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In this paper, the original RSEI model (including greenness index, humidity index, heat index and dryness index) and their contribution rate (%) are used to evaluate the change of ecological environment. To study how natural and anthropogenic changes in ecological environment affect ecosystem function and how these factors interact, CASA model was used to estimate the correlation between the net primary productivity of vegetation (NPP), population density and land use. This could reveal the influence factors of ecological environment change in the Wanjiang River Basin from 2000 to 2022. The results show that the combing RSEI and CASA models can effectively show the spatial-temporal variation and spatial distribution of NPP of vegetation in Wanjiang Basin. During this period, RSEI of the basin showed an overall upward trend, and the RSEI increased by about 0.1/10 a. The vegetation productivity in most areas was gradually improved, the ecological environment was restored, and the ecological environment quality was gradually improved. The average annual NPP simulated by CASA was 266.81 g C·m-2·a-1. The variation trend of NPP in vegetation showed a slight decrease, but the overall NPP level was basically unchanged. There is a significant correlation between NPP and population density, a negative correlation between NPP and population density areas such as city centers, and a positive correlation between NPP and population density in areas with frequent agricultural activities. From 2010 to 2020, there is a significant positive correlation between population density and land use.

BackgroundPatients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients.MethodsThe 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed.ResultsCompared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively.ConclusionOur study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity.

BackgroundThe systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL.MethodsThis cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed.ResultsA total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes.ConclusionOur findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL.

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3–6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3–4–6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0–13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review.

BackgroundThe lower limb motor dysfunction caused by stroke is one of the main sequelae affecting patients’ ability to live normally in the later period. Acupuncture treatment of limb movement dysfunction after stroke has been recommended by authoritative guidelines for reducing limb spasticity, enhancing limb strength and so on. However, the efficacy of different acupuncture methods in treating lower limb motor dysfunction after stroke remains controversial.ObjectiveIn this paper, network meta-analysis (NMA) was used to prioritize various acupuncture intervention combinations commonly used in clinical practice, try to screen the acupuncture intervention scheme with the highest clinical efficacy and safety, and explore its rationality in guiding clinical practice.MethodsWe searched a total of 4,312 studies from 8 databases and 2 clinical trial registries, and selected 43 articles for systematic review. We used pairwise meta-analysis and network meta-analysis to evaluate the efficacy and ranking of various acupuncture interventions. At the same time, the risk of bias, publication bias, and sensitivity of included randomized controlled trials were analyzed. The main outcome indicator was Fugl-Meyer assessment of lower extremity (FMA-LE), and the secondary outcome indicators were Modified Barthel Index (MBI), Berg balance scale (BBS) and Modified Ashworth scale (MAS).ResultsA total of 4,134 patients in 43 studies were included. The intervention included 9 acupuncture-related treatments, of which 20.9% were classified as high-risk. Among the four outcome indicators in pairwise meta-analysis, the effect of body acupuncture combined with conventional rehabilitation has the highest comprehensive credibility in terms of efficacy and safety comparing with conventional rehabilitation [SMD = 1.14, 95%CI (0.81, 1.46)], [SMD = 1.35, 95%CI (0.97, 1.72)], [SMD = 1.22, 95%CI (0.39, 2.05)], [SMD = 1.21, 95%CI (0.74, 1.44)]. In addition, multiple intervention methods, for example, warm acupuncture plus rehabilitation treatment for MBI and electroacupuncture plus body acupuncture plus rehabilitation treatment for BBS, may increase certain additional effects on different outcome indicators.ConclusionThis study proves that body acupuncture combined with rehabilitation treatment is the most widely used intervention method with the highest evidence quality in the treatment of lower limb motor dysfunction after stroke. However, for some other acupuncture methods, large samples and high-quality clinical randomized controlled trials are still needed to be fully verified.

BackgroundSystemic lupus erythematosus (SLE) is frequently accompanied by various complications, with cardiovascular diseases being particularly concerning due to their high mortality rate. Although there is clinical evidence suggesting a potential correlation between SLE and heart failure (HF), the underlying shared mechanism is not fully understood. Therefore, it is imperative to explore the potential mechanisms and shared therapeutic targets between SLE and HF.MethodsThe SLE and HF datasets were downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) in both SLE and HF were performed using “limma” R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) analyses were conducted to analyze the enriched functions and pathways of DEGs in both SLE and HF datasets. Protein–Protein Interaction network (PPI) and the molecular complex detection (MCODE) plugins in the Cytoscape software were performed to identify the shared hub genes between SLE and HF datasets. R package “limma” was utilized to validate the expression of hub genes based on SLE (GSE122459) and HF (GSE196656) datasets. CIBERSORT algorithm was utilized to analyze the immune cell infiltration of SLE and HF samples based on SLE (GSE112087) and HF (GSE116250) datasets. A weighted gene co-expression network analysis (WGCNA) network was established to further validate the hub genes based on HF dataset (GSE116250). Molecular biology techniques were conducted to validate the hub genes.Results999 shared DGEs were identified between SLE and HF datasets, which were mainly enriched in pathways related to Th17 cell differentiation. 5 shared hub genes among the common DGEs between SLE and HF datasets were screened and validated, including HSP90AB1, NEDD8, RPLP0, UBB, and UBC. Additionally, 5 hub genes were identified in the central part of the MEbrown module, showing the strongest correlation with dilated cardiomyopathy. HSP90AB1 and UBC were upregulated in failing hearts compared to non-failing hearts, while UBB, NEDD8, and RPLP0 did not show significant changes.ConclusionHSP90AB1 and UBC are closely related to the co-pathogenesis of SLE and HF mediated by immune cell infiltration. They serve as promising molecular markers and potential therapeutic targets for the treatment of SLE combined with HF.

IntroductionThe finding that familiarity can support associative memory by unitizing the to -be-learned items into a novel representation has been widely accepted, but its effects on overall performance of associative memory and recollection are still controversial.MethodsThe current study aims to elucidate these discrepancies by identifying potential moderating factors through a combined approach of meta-analysis and behavioral experiment.ResultsResults consistently showed that changes in the level of unitization and age groups were two important moderators. Specifically, unitization enhanced younger and older adults’ associative memory and its supporting processes (i.e., familiarity and recollection) when the level of unitization between studied and rearranged pairs was changed. However, when this level remained constant, unitization exhibited no impact on associative memory and familiarity in younger adults, but showed an enhanced effect in older adults. Furthermore, results revealed a marked group difference between younger and older adults in associative memory when the unitization level of noncompound words remained unaltered. Upon breaking this condition, the group difference was reduced by enhancing familiarity or recollection.DiscussionThese findings not only clarify some of the inconsistencies in the literature concerning the impact of unitization on associative memory, but also suggest that unitization is a beneficial strategy for reducing group difference in associative memory, with its effectiveness varying according to the level of unitization changes.

