Leptin receptor Gln223Arg and Lys109Arg polymorphisms may be associated with HBV-related hepatocellular carcinoma risk: A system review and meta-analysis.

Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta-analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case-control researches consisting of 1323 cases and 1919 control cases were incorporated into meta-analysis. Researches indicated A-allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)-related HCC (mutant model, OR = 1.81, 95% CI = 1.36-2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32-1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV-related HCC (wild model, OR 0.59, 95%CI = 0.46-0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14-2.01, p = .005) as well as in those with HBV-related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49-3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23-2.26, p = .001). G-allele and AA genotype of rs1137101 might be in connection with boosted HBV-related HCC susceptibility, and wild-type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV-related HCC susceptibility. Such conclusions ought to be validated by larger and better-designed researches.

Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

Enrichment of SARS-CoV-2 sequence from nasopharyngeal swabs whilst identifying the nasal microbiome.

Simultaneously characterising the genomic information of coronaviruses and the underlying nasal microbiome from a single clinical sample would help characterise infection and disease. Metatranscriptomic approaches can be used to sequence SARS-CoV-2 (and other coronaviruses) and identify mRNAs associated with active transcription in the nasal microbiome. However, given the large sequence background, unenriched metatranscriptomic approaches often do not sequence SARS-CoV-2 to sufficient read and coverage depth to obtain a consensus genome, especially with moderate and low viral loads from clinical samples. In this study, various enrichment methods were assessed to detect SARS-CoV-2, identify lineages and define the nasal microbiome. The methods were underpinned by Oxford Nanopore long-read sequencing and variations of sequence independent single primer amplification (SISPA). The utility of the method(s) was also validated on samples from patients infected seasonal coronaviruses. The feasibility of profiling the nasal microbiome using these enrichment methods was explored. The findings shed light on the performance of different enrichment strategies and their applicability in characterising the composition of the nasal microbiome.

AST to ALT ratio as a prospective risk predictor for liver cirrhosis in patients with chronic HBV infection.

BACKGROUND: Serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR) is one of the most frequent indicators to discriminate fibrosis and cirrhosis. However, the results remained controversial. The aim of this study was to evaluate the predictive effect of AAR on hepatitis B virus (HBV)-related cirrhosis development. METHOD: A retrospective cohort study was conducted based on 1754 chronic HBV-infected patients. Clinical variables at their initial visit and follow-up data were collected. Cox proportional hazards model was constructed to evaluate the predictive value of AAR on cirrhosis risk, and its discrimination accuracy was determined by receiver operating characteristic (ROC). The time-dependent effect was assessed by a Fine and Gray competing risk model. RESULTS: Compared to patients with lower AAR, those with elevated AAR level had higher risk of cirrhosis development by adjusting for host characteristics (dichotomized analyses: hazard ratio = 2.77, P = 8.25 × 10 -4 ; tertile analyses: hazard ratio = 2.95, P = 1.61 × 10 -3 ), with an increasing risk trend ( Ptrend = 4.56 × 10 -4 ). The effect remained prominent when ALT or AST was abnormal, while no significant risk was observed when AST and ALT were simultaneously normal. Time-dependent effect analysis demonstrated a persistently higher risk, with the average hazard ratio equivalent to 1.92. AAR level could improve the discrimination efficacy of host variables with area under the curve increased from 0.684 to 0.711 ( P  =  0.039 ). CONCLUSION: Higher AAR was significantly associated with increased risk of HBV-related cirrhosis, and might be a potential predictor of cirrhosis development.

Preoperative albumin-alkaline phosphatase ratio affects the prognosis of patients undergoing hepatocellular carcinoma surgery.

BACKGROUND: The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. OBJECTIVE: This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. METHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. RESULTS: The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P< 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p= 0.036) and RFS (HR = 0.70, 95% CI 0.53-0.92, p= 0.011). CONCLUSIONS: The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment.

Heterointerface Design of Perovskite Single Crystals for High-Performance X-Ray Imaging.

