Search

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Background Globally increasing atmospheric nitrogen (N) deposition has altered soil phosphorus (P) transformations and availability, and thereby influenced structure and function of terrestrial ecosystems. Edaphic characteristics and chemical form of deposited N could be important factors determining impacts of N deposition on soil P transformations, yet the underlying mechanisms remain largely unknown. Objectives of this study were to examine how mineral-N and amino N differently affect P fractions, and identify key soil properties determining N addition impacts on soil P transformations. Considering that amino N is an important component of deposited N and forest soils vary greatly in different regions, the results of present study can guide the management of forests across different soils under ongoing N deposition scenarios. Methods We conducted a 60-day laboratory experiment to investigate the effects of N addition (NH4NO3 and glycine) on soil P fractions and related biochemical properties in four representative forest soils (brown, yellow brown, aeolian sandy, and red soils) in China. Glycine and NH4NO3 were separately added at three rates (5, 10 and 20 g N m–2 yr–1). Results Firstly, the percent changes in organic P fractions with N addition were significantly greater than changes in inorganic P fractions across all soils. Secondly, the percent changes in P fractions with glycine and NH4NO3 additions were significantly correlated across all soils and treatments. However, glycine addition had significantly greater impacts on organic P fractions than NH4NO3 addition in the aeolian sandy and red soils with low organic carbon content. Thirdly, P fractions responded differently to N addition among the four soils. N-induced changes in microbial biomass and phosphatase activities, pH, exchangeable Ca2+ and Mg2+ contributed differently to the changes in P fractions with N addition in the four soils. Conclusions The different responses of P fractions to N addition in the four soils were mainly generated by the differences in extent of microbial N limitation, acid buffering capacity, and cation exchange capacity among the soils. The different impacts of mineral and amino N on soil P fractions can be ascribed to their divergent effects on soil pH, microbial biomass and activities.

Abstract Hexavalent chromium (Cr(VI)) is still a common contaminant in water. In this work, we studied the Cr(VI) adsorption by polyphenol-rich bacterial cellulose(BC) gel, synthesized by the Komagataeibacter rhaeticus K15 using wine pomace. The results showed that the equilibrium removal capacity was 473.09 ± 1.41 mg g−1 (dry weight). The quasi-second-order kinetics model and the Langmuir removal isotherm model was the most suitable for describing the Cr(VI) removal process. Toxic Cr(VI) was converted to the low toxic Cr(III) during the removal process via the reduction of Cr(VI) to Cr(III) by polyphenols released into the solution by the BC gel. The FTIR, XRD, XPS, SEM-EDX results indicated the physical adsorption on the surface of BC and the reduction reaction between polyphenol groups and Cr(VI) is the critical mechanism of Cr(VI) removal by BC. The finding of this study demonstrates that polyphenols-rich BC gel produced from wine pomace has a superior feature for future Cr(VI)-wastewater purification.

Objectives: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. Methods: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. Results: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. Conclusions: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

Abstract Background In the effort to prevent and control HIV/AIDS, China has established a national sentinel surveillance system. However, some sentinel sites face limitations in environmental resources and accessibility, prompting the exploration of alternative sample strategies. Dried plasma spots (DPS) samples are viewed as promising alternatives to traditional plasma samples due to their advantages, including sample stability, easy storage, and convenient transport. This study aims to develop a method for screening HIV, Treponema pallidum (TP), and Hepatitis C Virus (HCV) using DPS samples and assess their performance. Methods Based on existing commercial assay kits, a detection method was established through the optimization of experimental parameters, including the amount of plasma on filter paper, the volume of elution solution applied to dried plasma spots, the size of dried plasma spots, elution solution volume, elution solution components, elution temperature, and elution time. A series of laboratory evaluation panels were constructed for laboratory assessments, including the laboratory basic panel, laboratory interference panel, and laboratory precision panel. Additionally, clinical samples were used for evaluation. Results Optimal conditions for DPS sample extraction were: plasma volume, 100 µL; DPS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1‰ Tween20; elution time, 2 h; elution temperature, room temperature. A total of 619 paired plasma/DPS samples were tested by both methods. The DPS-based ELISA method exhibited 100% sensitivity/specificity for HIV, 98.6%/100% for TP, and 99.6%/100% for HCV. Kappa values between the plasma samples and DPS samples were 100% for HIV, 99% for TP, and 100% for HCV. The DPS-based ELISA method failed to detect 1 HCV mono-infected sample and TP in 1 HIV/HCV/TP co-infected sample. For the HIV/HCV/TP co-infected sample, the S/CO in the plasma sample was 2.143 and in the DPS sample was 0.5. For HCV, the S/CO (sample OD/cut-off) was 3.049 in the plasma sample and 0.878 in the DPS sample. Conclusions A single DPS, following one-time standardized processing, can be used to detect HIV, HCV, and TP. Researching and establishing laboratory testing methods better suited for China's sentinel surveillance have significant practical applications in improving HIV testing in resource-constrained environments.

BackgroundMembranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive.MethodsIn this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer.ResultsWe conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers.ConclusionThis evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P

Papilionoideae is the most species-rich subfamily of the third largest angiosperm family Fabaceae. One constituent large group, the inverted-repeat-lacking clade (IRLC), is well-known for the broad loss of one IR copy. Accumulating observations of massive plastomic disparities have made IRLC a well-suited model for exploring plastome evolution. However, there is still a large amount left to explore. The present study focused on the plastid tRNA (pttRNA) evolution within Papilionoideae, employing the currently densest sampling strategies for both the IRLC (156) and non-IRLC (109) lineages. Strikingly, our results revealed abundant inter-lineage variabilities in both tRNA sequences and structures, including a 3 nt difference in the average size of trnS-UGA, the consensus sequence disparities across 29 tRNAs, the distinct 3 nt indels in trnA-UGC, and an impressive 248 nt intron loss of IRLC trnI-GAU (potential markers). Additionally, there was unequal stability of the atypical secondary structures in trnS-GGA and trnS-UGA, as well as significantly diverse compositions of substitution events in all compared tRNAs (p < 0.05). Ultimately, these findings not only demonstrate the significant differences and unique markers of IRLC pttRNAs compared to other non-IRLC Papilionoideae, but also draw an important conclusion that the large losses of one IR potentially promote highly diverse evolutionary patterns of IRLC, which could partly compensate for the potential IR-lacking impacts.

In this study, the mitochondrial genome of Eulaelaps silvestris, which parasitizes Apodemus chevrieri, was sequenced and assembled to fill the gap in understanding the molecular evolution of the genus Eulaelaps. The E. silvestris mitochondrial genome is a double-stranded DNA molecule with a length of 14 882 bp, with a distinct AT preference for base composition and a notably higher AT content than GC content. The arrangement between genes is relatively compact, with a total of 10 gene intergenic regions and 12 gene overlap regions. All protein-coding genes had a typical ATN initiation codon, and only 2 protein-coding genes had an incomplete termination codon T. Out of the 13 protein-coding genes, the 5 most frequently used codons ended in A/U, with only 1 codon ending in G/C had an relative synonymous codon usage value >1. Except for trnS1 and trnS2, which lacked the D arm, all other tRNAs were able to form a typical cloverleaf structure; and there were a total of 38 mismatches in the folding process of tRNA genes. Unlike the gene arrangement order of the arthropod hypothetical ancestor, the E. silvestris mitochondrial genome underwent fewer rearrangements, mainly near tRNA genes and control regions. Both the maximum likelihood tree and the Bayesian tree showed that the family Haemogamasidae is most closely related to the family Dermanyssidae. The results not only provide a theoretical basis for studying the phylogenetic relationships of the genus Eulaelaps, but also provide molecular evidence that the family Haemogamasidae does not belong to the subfamily Laelapidae.

Abstract Background The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future.