Chromate [Cr(VI)] is a highly toxic heavy metal element, representing one of the most prevalent sources of wastewater contamination. It poses a significant threat to human health and food safety. Therefore, effective treatment before discharging wastewater is of paramount importance. In this study, termite nests (Coptotermes formosanus and Odontotermes formosanus), as natural biomass materials, were used to adsorb Cr(VI) ions in wastewater as a strategy to reduce environmental pollution and minimize poisoning by Cr. Structural and morphological characterizations were performed using scanning electron microscope (SEM), Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) analyses. Batch adsorption experiments were conducted to evaluate the influence of termite nest dosage, coexisting ions, and pH. To gain further insight, detailed studies on adsorption kinetics, adsorption isotherms, and adsorption thermodynamics were undertaken. The results indicate that under acidic pH conditions, both termite nests exhibit the highest adsorption capacity for Cr(VI), with an optimal adsorbent dosage of 10 g/L. The maximum adsorption capacities of C. formosanus nest and O. formosanus nest for Cr(VI) were found to be 48.52 mg/g and 35.99 mg/g, respectively. Thermodynamic studies confirmed the spontaneous and endothermic nature of the adsorption process. In the rapeseed cultivation experiment, the growth status of Brassica chinensis L. post-adsorption treatment was markedly improved compared to the untreated group. Additionally, the concentration of Cr(VI) in the plants was significantly reduced. This demonstrates both the inhibitory effect of Cr(VI) on the growth of oilseed rape and the effectiveness of water remediation techniques. In addition, both types of termite nests can be effectively reused by 0.1 mol/L HCl. To the best of our knowledge, this is the first report of adsorption removal of Cr(VI) by C. formosanus nest and O. formosanus nest. Compared to traditional natural biomass adsorbents, termite nests exhibit a relatively higher adsorption capacity for Cr(VI). The results of this study demonstrate that subterranean termite nests can efficiently remove Cr(VI) from wastewater, offering the potential for a cost-effective and reusable bioremediation agent with the advantages of ease of operation.

The main olfactory bulb is the key element of the olfactory pathway of rodents. To precisely dissect the neural pathway in the main olfactory bulb (MOB), it is necessary to construct the three-dimensional morphologies of the anatomical structures within it with micro-level resolution. However, the construction remains challenging due to the complicated shape of the anatomical structures in the main olfactory bulb and the high resolution of micro-optical images. To address these issues, we propose an interactive volume image segmentation method with micro-level resolution in the horizontal and axial direction. Firstly, we obtain the initial location of the anatomical structures by manual annotation and design a patch-based neural network to learn the complex texture feature of the anatomical structures. Then we randomly sample some patches to predict by the trained network and perform an annotation reconstruction based on intensity calculation to get the final location results of the anatomical structures. Our experiments were conducted using Nissl-stained brain images acquired by the Micro-optical sectioning tomography (MOST) system. Our method achieved a mean dice similarity coefficient (DSC) of 81.8% and obtain the best segmentation performance. At the same time, the experiment shows the three-dimensional morphology reconstruction results of the anatomical structures in the main olfactory bulb are smooth and consistent with their natural shapes, which addresses the possibility of constructing three-dimensional morphologies of the anatomical structures in the whole brain.

Meat procurement strategies, displaying a great variety world-widely, are ideal for examining how geography and culture shape the subsistence. We collate zooarchaeological data from 26 Neolithic and Bronze Age sites/locales in the Guanzhong region (Shaanxi Province, China), a key region of early Chinese civilization, to demonstrate the changing process of meat procurement and its associations with environmental, demographic and societal factors. Comparing the proportion of the domesticates versus wild animals, along with the proportion of the domesticated pigs versus bovids (i.e., sheep, goat, and cattle), we summarize three characteristics of the meat procurement strategy at Guanzhong. Firstly, the changing pattern of meat procurement did not follow a linear progression of shifting subsistence from hunting to husbandry, albeit involving acceleration and regression from the pre-Yangshao period to the Western Zhou dynasty. Secondly, contrasting meat procurement strategies might have been employed between central settlements and lower-ranking settlements. Thirdly, an increasing importance of domesticated bovids was evident during the pre-Zhou and Western Zhou periods. We therefore argue population size and societal form might have shaped meat procurement strategies, in addition to natural environments. Subsistence, in turn, also lays the economic foundation for social development. It was not until the pre-Zhou and Western Zhou periods, when a more stable meat procurement strategy involving utilizing a variety of the domesticates was pervasively employed in this region, that Guanzhong had gradually gained its prominence in Chinese civilization.

ObjectiveThe combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.MethodsWe performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all‐grade (grade 1‐5) and high‐grade (grade 3‐5) immune-related adverse events (irAEs). Secondary outcomes were all‐grade (grade 1‐5) and high‐grade (grade 3‐5) irAEs of subgroups of ICIs.ResultsThere were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.ConclusionNab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.

Mycoplasma pneumoniae is a common causative pathogen of community-acquired pneumonia. An accurate and sensitive detection method is important for evaluating disease severity and treatment efficacy. Digital droplet PCR (ddPCR) is a competent method enabling the absolute quantification of DNA copy number with high precision and sensitivity. We established ddPCR for M. pneumoniae detection, using clinical specimens for validation, and this showed excellent specificity for M. pneumoniae. The limit of detection of ddPCR was 2.9 copies/reaction, while that for real-time PCR was 10.8 copies/reaction. In total, 178 clinical samples were used to evaluate the ddPCR assay, which correctly identified and differentiated 80 positive samples, whereas the real-time PCR tested 79 samples as positive. One sample that tested negative in real-time PCR was positive in ddPCR, with a bacterial load of three copies/test. For samples that tested positive in both methods, the cycle threshold of real-time PCR was highly correlated with the copy number of ddPCR. Bacterial loads in patients with severe M. pneumoniae pneumonia were significantly higher than those in patients with general M. pneumoniae pneumonia. The ddPCR showed that bacterial loads were significantly decreased after macrolide treatment, which could have reflected the treatment efficacy. The proposed ddPCR assay was sensitive and specific for the detection of M. pneumoniae. Quantitative monitoring of bacterial load in clinical samples could help clinicians to evaluate treatment efficacy.