Metal halide perovskite single crystals (MHP-SCs) are known for their facile fabrication into large sizes using inexpensive solution methods. Owing to their combination of large mobility-lifetime products and strong X-ray absorption, they are considered promising materials for efficient X-ray detection. However, they suffer from large dark currents and severe ion migration, which limit their sensitivity and stability in critical X-ray detection applications. Herein, a heterointerface design is proposed to reduce both the dark current and ion migration by forming a heterojunction. In addition, the carrier transport performance is significantly improved using heterointerface engineering by designing a gradient band structure in the SCs. The SC heterojunction detectors exhibit a high sensitivity of 3.98 × 105 µC Gyair -1 cm-2 with a low detection limit of 12.2 nGyair s-1 and a high spatial resolution of 10.2 lp mm-1 during imaging. These values are among the highest reported for state-of-the-art MHP X-ray detectors. Moreover, the detectors show excellent stability under continuous X-ray irradiation and maintainclear X-ray imaging after 240 d. This study provides novel insights into the design and fabrication of X-ray detectors with high detection efficiency and stability, which are beneficial for developing inexpensive, high-resolution X-ray imaging equipment.

Language inference-based learning for Low-Resource Chinese clinical named entity recognition using language model.

Electronic health records (EHRs) have been widely used and are gradually replacing paper records. Therefore, extracting valuable information from EHRs has become the focus and hotspot of current research. Clinical named entity recognition (CNER) is an important task in information extraction. Most current research methods used standard supervised learning approaches to fine-tune pre-trained language models (PLMs), which require a large amount of annotated data for model training. However, in realistic medical scenarios, annotated data are scarce, especially in the healthcare field. The process of annotating data in real clinical settings is time-consuming and labour-intensive. In this paper, a language inference-based learning method (LANGIL) is proposed to study clinical NER tasks with limited annotated samples, i.e., in low-resource clinical scenarios. A method based on prompt learning is designed to reformulate the entity recognition task into a language inference-based task. Differing from the standard fine-tuning method, the approach introduced in this paper does not design the additional network layers that train from scratch. This alleviates the gap between pre-training tasks and downstream tasks, allowing the comprehension capabilities of PLMs to be leveraged under the condition of limited training samples. The experiments on four Chinese clinical named entity recognition datasets showed that LANGIL achieves significant improvements in F1-score compared to the former method.

Synergistic Reinforcement of Si3N4 Based Ceramics Fabricated via Multiphase Strengthening under Low Temperature and Short Holding Time.

Si3N4 ceramic as a tool material shows promising application prospects in high-speed machining fields; however, the required high mechanical properties and low-cost preparation of Si3N4 ceramic tool materials restrict its application. Herein, synergistic reinforced Si3N4 ceramic tool materials were fabricated by adding ß-Si3N4 seeds, inexpensive Si3N4 whiskers and TiC particles into coarse commercial Si3N4 powder (D50 = 1.5 µm), then sintering by hot-pressing with low temperature and short holding time (1600 °C-30 min-40 MPa). The phase assemblage, microstructure evolution and toughening mechanisms were investigated. The results reveal that the sintered Si3N4 ceramics with synergistic reinforcement, compared to those with individual reinforcement, present an enhancement in relative density (from 94.92% to 97.15%), flexural strength (from 467.56 ± 36.48 to 809.10 ± 45.59 MPa), and fracture toughness (from 8.38 ± 0.19 to 10.67 ± 0.16 MPa·m1/2), as well as a fine Vickers hardness of 16.86 ± 0.19 GPa. Additionally, the various reinforcement modes of Si3N4 ceramics including intergranular fracture, crack deflection, crack bridging and whiskers extraction were observed in crack propagation, arising from the contributions of the added ß-Si3N4 seeds, Si3N4 whiskers and TiC particles. This work is expected to serve as a reference for the production of ceramic cutting tools.

Nitrogen Fixation by Benzene into Pyridine and Aniline in Water/Nitrogen Plasma.

We demonstrated direct conversion of benzene into pyridine and aniline, assisted through exact mass measurements (m/z 80.0494, 93.0574, and 94.0651, respectively), through the interaction of benzene with water/nitrogen vapor plasma produced by corona discharge. Systematic analysis using a series of isotopic standards indicated that formation of pyridine and aniline occurred through the reaction between neutral benzene and reactive N+(OH2)2 in water/nitrogen plasma; exact mass measurements of products and intermediates supported this hypothesis. As the proportion of water vapor in plasma increased over time, the reaction proceeded from exclusive formation of protonated pyridine to formation of protonated aniline as the main product; theoretical simulations indicated that the presence of water vapor promoted proton migration to elicit formation of protonated aniline. The reactions we discovered suggest a new mechanism for direct nitrogen fixation.

Analysis of SARS-CoV-2 Population Genetics from Samples Associated with Huanan Market and Early Cases Identifies Substitutions Associated with Future Variants of Concern.

