was established. A model based on the RF algorithm could be used to predict the target international normalized ratio (INR), and a model based on the GDA algorithm could be used to predict the probability of being within the target INR range under different clinical scenarios.

Increasing GSH-Px Activity and Activating Wnt Pathway Promote Fine Wool Growth in FGF5-Edited Sheep.

Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4-20.0 µm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding.

Risk factors analysis and prediction model construction for severe pneumonia in older adult patients.

Objective: Pneumonia is a common and serious infectious disease that affects the older adult population. Severe pneumonia can lead to high mortality and morbidity in this group. Therefore, it is important to identify the risk factors and develop a prediction model for severe pneumonia in older adult patients. Method: In this study, we collected data from 1,000 older adult patients who were diagnosed with pneumonia and admitted to the intensive care unit (ICU) in a tertiary hospital. We used logistic regression and machine learning methods to analyze the risk factors and construct a prediction model for severe pneumonia in older adult patients. We evaluated the performance of the model using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and calibration plot. Result: We found that age, comorbidities, vital signs, laboratory tests, and radiological findings were associated with severe pneumonia in older adult patients. The prediction model had an accuracy of 0.85, a sensitivity of 0.80, a specificity of 0.88, and an AUC of 0.90. The calibration plot showed good agreement between the predicted and observed probabilities of severe pneumonia. Conclusion: The prediction model can help clinicians to stratify the risk of severe pneumonia in older adult patients and provide timely and appropriate interventions.

The Effectiveness and Safety of Intrapartum or Postpartum Catheterization in the Prevention of Postpartum Urinary Retention: A Scoping Review.

INTRODUCTION AND HYPOTHESIS: Catheterization is a common treatment for postpartum urinary retention (PUR); however, its application before diagnosis of PUR remains unclear. The aim was to give an overview of the existing literature on the effectiveness and safety of intrapartum or postpartum catheterization in the prevention of PUR. METHODS: This scoping review followed a methodological framework. PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, WanFang, the China Science and Technology Journal Database, and the China Biomedical Literature Database were searched from the inception of each database to 21 May 2023. RESULTS: The search revealed 16 studies examining three different catheterization methodologies, including 12 intrapartum studies. Ten studies concluded that intrapartum or postpartum catheterization prevented PUR, two of which were only for overt or covert PUR. In 4 out of 13 experimental studies, no significant difference was found: one for intrapartum catheterization versus routine nursing, the other for intrapartum or postpartum intermittent versus indwelling catheterization. However, one found that postpartum disposable catheterization after ineffective targeted care reduced the incidence of PUR compared with indwelling catheterization. One out of the 3 case-control studies concluded that prenatal catheterization ≥2 times was a risk factor for PUR. CONCLUSIONS: Based on the findings in this scoping review, catheterization prior to the diagnosis of PUR appears to play a role in preventing PUR and is safe. Preliminary evidence is accumulating on the effectiveness of three types of catheterization methods in preventing PUR, but more comprehensive studies are needed to establish these findings.

A new coumarin and a new flavonoid from Ochrocarpus longifolius.

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

Natural aromatic extract of black tea improved the water retention of pork meat batter.

The effect of varying proportions (w/w) of natural aromatic extract of black tea (NAEBT) with pre-emulsification on the water-holding capacity (WHC) of pork meat batter was investigated. The addition of NAEBT significantly reduced the cooking loss (CL) of pork meat batter from 23.95 % to 18.30 % (P < 0.05). Furthermore, NAEBT with pre-emulsification significantly improved the color stability and increased the springiness (P < 0.05). The results of TBARS and carbonyls indicated that NAEBT with pre-emulsification significantly alleviated oxidative damage to proteins (P < 0.05), resulting in an increased level of ß-sheet (P < 0.05), as confirmed by FT-IR analysis. As a result, the water mobility of pork meat batter was restricted (P < 0.05), resulting in an increase in the energy storage modulus (P < 0.05) and a decrease in the pore size. In summary, the WHC of pork meat batter was improved by the antioxidant effect of the NAEBT.

Spray drying the Pickering emulsions stabilized by chitosan/ovalbumin polyelectrolyte complexes for the production of oxidation stable tuna oil microcapsules.