BackgroundChlamydia psittaci is a small bacterium often found in birds, including poultry, and domesticated mammals, which causes psittacosis (or parrot fever) in humans. Different strains of C. psittaci respond variably to antibiotics, suggesting a possible risk of antibiotic resistance. In general, different genotypes of C. psittaci have relatively stable hosts and different pathogenicity.MethodsMacrogenomic sequencing was performed using nucleic acids extracted from psittacosis patients’ alveolar lavage fluid samples and analyzed for genetic variability and antibiotic resistance genes. Nucleic acid amplification sequences specific to the core coding region of the C. psittaci ompA gene were used, and a phylogenetic tree was constructed with C. psittaci genotypic sequences from other sources, including Chinese published sources. The C. psittaci found in each patient were genotyped by comparing ompA gene sequences. In addition, to better illustrate the relationship between genotype and host of C. psittaci, 60 bird fecal samples were collected from bird-selling stores for screening and C. psittaci typing.ResultsMacrogenomic sequence alignment revealed the presence of resistance genes in varying abundance in samples from all three patients, including C. psittaci resistance gene sequences from two patients that matched those previously published on NCBI. Based on ompA genotyping, two patients were infected with C. psittaci genotype A and one patient was infected with genotype B. All five C. psittaci-positive samples obtained from bird-selling stores were genotype A. Both genotypes are reported to be infectious to humans. The host origin of the samples and the previously reported main sources of each genotype suggested that all but one of the C. psittaci genotype A in this study were derived from parrots, while genotype B was probably derived from chickens.ConclusionThe presence of bacterial resistance genes in psittacosis patients may affect the efficacy of clinical antibiotic therapy. Focusing on the developmental progression of bacterial resistance genes and differences in the therapeutic efficacy may facilitate effective treatment of clinical bacterial infections. Pathogenicity genotypes (e.g., genotype A and genotype B) are not limited to one animal host, suggesting that monitoring the development and changes of C. psittaci may help prevent transmission to humans.

Nudix hydrolases comprise a large and ubiquitous protein superfamily that catalyzes the hydrolysis of a nucleoside diphosphate linked to another moiety X (Nudix). Sulfolobus acidocaldarius possesses four Nudix domain-containing proteins (SACI_RS00730/Saci_0153, SACI_RS02625/Saci_0550, SACI_RS00060/Saci_0013/Saci_NudT5, and SACI_RS00575/Saci_0121). Deletion strains were generated for the four individual Nudix genes and for both Nudix genes annotated to encode ADP-ribose pyrophosphatases (SACI_RS00730, SACI_RS00060) and did not reveal a distinct phenotype compared to the wild-type strain under standard growth conditions, nutrient stress or heat stress conditions. We employed RNA-seq to establish the transcriptome profiles of the Nudix deletion strains, revealing a large number of differentially regulated genes, most notably in the ΔSACI_RS00730/SACI_RS00060 double knock-out strain and the ΔSACI_RS00575 single deletion strain. The absence of Nudix hydrolases is suggested to impact transcription via differentially regulated transcriptional regulators. We observed downregulation of the lysine biosynthesis and the archaellum formation iModulons in stationary phase cells, as well as upregulation of two genes involved in the de novo NAD+ biosynthesis pathway. Furthermore, the deletion strains exhibited upregulation of two thermosome subunits (α, β) and the toxin-antitoxin system VapBC, which are implicated in the archaeal heat shock response. These results uncover a defined set of pathways that involve archaeal Nudix protein activities and assist in their functional characterization.

ObjectiveThe aim of this study is to compare the efficacy and safety of complete multi-level vs. iliac-only revascularization for the treatment of concomitant iliac and superficial femoral artery (SFA) occlusive disease.MethodsA total of 139 consecutive adult patients with severe stenosis and occlusive iliac and SFA disease with Rutherford categories 2–5 underwent multi-level (n = 71) and iliac-only (n = 68) revascularization at the Department of Intervention Vascular Surgery, Peking University Third Hospital, and Aerospace Center Hospital, between March 2015 and June 2017. Improvement in Rutherford class, perioperative major adverse events, the length of stay, survival rate, and limb salvage rate were assessed. The neutrophil–lymphocyte ratio and platelet–lymphocyte ratio were compared between the two groups.ResultsAt 48 months, improvement in the Rutherford category was observed in the two groups with no significant difference (P = 0.809). Additionally, the two groups were similar concerning the primary patency (84.0% vs. 79.1%, P = 0.717) and limb salvage rate (93.1% vs. 91.3%, P = 0.781). A higher proportion of the perioperative major adverse events (33.8% vs. 27.9%, P = 0.455), the all-cause mortality (11.3% vs. 8.8%, P = 0.632), and the average length of hospital stay [7.0 (6.0, 11.0) vs. 7.0 (5.0, 8.0), P = 0.037] were seen in the multi-level group compared with the iliac-only group.ConclusionFor concomitant iliac and superficial femoral artery occlusive disease, iliac-only revascularization has favorable efficacy and safety outcomes compared with complete multi-level revascularization in selected patients with patent profunda femoris artery and at least one healthy outflow tract of the infrapopliteal artery.

Underwater noise pollution from the world’s longest cross-sea bridge—the Hong Kong-Zhuhai-Macao Bridge (HZMB)—which stretches across the Chinese White Dolphin National Nature Reserve (of the People’s Republic of China, PRC) in the Pearl River Estuary may affect the distribution of local humpback dolphins. In this study, static passive acoustic monitoring was applied to monitor biosonar activity of humpback dolphins and underwater noise adjacent to the tunnel section of the HZMB for more than one year. During the monitoring period, dolphin biosonar signals were detected on 88.5% of days. A significant temporal pattern occurred in dolphin biosonar activity and in anthropogenic noise. Biosonar activity was significantly higher at night than during the day, whereas underwater noise occurred more in the day than at night. Significantly more echolocation signals were detected in winter-spring than in summer-autumn, and highest acoustic activity occurred significantly more during high tide than at other tidal periods. In addition, the negative correlation between elevated underwater noise and dolphin sonar activity in winter suggests that dolphins may avoid noisy waters for short periods, perhaps due to auditory stress, but fish prey movement cannot be ruled out. These findings facilitate understanding activity patterns of humpback dolphins in the Pearl River Estuary and may contribute to conservation efforts.

BackgroundRecent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers.MethodsWe used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration.ResultsSignificant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78–0.98; P = 0.02). The specific cancer types that exhibited significant correlation between VCI and OS included breast cancer (AHR = 0.14; 95% CI = 0.05–0.40; P < 0.01), head and neck squamous cell carcinoma (AHR = 0.20; 95% CI = 0.07–0.59; P < 0.01), kidney clear cell carcinoma (AHR = 0.66; 95% CI = 0.48–0.92; P = 0.01), and rectum adenocarcinoma (AHR = 0.01; 95% CI = 0.001–0.38; P = 0.02). Interestingly, VCI was correlated with altered immunotypes and associated with TMB and MSI negatively in colon and rectal adenocarcinoma (P < 0.001) but positively in lung squamous cell carcinoma (P < 0.05). In vivo study using mice bearing colon cancer xenografts demonstrated that vitamin C could inhibit tumor growth with significant impact on immune cell infiltration.ConclusionVCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.