Abstract Background Depression is a neuropsychiatric disease resulting from deteriorations of molecular networks and synaptic injury induced by stress. Traditional Chinese formula Xiaoyaosan (XYS) exert antidepressant effect, which was demonstrated by a great many of clinical and basic investigation. However, the exact mechanism of XYS has not yet been fully elucidated. Methods In this study, chronic unpredictable mild stress (CUMS) rats were used as a model of depression. Behavioral test and HE staining were used to detect the anti-depressant effects of XYS. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. The biological functions and potential mechanisms of XYS for depression were gathered from the GO and KEGG pathway. Then, constructed the competing endogenous RNA (ceRNA) networks to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Additionally, longest dendrite length, total length of dendrites, number of intersections, and density of dendritic spines were detected by Golgi staining. MAP2, PSD-95, SYN were detected by immunofluorescence respectively. BDNF, TrkB, p-TrkB, PI3K, Akt, p-Akt were measured by Western Blotting. Results The results showed that XYS could increase the locomotor activity and sugar preference, decreased swimming immobility time as well as attenuate hippocampal pathological damage. A total of 753 differentially expressed lncRNAs (DElncRNAs), 28 circRNAs (DEcircRNAs), 101 miRNAs (DEmiRNAs), and 477 mRNAs (DEmRNAs) were identified after the treatment of XYS in whole transcriptome sequencing analysis. Enrichment results revealed that XYS could regulate multiple aspects of depression through different synapse or synaptic associated signal, such as neurotrophin signaling and PI3K/Akt signaling pathways. Then, vivo experiments indicated that XYS could promote length, density, intersections of synapses and also increase the expression of MAP2 in hippocampal CA1, CA3 regions. Meanwhile, XYS could increase the expression of PSD-95, SYN in the CA1, CA3 regions of hippocampal by regulating the BDNF/trkB/PI3K signal axis. Conclusion The possible mechanism on synapse of XYS in depression was successfully predicted. BDNF/trkB/PI3K signal axis were the potential mechanism of XYS on synapse loss for its antidepressant. Collectively, our results provided novel information about the molecular basis of XYS in treating depression.

The yield of wheat in wheat–rice rotation cropping systems in the Yangtze River Plain, China, is adversely impacted by waterlogging. A raised bed planting (RBP) pattern may reduce waterlogging and increase the wheat yield after rice cultivation by improving the grain number per spike. However, the physiological basis for grain formation under RBP conditions remains poorly understood. The present study was performed over two growing seasons (2018/2019 and 2019/2020) to examine the effects of the planting pattern (i.e., RBP and flat planting (FP)) on the floret and grain formation features and leaf photosynthetic source characteristics of wheat. The results indicated that implementation of the RBP pattern improved the soil–plant nitrogen (N) supply during floret development, which facilitated balanced floret development, resulting in a 9.5% increase in the number of fertile florets per spike. Moreover, the RBP pattern delayed wheat leaf senescence and increased the photosynthetic source capacity by 13.9%, which produced more assimilates for grain filling. Delayed leaf senescence was attributed to the resultant high leaf N content and enhanced antioxidant metabolism. Correspondingly, under RBP conditions, 7.6–8.6% more grains per spike were recorded, and the grain yield was ultimately enhanced by 10.4–12.7%. These results demonstrate that the improvement of the spike differentiation process and the enhancement of the leaf photosynthetic capacity were the main reasons for the increased grain number per spike of wheat under the RBP pattern, and additional improvements in this technique should be achievable through further investigation.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 μg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1β, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

After drawing comparisons between the reaction pathways of cytochrome c oxidase (CcO, Complex 4) and the preceding complex cytochrome bc1 (Complex 3), both being proton pumping complexes along the electron transport chain, we provide an analysis of the reaction pathways in bacterial ba3 class CcO, comparing spectroscopic results and kinetics observations with results from DFT calculations. For an important arc of the catalytic cycle in CcO, we can trace the energy pathways for the chemical protons and show how these pathways drive proton pumping of the vectorial protons. We then explore the proton loading network above the Fe heme a3–CuB catalytic center, showing how protons are loaded in and then released by combining DFT-based reaction energies with molecular dynamics simulations over states of that cycle. We also propose some additional reaction pathways for the chemical and vector protons based on our recent work with spectroscopic support.