The microencapsulation of polysaturated fatty acids by spray drying remains a challenge due to their susceptibility to oxidation. In this work, antioxidant Pickering emulsions were attempted as feeds to produce oxidation stable tuna oil microcapsules. The results indicated that the association between chitosan (CS) and ovalbumin (OVA) was a feasible way to fabricate antioxidant and wettable complexes and a high CS percentage favored these properties. The particles could yield tuna oil Pickering emulsions with enhanced oxidation stability through high-pressure homogenization, which were successfully spray dried to produce microcapsules with surface oil content of 8.84 % and microencapsulation efficiency of 76.65 %. The microcapsules exhibited significantly improved oxidation stability and their optimum peroxide values after storage at 50 °C, 85 % relative humidity, or natural light for 15 d were 48.67 %, 60.07 %, and 39.69 % respectively lower than the powder derived from the OVA-stabilized emulsion. Hence, Pickering emulsions stabilized by the CS/OVA polyelectrolyte complexes are potential in the production of oxidation stable polyunsaturated fatty acid microcapsules by spray drying.

Long-term spatial distribution and implication of black and brown carbon in the Tibetan Plateau.

Black carbon (BC) and brown carbon (BrC) over the high-altitude Tibetan Plateau (TP) can significantly influence regional and global climate change as well as glacial melting. However, obtaining plateau-scale in situ observations is challenging due to its high altitude. By integrating reanalysis data with on-site measurements, the spatial distribution of BC and BrC can be accurately estimated using the random forest algorithm (RF). In our study, the on-site observations of BC and BrC were successively conducted at four sites from 2018 to 2021. Ground-level BC and BrC concentrations were then obtained at a spatial resolution of 0.25° × 0.25° for three periods (including Periods-1980, 2000, and 2020) using RF and multi-source data. The highest annual concentrations of BC (1363.9 ± 338.7 ng/m3) and BrC (372.1 ± 96.2 ng/m3) were observed during Period-2000. BC contributed a dominant proportion of carbonaceous aerosol, with concentrations 3-4 times higher than those of BrC across the three periods. The ratios of BrC to BC decreased from Period-1980 to Period-2020, indicating the increasing importance of BC over the TP. Spatial distributions of plateau-scale BC and BrC concentrations showed heightened levels in the southeastern TP, particularly during Period-2000. These findings significantly enhance our understanding of the spatio-temporal distribution of light-absorbing carbonaceous aerosol over the TP.

Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

BACKGROUND: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. OBJECTIVE/METHODS: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. RESULTS: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. CONCLUSION: Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

Revealing the variances in color formation and bioactivities of seven catechin monomers throughout the enzymatic reaction by colorimetric and mass spectrometry.

The capacity differences of seven catechin monomers to produce colors after treating with catechin-free extract were investigated. After 240-min reaction, only (-)-epicatechin (EC) and (+)-catechin (C) presented obvious luminous red color with L* values of 63.32-71.73, a* values of 37.13-46.44, and b* values of 65.64-69.99. Meanwhile, the decrease rate of EC and C was 43.52 %-50.35 %, which were significantly lower than those of other catechin monomers (85.91 %-100 %). The oxidized products of catechin monomers were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with diode array detector, wherein dehydro-dimers and -trimers (oxidative coupling products of catechins' A-B ring) were found to be the major chromogenic compounds of EC and C. Additionally, the antioxidant capacity of catechin monomers only decreased after 30-min reaction, while along with further enzymatic reaction, catechin monomers presented comparable oxyradical scavenging ability (e.g., the DPPH inhibitory rates of catechin monomers were in the range of 24.42 %-50.77 %) to vitamin C (positive control, DPPH inhibitory rate was 27.66 %). Meanwhile, the inhibitory effects of most catechin monomers on α-glucosidase were enhanced in different degrees. These results provided basis for the development of enzymatically-oxidized catechin monomers as functional food color additives.

Global analysis of an age-structured tuberculosis model with an application to Jiangsu, China.