BackgroundPrevious investigations have reported that controlling nutritional (CONUT) status scores, incorporating total cholesterol (TC) and serum albumin (SA) values, and total lymphocyte (LY) counts, are reliable malignant tumor predictors. However, CONUT scores for predicting endometrial cancer (EC) remain unexplored.ObjectiveTo evaluate preoperative CONUT scores as prognostic factors for postoperative EC.MethodsWe retrospectively evaluated preoperative CONUT scores in 785 surgically resected EC patients at our hospital between June 2012 and May 2016. Using time-dependent receiver operating characteristic (ROC) analyses, patients were split into: 1) CONUT-high (CH) (≥1) and 2) CONUT-low (CL) (

ObjectiveThe study aimed to investigate the differences in clinical features between pediatric and adult patients with first-episode MOG-IgG associated disorders (MOGAD) and evaluate the relationship between the fibrinogen-to-albumin ratio (FAR) and the severity of neurological deficits at disease onset.MethodsWe retrospectively collected and analyzed biochemical test results, imaging characteristics, clinical manifestations, expanded disability status scale (EDSS) score, and FAR. The Spearman correlation analysis and logistic regression models were used to examine the association between FAR and severity. Receiver operating characteristic (ROC) curve analysis was to analyze the predictive ability of FAR for the severity of neurological deficits.ResultsFever (50.0%), headache (36.1%), and blurred vision (27.8%) were the most common clinical manifestations in the pediatric group (

Black truffles and white truffles are widely studied around the world, but their effects on plant growth and physiological responses, and on the mycorrhizosphere bacterial community of the host plant remain unclear. Here, mycorrhizal colonization of Castanopsis rockii by Tuber indicum (Chinese black truffle) and T. lijiangense (Chinese white truffle), respectively, was induced in a greenhouse study, and their effects on host growth, physiological responses and mycorrhizosphere bacterial communities were compared. The results show that colonization of both Tuber species significantly increased leaf photosynthetic rate, leaf P concentration and mycorrhizosphere acid phosphatase activity, as well as richness of mycorrhizosphere bacterial communities of C. rockii seedlings. However, T. indicum colonization on the one hand significantly decreased tartrate content, bacterial acid phosphatase, phoC gene abundance in the mycorrhizosphere, and peroxidase (POD) activity of ectomycorrhizal root tips, but on the other hand increased mycorrhizosphere pH and superoxide dismutase (SOD) of ectomycorrhizal root tips, compared to T. lijiangense colonization. Moreover, principal coordinate and β-diversity analyses show significant differences in mycorrhizosphere bacterial community composition between T. indicum and T. lijiangese colonized C. rockii seedlings. Finally, the relative abundance of the bacterium Agromyces cerinus significantly correlated to mycorrhizosphere acid phosphatase activity and leaf P concentration, suggesting that this bacterium might play an important role in P mobilization and acquisition. Overall, these results suggest that T. indicum and T. lijiangense differently regulate their host plant’s physiological responses and mycorrhizosphere bacterial community.

ObjectivesThe shoulder-hand syndrome (SHS) severely impedes the function recovery process of patients after stroke. It is incapable to identify the factors at high risk for its occurrence, and there is no effective treatment. This study intends to apply the random forest (RF) algorithm in ensemble learning to establish a predictive model for the occurrence of SHS after stroke, aiming to identify high-risk SHS in the first-stroke onset population and discuss possible therapeutic methods.MethodsWe retrospectively studied all the first-onset stroke patients with one-side hemiplegia, then 36 patients that met the criteria were included. The patients’ data concerning a wide spectrum of demographic, clinical, and laboratory data were analyzed. RF algorithms were built to predict the SHS occurrence, and the model’s reliability was measured with a confusion matrix and the area under the receiver operating curves (ROC).ResultsA binary classification model was trained based on 25 handpicked features. The area under the ROC curve of the prediction model was 0.8 and the out-of-bag accuracy rate was 72.73%. The confusion matrix indicated a sensitivity of 0.8 and a specificity of 0.5, respectively. And the feature importance scored the weights (top 3 from large to small) in the classification were D-dimer, C-reactive protein, and hemoglobin.ConclusionA reliable predictive model can be established based on post-stroke patients’ demographic, clinical, and laboratory data. Combining the results of RF and traditional statistical methods, our model found that D-dimer, CRP, and hemoglobin affected the occurrence of the SHS after stroke in a relatively small sample of data with tightly controlled inclusion criteria.

Ischemic stroke has been a prominent focus of scientific investigation owing to its high prevalence, complex pathogenesis, and difficulties in treatment. Mitochondria play an important role in cellular energy homeostasis and are involved in neuronal death following ischemic stroke. Hence, maintaining mitochondrial function is critical for neuronal survival and neurological improvement in ischemic stroke, and mitochondria are key therapeutic targets in cerebral stroke research. With the benefits of high efficacy, low cost, and high safety, traditional Chinese medicine (TCM) has great advantages in preventing and treating ischemic stroke. Accumulating studies have explored the effect of TCM in preventing and treating ischemic stroke from the perspective of regulating mitochondrial structure and function. In this review, we discuss the molecular mechanisms by which mitochondria are involved in ischemic stroke. Furthermore, we summarized the current advances in TCM in preventing and treating ischemic stroke by modulating mitochondria. We aimed to provide a new perspective and enlightenment for TCM in the prevention and treatment of ischemic stroke by modulating mitochondria.

BackgroundSocial deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear.MethodsA total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P < 0.01, and cluster-level P < 0.05).ResultsThe clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects.ConclusionThe present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.

ObjectiveFurther studies are needed to improve the understanding of the pathological process underlying cognitive impairments. The purpose of this study is to investigate the global and topographic changes of white matter integrity and cortical structure related to cognitive impairments in a community-based population.MethodsA cross-sectional analysis was performed based on 995 subjects (aged 56.8 ± 9.1 years, 34.8% males) from the Shunyi study, a community-dwelling cohort. Cognitive status was accessed by a series of neurocognitive tests including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), category Verbal Fluency Test (VFT), Digit Span Test (DST), and Trail Making Tests A and B (TMT-A and TMT-B). Structural and diffusional MRI data were acquired. White matter integrity was assessed using fractional anisotropy (FA), mean diffusivity (MD), and peak width of skeletonized mean diffusivity (PSMD). Cortical surface area, thickness, and volume were measured using Freesurfer. Probabilistic tractography was further conducted to track the white matter fibers connecting to the cortical regions related to cognition. General linear models were used to investigate the association between brain structure and cognition.ResultsGlobal mean FA and MD were significantly associated with performances in VFT (FA, β 0.119, p

IntroductionThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world’s health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients.MethodsWe downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways.ResultsBy analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations.DiscussionIn conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD.