SARS-CoV-2 began spreading through human-to-human transmission first within China and then worldwide, with increasing sequence diversity associated with time and the further spread of the virus. The spillover events in the Huanan market were associated with two lineages of SARS-CoV-2 (lineages A and B). Infecting virus populations and those in infected individuals consist of a dominant genomic sequence and minor genomic variants; these latter populations can indicate sites on the genome that may be subject to mutational changes-either neutral or advantageous sites and those that act as a reservoir for future dominant variants-when placed under selection pressure. The earliest deposited sequences with human infections associated with the Huanan market shared very close homology with each other and were all lineage B. However, there were minor genomic variants present in each sample that encompassed synonymous and non-synonymous changes. Fusion sequences characteristic of defective RNA were identified that could potentially link transmission chains between individuals. Although all the individuals appeared to have lineage B as the dominant sequence, nucleotides associated with lineage A could be found at very low frequencies. Several substitutions (but not deletions) associated with much later variants of concern (VoCs) were already present as minor genomic variants. This suggests that low-frequency substitutions at the start of a pandemic could be a reservoir of future dominant variants and/or provide information on potential sites within the genome associated with future plasticity.

Altered brain networks and connections in chronic heart failure patients complicated with cognitive impairment.

Objective: Accumulating evidence shows that cognitive impairment (CI) in chronic heart failure (CHF) patients is related to brain network dysfunction. This study investigated brain network structure and rich-club organization in chronic heart failure patients with cognitive impairment based on graph analysis of diffusion tensor imaging data. Methods: The brain structure networks of 30 CHF patients without CI and 30 CHF patients with CI were constructed. Using graph theory analysis and rich-club analysis, changes in global and local characteristics of the subjects' brain network and rich-club organization were quantitatively calculated, and the correlation with cognitive function was analyzed. Results: Compared to the CHF patients in the group without CI group, the CHF patients in the group with CI group had lower global efficiency, local efficiency, clustering coefficient, the small-world attribute, and increased shortest path length. The CHF patients with CI group showed lower nodal degree centrality in the fusiform gyrus on the right (FFG.R) and nodal efficiency in the orbital superior frontal gyrus on the left (ORB sup. L), the orbital inferior frontal gyrus on the left (ORB inf. L), and the posterior cingulate gyrus on the right (PCG.R) compared with CHF patients without CI group. The CHF patients with CI group showed a smaller fiber number of edges in specific regions. In CHF patients with CI, global efficiency, local efficiency and the connected edge of the orbital superior frontal gyrus on the right (ORB sup. R) to the orbital middle frontal gyrus on the right (ORB mid. R) were positively correlated with Visuospatial/Executive function. The connected edge of the orbital superior frontal gyrus on the right to the orbital inferior frontal gyrus on the right (ORB inf. R) is positively correlated to attention/calculation. Compared with the CHF patients without CI group, the connection strength of feeder connection and local connection in CHF patients with CI group was significantly reduced, although the strength of rich-club connection in CHF patients complicated with CI group was decreased compared with the control, there was no statistical difference. In addition, the rich-club connection strength was related to the orientation (direction force) of the Montreal cognitive assessment (MoCA) scale, and the feeder and local connection strength was related to Visuospatial/Executive function of MoCA scale in the CHF patients with CI. Conclusion: Chronic heart failure patients with CI exhibited lower global and local brain network properties, reduced white matter fiber connectivity, as well as a decreased strength in local and feeder connections in key brain regions. The disrupted brain network characteristics and connectivity was associated with cognitive impairment in CHF patients. Our findings suggest that impaired brain network properties and decreased connectivity, a feature of progressive disruption of brain networks, predict the development of cognitive impairment in patients with chronic heart failure.

Sex Differences in the Impact of Metabolic Dysfunction-associated Fatty Liver Disease on the of Patients with Hepatocellular Carcinoma After Radical Resection.