Diagnostic delay for TB infected individuals and the lack of TB vaccines for adults are the main challenges to achieve the goals of WHO by 2050. In order to evaluate the impacts of diagnostic delay and vaccination for adults on prevalence of TB, we propose an age-structured model with latent age and infection age, and we incorporate Mycobacterium TB in the environment and vaccination into the model. Diagnostic delay is indicated by the age of infection before receiving treatment. The threshold dynamics are established in terms of the basic reproduction number R 0 . When R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, which means that TB epidemic will die out; When R 0 = 1 , the disease-free equilibrium is globally attractive; there exists a unique endemic equilibrium and the endemic equilibrium is globally attractive when R 0 > 1 . We estimate that the basic reproduction number R 0 = 0.5320 (95% CI (0.3060, 0.7556)) in Jiangsu Province, which means that TB epidemic will die out. However, we find that the annual number of new TB cases by 2050 is 1,151 (95%CI: (138, 8,014)), which means that it is challenging to achieve the goal of WHO by 2050. To this end, we evaluate the possibility of achieving the goals of WHO if we start vaccinating adults and reduce diagnostic delay in 2025. Our results demonstrate that when the diagnostic delay is reduced from longer than four months to four months, or 20% adults are vaccinated, the goal of WHO in 2050 can be achieved, and 73,137 (95%CI: (23,906, 234,086)) and 54,828 (95%CI: (15,811, 206,468)) individuals will be prevented from being infected from 2025 to 2050, respectively. The modeling approaches and simulation results used in this work can help policymakers design control measures to reduce the prevalence of TB.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

BACKGROUND: Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS: The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS: The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS: CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn.

OBJECTIVE: Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. METHODS: We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. RESULTS: Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. CONCLUSIONS: Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.

The complete mitochondrial genome of cattle tick clade C reveals the genetic relationship within Rhipicephalus microplus complex.

Cattle ticks (Rhipicephalus microplus) are important economic ectoparasites causing direct and indirect damage to cattle and leading to severe economic losses in cattle husbandry. It is common knowledge that R. microplus is a species complex including five clades; however, the relationships within the R. microplus complex remain unresolved. In the present study, we assembled the complete mitochondrial genome of clade C by next-generation sequencing and proved its correctness based on long PCR amplification. It was 15,004 bp in length and consisted of 13 protein genes, 22 transfer genes, and two ribosomal genes located in the two strains. There were two copies of the repeat region (pseudo-nad1 and tRNA-Glu). Data revealed that cox1, cox2, and cox3 genes were conserved within R. microplus with small genetic differences. Ka/Ks ratios suggested that 12 protein genes (excluding nad6) may be neutral selection. The genetic and phylogenetic analyses indicated that clade C was greatly close to clade B. Findings in the current study provided more data for the identification and differentiation of the R. microplus complex and made up for the lack of information about R. microplus clade C.

Modelling the impact of human behavior using a two-layer Watts-Strogatz network for transmission and control of Mpox.

PURPOSE: This study aims to evaluate the effectiveness of mitigation strategies and analyze the impact of human behavior on the transmission of Mpox. The results can provide guidance to public health authorities on comprehensive prevention and control for the new Mpox virus strain in the Democratic Republic of Congo as of December 2023. METHODS: We develop a two-layer Watts-Strogatz network model. The basic reproduction number is calculated using the next-generation matrix approach. Markov chain Monte Carlo (MCMC) optimization algorithm is used to fit Mpox cases in Canada into the network model. Numerical simulations are used to assess the impact of mitigation strategies and human behavior on the final epidemic size. RESULTS: Our results show that the contact transmission rate of low-risk groups and susceptible humans increases when the contact transmission rate of high-risk groups and susceptible humans is controlled as the Mpox epidemic spreads. The contact transmission rate of high-risk groups after May 18, 2022, is approximately 20% lower than that before May 18, 2022. Our findings indicate a positive correlation between the basic reproduction number and the level of heterogeneity in human contacts, with the basic reproduction number estimated at 2.3475 (95% CI: 0.0749-6.9084). Reducing the average number of sexual contacts to two per week effectively reduces the reproduction number to below one. CONCLUSION: We need to pay attention to the re-emergence of the epidemics caused by low-risk groups when an outbreak dominated by high-risk groups is under control. Numerical simulations show that reducing the average number of sexual contacts to two per week is effective in slowing down the rapid spread of the epidemic. Our findings offer guidance for the public health authorities of the Democratic Republic of Congo in developing effective mitigation strategies.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.