Staphylococcus aureus is an opportunistic pathogen that shows a unique ability to quickly respond to a variety of antibiotics. The Crp/Fnr family transcriptional regulator ArcR controls expression of arginine deiminase pathway genes arcABDC, which enable the utilization of arginine as an energy source for cell growth under anaerobic conditions. However, ArcR shares low overall similarity with other Crp/Fnr family proteins, suggesting that they differ in the response to environmental stress. In this study, MIC and survival assays were performed to determine the role of ArcR in antibiotic resistance and tolerance. The results showed that deletion of arcR reduced tolerance of S.aureus to fluoroquinolone antibiotics, mainly through a defect in the response to oxidative stress. In ΔarcR mutant, the expression of the major catalase gene katA was downregulated, and katA overexpression restored bacterial resistance to oxidative stress and antibiotics. We showed that ArcR directly regulated katA transcription by binding to the promoter region of katA. Therefore, our results revealed the contribution of ArcR in bacterial tolerance to oxidative stress and subsequently to fluoroquinolones antibiotics. This study added our understanding on the role of Crp/Fnr family in bacterial susceptibility to antibiotics.

A recent, unprecedented outbreak of human mpox virus infection has led to cases in non-African nations, and the number of confirmed or suspected cases outside of Africa has exceeded 1,000 within 5 weeks. Mpox may pose a double threat to public health in the context of the ongoing COVID-19 pandemic. It is difficult to distinguish mpox virus infection from other diseases in the early stages, and patients are contagious from the onset of nonspecific symptoms; therefore, it is crucial to develop rapid and specific diagnostic methods. The diagnosis of mpox relies on real-time polymerase chain reaction, a time-consuming method that requires a highly sophisticated thermal cycler, which makes it unsuitable for widespread use in underdeveloped areas, where the outbreak is still severe. In this study, we developed a recombinase-aided amplification (RAA) assay that can detect mpox virus within 5–10 minutes. The conserved regions of the A27L gene and F3L gene were selected as targets, as they amplify well from different mpox virus clades with no cross-reaction from other pathogens. The sensitivity of this RAA assay is 10 copies/reaction for the A27L gene and 102 copies/reaction for the F3L gene. When applied to simulated clinical samples, both targets showed 100% specificity, and the detection limits were consistent with the sensitivity results. Moreover, through clinical blinded sample detection, RAA exhibits the same detection power as RT-PCR. In summary, the RAA mpox assay described here exhibits rapid detection, high sensitivity and specificity, and low operational difficulty, making it suitable for mpox virus detection in less developed countries and regions.

The transition period is the stage of the high incidence of metabolic and infectious diseases in dairy cows. Improving transition dairy cows’ health is crucial for the industry. This study aimed to determine the effects of dietary supplementation medium-chain fatty acids (MCFAs) on immune function, metabolic status, performance of transition dairy cows. Twenty multiparous Holstein cows randomly assigned to two treatments at 35 d before calving. 1) CON (fed the basal 2) MCFA treatment (basal diet was supplemented at an additional 20 g MCFAs mixture every day) until 70 d after calving. The results showed that the serum amyloid A myeloperoxidase concentrations in the blood of cows in MCFA treatment significantly decreased during the early lactation (from 1 d to 28 d after calving) 0.03, 0.04, respectively) compared with the CON, while the tumor necrosis factor concentration was significantly decreased at 56 d after calving (P = 0.02). In addition, the concentration of insulin in the pre-calving (from 21 d before calving to calving) blood of cows in MCFA treatment was significantly decreased (P = 0.04), and concentration of triglyceride also showed a downward trend at 28 d after calving 0.07). Meanwhile, MCFAs supplementation significantly decreased the concentrations of lithocholic acid, hyodeoxycholic acid, and hyocholic acid in the blood at 1 d calving (P = 0.02, < 0.01, < 0.01, respectively), and the level of hyocholic acid taurocholic acid concentrations (P < 0.01, = 0.01, respectively) decreased dramatically at 14 d after calving. However, compared with the CON, the pre-calving dry matter intake and the early lactation milk yield in MCFA treatment were significantly decreased (P = 0.05, 0.02, respectively). In conclusion, MCFAs supplementation transition diet could improve the immune function and metabolic status of dairy cows, and the health of transition cows might be beneficial from the endocrine status.

Lake littoral zones with abundant submerged vegetation are considered to harbor diverse biotic communities and additionally serve as spawning grounds for important fishery resources. In recent decades, due to various human activities submerged vegetation in lakes have declined dramatically resulting in the function loss of spawning grounds. In order to enhance the recruitment of lacustrine fish (mainly Carassius auratus and Cyprinus carpio) and the proliferation of fishery resources, we explored a method of constructing artificial spawning ground based on artificial spawning substrate in lake. The results of present study indicate that the artificial substrates with complex and dense three-dimensional structure which have enough space to enable material exchange and oxygen circulation could be efficient to enhance fish recruitment. The water temperature of spawning peaks of artificial substrates were within the range of 20 ~ 25°C, and the water temperature provides a basis for the deployment period of artificial spawning grounds. The spawning substrate in the upper layer of water column was more attractive for fish to spawn. The above results provide guidance for the deployment of artificial spawning grounds from both temporal and spatial scales. Observations on the behavior of aggregations found that spawning activities mainly occurred at night and in the early morning. The abundance of larger individuals (>20 cm), as potential spawning groups, increased during this period. The above findings are informative to the construction and management of artificial spawning ground in lakes.