Background: International experts have put forward a new definition for metabolic dysfunction-associated fatty liver disease (MAFLD). Nonetheless, sex differences in MAFLD function in hepatocellular carcinoma (HCC) survival is still unknown. Therefore, the current work focused on exploring the gender-specific association of MAFLD effect on prognosis after radical resection of liver cancer. Methods: The long-term prognostic outcomes of 642 HCC patients undergoing hepatectomy were analyzed retrospectively. To calculate overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier (KM) curve was plotted. Further, using Cox proportional model to explore the prognostic factors. Sensitivity analysis was performed using propensity score matching (PSM) to balance the confounding bias. Results: For MAFLD patients, median OS and RFS times were 6.8 years and 6.1 years, respectively, compared to 8.5 years and 2.9 years in non-MAFLD patients. KM curve shown that compare with non-MAFLD patients, MAFLD patients had a higher survival rate in men, but had a lower survival rate in women (P<0.05). Multivariate analysis showed that MAFLD was significantly risk factor with mortality in the female (HR = 5.177, 95%CI: 1.475-18.193). However, MAFLD was not related to RFS This correlation was consistent after PSM analysis. Conclusions: MAFLD can improve the mortality of women undergoing radical resection for liver cancer, which independently estimate disease prognosis but is not related to recurrence-free survival.

Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients.

BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

Brain diffusion tensor imaging reveals altered connections and networks in epilepsy patients.

Introduction: Accumulating evidence shows that epilepsy is a disease caused by brain network dysfunction. This study explored changes in brain network structure in epilepsy patients based on graph analysis of diffusion tensor imaging data. Methods: The brain structure networks of 42 healthy control individuals and 26 epilepsy patients were constructed. Using graph theory analysis, global and local network topology parameters of the brain structure network were calculated, and changes in global and local characteristics of the brain network in epilepsy patients were quantitatively analyzed. Results: Compared with the healthy control group, the epilepsy patient group showed lower global efficiency, local efficiency, clustering coefficient, and a longer shortest path length. Both healthy control individuals and epilepsy patients showed small-world attributes, with no significant difference between groups. The epilepsy patient group showed lower nodal local efficiency and nodal clustering coefficient in the right olfactory cortex and right rectus and lower nodal degree centrality in the right olfactory cortex and the left paracentral lobular compared with the healthy control group. In addition, the epilepsy patient group showed a smaller fiber number of edges in specific regions of the frontal lobe, temporal lobe, and default mode network, indicating reduced connection strength. Discussion: Epilepsy patients exhibited lower global and local brain network properties as well as reduced white matter fiber connectivity in key brain regions. These findings further support the idea that epilepsy is a brain network disorder.

Linked Mutations in the Ebola Virus Polymerase Are Associated with Organ Specific Phenotypes.

Ebola virus (EBOV) causes a severe infection called Ebola virus disease (EVD). The pathogenesis of EBOV infection is complex, and outcome has been associated with a variety of immunological and cellular factors. Disease can result from several mechanisms, including direct organ and endothelial cell damage as a result of viral replication. During the2013 to 2016 Western Africa EBOV outbreak, several mutants emerged, with changes in the genes of nucleoprotein (NP), glycoprotein (GP), and the large (L) protein. Reverse genetic analysis has been used to investigate whether these mutations played any role in pathogenesis with mixed results depending on the experimental system used. Previous studies investigated the impact of three single nonsynonymous mutations (GP-A82V, NP-R111C, and L-D759G) on the fatality rate of mouse and ferret models and suggested that the L-D759G mutation decreased the virulence of EBOV. In this study, the effect of these three mutations was further evaluated by deep sequencing to determine viral population genetics and the host response in longitudinal samples of blood, liver, kidney, spleen, and lung tissues taken from the previous ferret model. The data indicated that the mutations were maintained in the different tissues, but the frequency of minor genomic mutations were different. In addition, compared to wild-type virus, the recombinant mutants had different within host effects, where the D759G (and accompanying Q986H) substitution in the L protein resulted in an upregulation of the immune response in the kidney, liver, spleen, and lungs. Together these studies provide insights into the biology of EBOV mutants both between and within hosts. IMPORTANCE Ebola virus infection can have dramatic effects on the human body which manifest in Ebola virus disease. The outcome of infection is either survival or death and in the former group with the potential of longer-term health consequences and persistent infection. Disease severity is undoubtedly associated with the host response, often with overt inflammatory responses correlated with poorer outcomes. The scale of the2013 to 2016 Western African Ebola virus outbreak revealed new aspects of viral biology. This included the emergence of mutants with potentially altered virulence. Biobanked tissue from ferret models of EBOV infected with different mutants that emerged in the Western Africa outbreak was used to investigate the effect of EBOV genomic variation in different tissues. Overall, the work provided insights into the population genetics of EBOV and showed that different organs in an animal model can respond differently to variants of EBOV.

Discovering layered lead-free perovskite solar absorbers via cation transmutation.