ObjectiveTo identify trends in the prevalence of mild cognitive impairment (MCI) and dementia, and to determine risk factors associated with the early detection of dementia among U.S. middle-aged and older adults.MethodsWe used 10-year nationally representative longitudinal data from the Health and Retirement Study (HRS) (2006–2016). Adults aged 55 years or older were included to examine the trend. To identify the associated factors, adults aged 55 years or older in 2006 who developed MCI or dementia in subsequent waves until the 2016 wave were included. Early and late detection of dementia were identified using the Langa-Weir classification of cognitive function. Multivariate logistic regression models were used to identify factors associated with the early detection of dementia.ResultsThe sample size for the analysis of the prevalence of MCI and dementia ranged from 14,935 to 16,115 in the six survey years, and 3,729 individuals were identified to determine associated factors of the early detection of dementia. Among them, participants aged 65 years or older accounted for 77.9%, and male participants accounted for 37.2%. The 10-year prevalence of MCI and dementia was 14.5 and 6.6%, respectively. We also found decreasing prevalence trends in MCI (from 14.9 to 13.6%) and dementia (from 7.4 to 6.0%) overall in the past decade. Using logistic regression controlling for the year, non-Hispanic black (MCI: OR = 2.83, P < 0.001; dementia: OR = 2.53, P < 0.001) and Hispanic (MCI: OR = 2.52, P < 0.001; dementia: OR = 2.62, P < 0.001) had a higher prevalence of both MCI and dementia than non-Hispanic white participants. In addition, men had a lower prevalence of MCI (OR = 0.94, P = 0.035) and dementia (OR = 0.84, P < 0.001) compared to women. Associated factors of the early detection of dementia include age, gender, race, educational attainment, stroke, arthritis diseases, heart problems, and pensions.ConclusionThis study found a decreasing trend in the prevalence of MCI and dementia in the past decade and associated racial/ethnic and gender disparities among U.S. middle-aged and older adults. Healthcare policies and strategies may be needed to address health disparities in the prevalence and take the associated factors of the early detection of dementia into account in clinical settings.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological disease of unknown etiology, and most patients with PERM are positive for anti-glycine receptor (GlyR) antibody. In this case study, we report a clinical case of a varicella-zoster virus-infected patient who developed anti-GlyR antibody-positive PERM. He initially suffered from herpes zoster and gradually developed symptoms of impaired brainstem functions including hoarse voice and dysphagia, accompanied by paroxysmal sympathetic hyperactivity. The patient also suffered from severe spasms, which were easily triggered by external stimuli. Glycine receptor antibodies were then found to be positive in serum and cerebrospinal fluid, and the diagnosis of PERM was confirmed. Methylprednisolone and gamma globulin treatments were given, and spasms were improved after treatment. Unfortunately, the patient's family insisted on automatic discharge and the patient passed away several days later.

Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our study, and the mouse models had osteoporosis based on the phenotype and methylation levels in the mouse’s bone. Furthermore, the methylation level of the OVX mice was significantly changed compared to that of SHAM mice. Therefore, we performed genome-level analysis on the mouse model using transcriptome and Whole Genome Bisulfite Sequencing (WGBS) by combining the data of two omics and discovered that the changes in gene expression level caused by osteoporosis primarily focused on the decrease of bone and muscle development and the activation of the immune system. According to intersection analysis of methylation and transcriptome data, the differentially expressed genes and pathways are consistent with the differentially expressed methylation locations and regions. Further, the differentially expressed methylation sites were mainly concentrated in promoters, exons, and other critical functional regions of essential differentially expressed genes. This is also the primary cause of gene differential expression variations, indicating that estrogen deficiency might regulate gene expression by altering methylation modification, leading to osteoporosis. We demonstrated the clinical value of methylation modification research, and these findings would improve the current understanding of underlying molecular mechanisms of osteoporosis incidence and development and provide new ideas for early detection and treatment of osteoporosis.

Inverted light-sheet microscopy (ILSM) is widely employed for fast large-volume imaging of biological tissue. However, the scattering especially in an uncleared sample, and the divergent propagation of the illumination beam lead to a trade-off between axial resolution and imaging depth. Herein, we propose naturally modulated ILSM (NM-ILSM) as a technique to improve axial resolution while simultaneously maintaining the wide field-of-view (FOV), and enhancing imaging contrast via background suppression. Theoretical derivations, simulations, and experimental imaging demonstrate 15% axial resolution increases, and fivefold greater image contrast compared with conventional ILSM. Therefore, NM-ILSM allows convenient imaging quality improvement for uncleared tissue and could extend the biological application scope of ILSM.

Acute kidney injury (AKI) is a complex and common set of multifactorial clinical syndromes, and associated with increased in-hospital mortality. There is increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with the development of a variety of kidney diseases, including AKI. However, the pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of creatinine and more severe renal tubule injury after cisplatin injection. We found that HHcy aggravated renal mitochondrial damage, mainly manifested as decreased ATP β, significantly increased cytoplasmic Cyt C expression and the ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 reduced Hcy-induced mitochondrial damage, thereby reducing the level of apoptosis. In conclusion, these results suggest that HHcy might aggravate the development of AKI by increasing mitochondrial damage and that reducing Hcy levels or inhibiting mitochondrial damage may be a potential therapeutic strategy to delay the development of AKI.

Visualizing the relationships and interactions among different biological components in the whole brain is crucial to our understanding of brain structures and functions. However, an automatic multicolor whole-brain imaging technique is still lacking. Here, we developed a multicolor wide-field large-volume tomography (multicolor WVT) to simultaneously acquire fluorescent signals in blue, green, and red channels in the whole brain. To facilitate the segmentation of brain regions and anatomical annotation, we used 4′, 6-diamidino-2-phenylindole (DAPI) to provide cytoarchitecture through real-time counterstaining. We optimized the imaging planes and modes of three channels to overcome the axial chromatic aberration of the illumination path and avoid the crosstalk from DAPI to the green channel without the modification of system configuration. We also developed an automatic contour recognition algorithm based on DAPI-staining cytoarchitecture to shorten data acquisition time and reduce data redundancy. To demonstrate the potential of our system in deciphering the relationship of the multiple components of neural circuits, we acquired and quantified the brain-wide distributions of cholinergic neurons and input of ventral Caudoputamen (CP) with the anatomical annotation in the same brain. We further identified the cholinergic type of upstream neurons projecting to CP through the triple-color collocated analysis and quantified its proportions in the two brain-wide distributions. Both accounted for 0.22%, implying CP might be modulated by non-cholinergic neurons. Our method provides a new research tool for studying the different biological components in the same organ and potentially facilitates the understanding of the processing mechanism of neural circuits and other biological activities.

A newly excavated ritual site, Xuechi, exposed abundant sacrificial livestock, allowing to understand the supplies and managements of livestock during the early Chinese Qin-Han Empires. Here we reported animal enamel 87Sr/86Sr values from the Xuechi site that are obviously higher than those of local snails and surface water, as well as calcites of the Chinese Loess Plateau (CLP) where the site was located, strongly suggesting that these sacrificial animals were not raised in the vicinity of the site. The regional bioavailable 87Sr/86Sr isoscape further indicates that some livestock were probably derived more than one hundred kilometers away, suggesting a complex social network for recruiting and managing the sacrificial activities. In the context of other Neolithic-Bronze Age records on the CLP, an increasing trend in variation of faunal 87Sr/86Sr values shows a robust correlation to Chinese states’ trajectory, in concordance with the territorial expansion model for state formation.