For the exploration of stable lead-free perovskites for solar cell applications, we propose a series of Dion-Jacobson (DJ) double perovskites with the formula BDA2MIMIIIX8 (BDA = 1,4-butanediamine) by substituting two Pb2+ in BDAPbI4 with an MI+ (Na+, K+, Rb+, Cu+, Ag+, and Au+) and MIII3+ (Bi3+, In3+, and Sb3+) pair. First-principles calculations demonstrated the thermal stabilities of all the proposed BDA2MIMIIIX8 perovskites. The electronic properties of BDA2MIMIIIX8 depend strongly on the choice of MI+ + MIII3+ and the structural archetype, and three out of 54 candidates with suitable solar band gaps and superior optoelectronic properties were selected for photovoltaic application. A highest theoretical maximal efficiency of over 31.6% is predicted for BDA2AuBiI8. The DJ-structure-induced interlayer interaction of apical I-I atoms is found to play a crucial role in promoting the optoelectronic performance of the selected candidates. This study provides a new concept for designing lead-free perovskites for efficient solar cells.

The relationship between metabolic dysfunction-associated fatty liver disease and the incidence rate of extrahepatic cancer.

Background: The associations between metabolic dysfunction-associated fatty liver disease (MAFLD) and cancer development, especially extrahepatic cancers, are unknown. The aims of the current study were to investigate the cancer incidence rates of MAFLD and analyze the associations between MAFLD and the development of cancers. Methods: This historical cohort study included participants who underwent ultrasonographic detection of hepatic steatosis at a tertiary hospital in China from January 2013 to October 2021. MAFLD was diagnosed in accordance with The International Expert Consensus Statement. Cox proportional hazards regression modeling was used to assess the associations between MAFLD and the development of cancers. Results: Of the 47,801 participants, 16,093 (33.7%) had MAFLD. During the total follow-up of 175,137 person-years (median 3.3 years), the cancer incidence rate in the MAFLD group was higher than that in the non-MAFLD group [473.5 vs. 255.1 per 100,000 person-years; incidence rate ratio 1.86; 95% confidence interval (CI) 1.57-2.19]. After adjustment for age, gender, smoking status, and alcohol status, MAFLD was moderately associated with cancers of the female reproductive system/organs (labium, uterus, cervix, and ovary) [hazard ratio (HR) 2.24; 95% CI 1.09-4.60], thyroid (HR 3.64; 95% CI 1.82-7.30), and bladder (HR 4.19; 95% CI 1.15-15.27) in the total study cohort. Conclusion: MAFLD was associated with the development of cancers of the female reproductive system/organs (labium, uterus, cervix, and ovary), thyroid, and bladder in the total study cohort.

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection.

BACKGROUND: The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. RESULTS: Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. CONCLUSIONS: These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.

Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency. Methods: The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated. Results: A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04-1.67, P = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96-2.10, P = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09-1.87, P = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01-2.57, P = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09-1.79, P = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models. Conclusion: Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.

Interlayer-Spacing Engineering of Lead-Free Perovskite Single Crystal for High-Performance X-Ray Imaging.

Lead-free A3 Bi2 I9 -type perovskites are demonstrated as a class of promising semiconductors for high-performance X-ray detection due to their high bulk resistivity and strong X-ray absorption, as well as reduced ion migration. However, due to their long interlamellar distance along their c-axis, their limited carrier transport along the vertical direction is a bottleneck for their detection sensitivity. Herein, a new A-site cation of aminoguanidinium (AG) with all-NH2 terminals is designed to shorten the interlayer spacing by forming more and stronger NH···I hydrogen bonds. The prepared large AG3 Bi2 I9 single crystals (SCs) render shorter interlamellar distance for a larger mobility-lifetime product of 7.94 × 10-3  cm2  V-1 , which is three times higher than the value measured on the best MA3 Bi2 I9 SC (2.87 × 10-3  cm2  V-1 ). Therefore, the X-ray detectors fabricated on the AG3 Bi2 I9 SC exhibit high sensitivity of 5791 uC Gy-1  cm-2 , a low detection limit of 2.6 nGy s-1, and a short response time of 690 µs, all of which are far better than those of the state-of-the-art MA3 Bi2 I9 SC detectors. The combination of high sensitivity and high stability enables astonishingly high spatial resolution (8.7 lp mm-1 ) X-ray imaging. This work will facilitate the development of low-cost and high-performance lead-free X-ray detectors.