BackgroundConcomitant intrahepatic ectopic thyroid is rare in patients with hepatocellular carcinoma. Thyroid follicular structures outside the hepatocellular carcinoma lesions are regarded as satellite nodules or intrahepatic metastases of hepatocellular carcinoma, which often leads to misdiagnosis and overtreatment of hepatocellular carcinoma patients.Case presentationWe report the case of an 83-year-old man with moderately differentiated hepatocellular carcinoma (2.5 cm) whose liver contained ectopic thyroid tissue. An encapsulated, multinodular grayish-yellow mass and multiple satellite nodules were detected and removed by right hepatic lobectomy. Microscopically, the main tumor displayed a predominant trabecular, cord-like structure. Liver tissue 0.5 cm from the tumor had a benign-appearing follicular thyroid structure. The follicles contained colloid tissue and were lined with low cuboidal cells with scant cytoplasm; lymphatic tissue was also present in the area. The hepatocellular carcinoma cells were positive for hepatocyte antigen and glypican-3 and negative for cytokeratin 19. The follicular thyroid cells expressed thyroglobulin, PAX8, and thyroid transcription factor-1. A metastatic thyroid neoplasm was excluded clinically and by ultrasound and computed tomography. One month after surgery, all of the patient's serological markers were normal; no tumor recurrence or metastasis has been detected for 7 postoperative months.ConclusionsThe finding of ectopic thyroid tissue in the liver of a patient with hepatocellular carcinoma is very rare. The possibility of hepatocellular carcinoma forming satellite nodules and intrahepatic metastasis should be ruled out first and immunohistochemistry may be definitive in making the diagnosis. Further examination is needed to exclude thyroid cancer liver metastases.

Colon cancer (CC) is a multistage disease and one of the most common cancers worldwide. Establishing an effective treatment strategies of early colon cancer is of great significance for preventing its development and reducing mortality. The occurrence of colon cancer is closely related to changes in the intestinal flora structure. Therefore, remodelling the intestinal flora structure through prebiotics is a powerful approach for preventing and treating the occurrence and development of colon cancer. Isomaltooligosaccharides (IMOs) are often found in fermented foods and can directly reach the gut for use by microorganisms. In this study, a rat model of early colon cancer (DMH) was established by subcutaneous injection of 1,2-dimethylhydrazine, and the model rats were fed IMOs as a dietary intervention (DI). The untargeted faecal metabolomics, gut metabolome and intestinal function of the model rats were investigated. The results showed that DMH, DI and IMOs alone (IMOs) groups exhibited gut microbial community changes. In the DI group, there was an increased abundance of probiotics (Lactobacillus) and decreased abundance of CC marker bacteria (Fusobacterium). The key variations in the faecal metabolites of the DI group included decreased levels of glucose, bile acids (including deoxycholic acid and chenodeoxycholic acid) and amino acids (including L-glutamic acid and L-alanine). In addition, dietary intake of IMOs attenuated the intestinal inflammatory response, improved the intestinal microecological environment, and slowed the development of DMH-induced early CC in rats. This work provides a theoretical basis and technical support for the clinical prevention or treatment of CC with prebiotics.

The Burkholderia cepacia complex (BCC) is a group of opportunistic pathogens, including Burkholderia cepacia, Burkholderia multivorans, Burkholderia vietnamiensis and Burkholderia ambifaria, which can cause severe respiratory tract infections and lead to high mortality rates among humans. The early diagnosis and effective treatment of BCC infection are therefore crucial. In this study, a novel and rapid recombinase-aided amplification (RAA) assay targeting the 16S rRNA gene was developed for BCC detection. The protocol for this RAA assay could be completed in 10 min at 39°C, with a sensitivity of 10 copies per reaction and no cross-reactivity with other pathogens. To characterize the effectiveness of the RAA assay, we further collected 269 clinical samples from patients with bacterial pneumonia. The sensitivity and specificity of the RAA assay were 100% and 98.5%, respectively. Seven BCC-infected patients were detected using the RAA assay, and three BCC strains were isolated from the 269 clinical samples. Our data showed that the prevalence of BCC infection was 2.60%, which is higher than the 1.40% reported in previous studies, suggesting that high sensitivity is vital to BCC detection. We also screened a patient with B. vietnamiensis infection using the RAA assay in clinic, allowing for appropriate treatment to be initiated rapidly. Together, these data indicate that the RAA assay targeting the 16S rRNA gene can be applied for the early and rapid detection of BCC pathogens in patients with an uncharacterized infection who are immunocompromised or have underlying diseases, thereby providing guidance for effective treatment.

Background: Inappropriate medication use is common around the world, particularly among older patients, and, despite potentially being preventable, often leads to adverse clinical and economic outcomes. However, there is a dearth of information regarding this prominent issue in China.Objectives: To evaluate the extent to which the physician can correctly identify potentially inappropriate medication (PIM) in older patients and to understand physicians’ attitudes towards improving PIM knowledge.Methods: An online, cross-sectional survey was conducted anonymously among practicing physicians in China from November through December 2020. Knowledge of PIM was accessed using seven clinical vignettes covering a wide variety of therapeutic areas. Source of information and perceived barriers regarding PIM were also evaluated. We performed the ordinary least square regression analysis to understand the potential factors related to physicians’ knowledge of PIM.Results: A total of 597 study participants were included in the analysis. More than half of them had never heard of any screening tool for PIMs (n = 328, 54.9%) and the most frequently acknowledged tool was the China PIM Criteria (n = 259, 43.4%). For the seven clinical vignettes testing physicians’ knowledge on the medications that should be generally avoided in older patients, the mean score was 2.91 points out of 7 (SD: 1.32), with the median score of three points (IQR: 2–4). Only one-third of the respondents were feeling confident when prescribing for older patients (n = 255, 35.08%). Package inserts have been used as the major source of PIM information (always, n = 177, 29.65%; frequently, n = 286, 47.91%). Perceived barriers to appropriate prescribing include polypharmacy (n = 460, 77.05%), lack of formal education on prescribing for the older patients (n = 428, 71.69%).Conclusion: In this online survey evaluating physicians’ ability to detect PIM for older patients, approximately 40% of PIM were recognized, suggesting an insufficient level of knowledge about appropriate prescribing.

Obtaining various structures of the entire mature heart at single-cell resolution is highly desired in cardiac studies; however, effective methodologies are still lacking. Here, we propose a pipeline for labeling and imaging myocardial and vascular structures. In this pipeline, the myocardium is counterstained using fluorescent dyes and the cardiovasculature is labeled using transgenic markers. High-definition dual-color fluorescence micro-optical sectioning tomography is used to perform heart-wide tissue imaging, enabling the acquisition of whole-heart data at a voxel resolution of 0.32 × 0.32 × 1 μm3. Obtained structural data demonstrated the superiority of the pipeline. In particular, the three-dimensional morphology and spatial arrangement of reconstructed cardiomyocytes were revealed, and high-resolution vascular data helped determine differences in the features of endothelial cells and complex coiled capillaries. Our pipeline can be used in cardiac studies for examining the structures of the entire heart at the single-cell level.

The dynamic assembly of SKP1•CUL1•F-box protein (SCF) ubiquitin ligases is important for protein ubiquitination and degradation. This process is enabled by CAND1, which exchanges F-box proteins associated with the common CUL1 scaffold, and thereby, recycles the limited CUL1 core and allows diverse F-box proteins to assemble active SCFs. Previous human cell biological and computational studies have led to the adaptive exchange hypothesis, which suggests that the CAND1-mediated exchange confers plasticity on the SCF system, allowing cells to tolerate large variations in F-box protein expression. Here, we tested this hypothesis using Arabidopsis thaliana, a multicellular organism expressing hundreds of F-box protein genes at variable levels in different tissues. The cand1 null mutant in Arabidopsis is viable but produce almost no seeds. Bioinformatic, cell biological, and developmental analyses revealed that the low fertility in the cand1 mutant is associated with cell death in pollen, where the net expression of F-box protein genes is significantly higher than any other Arabidopsis tissue. In addition, we show that the transmission efficiency of the cand1 null allele was reduced through the male but not the female gametophyte. Our results suggest that CAND1 activity is essential in cells or tissues expressing high levels of F-box proteins. This finding is consistent with the proposed adaptive exchange hypothesis, demonstrating the necessity of the evolutionarily conserved CAND1-mediated exchange system in the development of a multicellular organism.

Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p

Molecular assays on nasopharyngeal swabs act as a confirmatory test in coronavirus disease (COVID-19) diagnosis. However, the technical requirements of nasopharyngeal sampling and molecular assays limit the testing capabilities. Recent studies suggest the use of saliva for the COVID-19 diagnostic test. In this study, 44 patients diagnosed with COVID-19 in The Third People’s Hospital of Shenzhen were enrolled. Saliva and serum specimens were obtained at different time points and the immunoglobulins against SARS-CoV-2 were measured. The results showed that saliva IgA presented a higher COI value than IgG and IgM. In matched saliva and serum samples, all saliva samples presented lower IgG levels than serum samples, and only one saliva sample presented a higher IgM level. The conversion rates of saliva IgA and the detection of viral nucleic acids were analyzed in the first and second weeks after hospitalization. The positive rates increased when combining saliva IgA and viral nucleic acid detection. In conclusion, our results provide evidence that saliva IgA could serve as a useful index for the early diagnosis of COVID-19.

Introduction: Although persistent inhibition of HBV replication by antiviral therapy has shown to slow disease progression, cost-related access barriers to these essential medicines are becoming salient. The national volume-based procurement (NVBP) was piloted in China and led to substantial reduction in the list price of prescription drugs. To examine the impact of NVBP on selected antiviral medication costs per defined daily dose (DDD), procurement volumes, and spending.Methods: We employed an interrupted time series design to examine changes in cost per defined daily dose (DDD), procurement volumes, and spending for NVBP bid-winning antiviral medications (tenofovir disoproxil fumarate and entecavir) in 11 pilot cities from 2017 to 2020. Procurement transaction data were obtained from 9,454 hospitals in the Chinese Hospital Pharmaceutical Audit (CHPA) database. In the secondary analysis, the control group comprised two non-NVBP drugs (adefovir and lamivudine) procured in 11 cities not exposed to the NVBP.Results: Cost per DDD of the two hepatitis B virus (HBV) antiviral medications reduced by CNY1.598 (p = 0.002) immediately following the implementation of NVBP, dropping from an average cost of CNY16.483 per DDD at baseline to CNY6.420 at the end of the observation period. NVBP implementation resulted in a substantial reduction in daily costs of antivirals and an increase in monthly procurement volumes by 6.674 million DDDs (p = 0.017), while monthly spending was reduced by CNY138.26 million (p = 0.002). In the secondary ITS analysis with a control group, the average cost per DDD of the NVBP bid-winning antivirals declined by CNY4.537 (p < 0.001), monthly procurement volumes increased by 7.209 million DDDs (p = 0.002), and monthly spending dropped by CNY138.83 million (p < 0.001).Conclusion: Volume-based procurement piloted in China may be effective for reducing price and total expenditures and improving drug utilization, which is especially important for HBV patients who need constant access to antiviral therapies.

AimsThis study aimed to observe the efficacy and safety of anlotinib in the treatment of small cell lung cancer (SCLC) in the real world, as first-line maintenance therapy, second-line, and above.MethodsClinical data of 109 patients with SCLC treated with anlotinib and hospitalized at The First Affiliated Hospital of Zhengzhou University from June 2018 to June 2020 were retrospectively analyzed. Analysis of short-term efficacy and survival was performed, with p

Background: The rapid worldwide spread of the Omicron variant of SARS-CoV-2 has unleashed a new wave of COVID-19 outbreaks. The efficacy of molnupiravir, an approved drug, is still unknown in patients infected with the Omicron variant.Objective: Evaluated the antiviral efficacy and safety of molnupiravir in patients infected with SARS-CoV-2 Omicron variant, with symptom duration within 5 days.Methods: We conducted a randomized, controlled trial involving patients with mild or moderate COVID-19. Patients were randomized to orally receive molnupiravir (800 mg) plus basic treatment or only basic treatment for 5 days (BID). The antiviral efficacy of the drug was evaluated using reverse transcriptase polymerase chain reaction.Results: Results showed that the time of viral RNA clearance (primary endpoint) was significantly decreased in the molnupiravir group (median, 9 days) compared to the control group (median, 10 days) (Log-Rank p = 0.0092). Of patients receiving molnupiravir, 18.42% achieved viral RNA clearance on day 5 of treatment, compared to the control group (0%) (p = 0.0092). On day 7, 40.79%, and 6.45% of patients in the molnupiravir and control groups, respectively, achieved viral RNA clearance (p = 0.0004). In addition, molnupiravir has a good safety profile, and no serious adverse events were reported.Conclusion: Molnupiravir significantly accelerated the SARS-CoV-2 Omicron RNA clearance in patients with COVID-19.Clinical Trial Registration: [chictr.org.cn], identifier [ChiCTR2200056817].

BackgroundAccumulating evidence has shown that diabetes has an impact on bone metabolism with conflicting results. Furthermore, little is known about the relationship of prediabetes with bone mineral density (BMD). Therefore, we explored the association between BMD and glucometabolic status in adults in the US.MethodsIn this cross-sectional study, we extracted and analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. A total of 14610 subjects aged 40 ≥ years diagnosed with diabetes, prediabetes, or normal glucose regulation (NGR) and had available data on BMD were eligible.ResultsThe prevalence of prediabetes and diabetes in US adults aged 40 ≥ years were 39.2% and 26.4%, respectively. After multivariable adjustment, we found an increasing trend of BMD at the total hip, femoral neck, and lumbar spine with glucometabolic conditions from NGR and prediabetes to diabetes in adults aged ≥ 40 years in the US. This trend was more prominent in women than that in men. Fasting plasma glucose (FPG) and HbA1c levels were also positively correlated with BMD.ConclusionsGlucometabolic conditions were significantly associated with BMD values in US adults.