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Abstract Background The progression of tumours is related to abnormal phospholipid metabolism. This study is anticipated to present a fresh perspective for disease therapy targets of hepatocarcinoma caused by hepatitis B virus in the future by screening feature genes related to phospholipid metabolism. Methods This study analysed GSE121248 to pinpoint differentially expressed genes (DEGs). By examining the overlap between the metabolism-related genes and DEGs, the research focused on the genes involved in phospholipid metabolism. To find feature genes, functional enrichment studies were carried out and a network diagram was proposed. These findings were validated via data base of The Cancer Genome Atlas (TCGA). Further analyses included immune infiltration studies and metabolomics. Finally, the relationships between differentially abundant metabolites and feature genes were confirmed by molecular docking, providing a thorough comprehension of the molecular mechanisms. Results The seven genes with the highest degree of connection (PTGS2, IGF1, SPP1, BCHE, NR1I2, NAMPT, and FABP1) were identified as feature genes. In the TCGA database, the seven feature genes also had certain diagnostic efficiency. Immune infiltration analysis revealed that feature genes regulate the infiltration of various immune cells. Metabolomics successfully identified the different metabolites of the phospholipid metabolism pathway between patients and normal individuals. The docking study indicated that different metabolites may play essential roles in causing disease by targeting feature genes. Conclusions In this study, for the first time, it reveals the possible involvement of genes linked to phospholipid metabolism-related genes using bioinformatics analysis. Identifying genes and probable therapeutic targets could provide clues for the further treatment of disease.

ABSTRACTBackground Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials.Research design and methods Study-1 involved subjects were randomized (1:1:1) to receive 20 μg ReCOV, 40 μg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 μg ReCOV (pilot batch, ReCOV HA), 20 μg ReCOV (commercial batch, ReCOV TC), or 30 μg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster.Results Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence.Conclusions Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV’s potential for enhanced protection, supported by strong cross-neutralization and immune persistence.Clinical Trial Registration Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Abstract Background The time‐series data of the Normalized Difference Vegetation Index (NDVI) is a crucial indicator for global and regional vegetation monitoring. However, the current assessment of global and regional long‐term vegetation changes is subject to large uncertainties due to the lack of spatiotemporally continuous time‐series data sets. Methods In this study, a long time‐series monthly NDVI data set with a spatial resolution of 250 m from 1982 to 2020 was developed by combining Moderate Resolution Imaging Spectroradiometer (MODIS) and AVHRR (Advanced Very High‐Resolution Radiometer) time‐series NDVI products using the Random Forest (RF) downscaling model. Results Compared to the MODIS NDVI product, the fused product shows RMSE and mean absolute error ranging from 0 to 0.075 and from 0 to 0.05, respectively, with R2 values mostly above 0.7. Conclusions The long time‐series NDVI products generated in this study are reliable in terms of accuracy and have great potential for long‐term dynamic monitoring of terrestrial ecosystems on the Qinghai–Tibet Plateau.

Abstract Background miR-200a-3p is involved in the progression of malignant behavior in various tumors, and its mechanism of action in endometrial cancer is speculated to be related to epithelial-mesenchymal transition (EMT). Therefore, this study explored the metastatic mechanism of miR-200a-3p and EMT in endometrial cancer, with the aim of identifying potential therapeutic targets. Methods qRT-PCR was used to analyze miR-200a-3p expression in HEC-1B and Ishikawa cell lines. The cell proliferation assay, transwell assay, and cell scratch test were used to assess changes in the malignant phenotypes of cells after regulating miR-200a-3p expression. Changes in EMT-related protein zinc finger E-box binding homeobox 1 (ZEB1) were detected after regulating miR-200a-3p expression. An endometrial carcinoma transplantation mouse tumor model was constructed, and multiple EMT-related proteins were examined. Results The expression of miR-200a-3p and ZEB1 in the endometrial cancer cell lines was higher than in normal endometrial epithelial cell lines (P

Abstract Background Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. Case presentation A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. Conclusion The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.

Abstract MiRNAs in mesenchymal stem cells (MSCs)-derived exosome (MSCs-exo) play an important role in the treatment of sepsis. We explored the mechanism through which MSCs-exo influences cognitive impairment in sepsis-associated encephalopathy (SAE). Here, we show that miR-140-3p targeted Hmgb1. MSCs-exo plus miR-140-3p mimic (Exo) and antibiotic imipenem/cilastatin (ABX) improve survival, weight, and cognitive impairment in cecal ligation and puncture (CLP) mice. Exo and ABX inhibit high mobility group box 1 (HMGB1), IBA-1, interleukin (IL)-1β, IL-6, iNOS, TNF-α, p65/p-p65, NLRP3, Caspase 1, and GSDMD-N levels. In addition, Exo upregulates S-lactoylglutathione levels in the hippocampus of CLP mice. Our data further demonstrates that Exo and S-lactoylglutathione increase GSH levels in LPS-induced HMC3 cells and decrease LD and GLO2 levels, inhibiting inflammatory responses and pyroptosis. These findings suggest that MSCs-exo-mediated delivery of miR-140-3p ameliorates cognitive impairment in mice with SAE by HMGB1 and S-lactoylglutathione metabolism, providing potential therapeutic targets for the clinical treatment of SAE.

Abstract Background Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC. However, the expression and biological function of OTUD5 in HCC are still controversial. Results We determined that the expression of OTUD5 was significantly upregulated in HCC tissues. High levels of OTUD5 were also detected in most HCC cell lines. TCGA data analysis demonstrated that high OTUD5 expression indicated poorer overall survival in HCC patients. OTUD5 silencing prominently suppressed HCC cell proliferation, while its overexpression markedly enhanced the proliferation of HCC cells. Mass spectrometry analysis revealed solute carrier family 38 member 1 (SLC38A1) as a candidate downstream target protein of OTUD5. Coimmunoprecipitation analysis confirmed the interaction between OTUD5 and SLC38A1. OTUD5 knockdown reduced and OTUD5 overexpression increased SLC38A1 protein levels in HCC cells. However, OTUD5 alteration had no effect on SLC38A1 mRNA expression. OTUD5 maintained SLC38A1 stability by preventing its ubiquitin-mediated proteasomal degradation. SLC38A1 silencing prominently attenuated the OTUD5-induced increase in HCC cell proliferation. Finally, OTUD5 knockdown markedly suppressed the growth of HCC cells in vivo. Conclusions OTUD5 is an oncogene in HCC. OTUD5 contributes to HCC cell proliferation by deubiquitinating and stabilizing SLC38A1. These results may provide a theoretical basis for the development of new anti-HCC drugs.

In this study, a strain with good antibacterial effect was screened and identified from traditional soybean paste in Northeast China. The strain was identified using methods such as 16S rDNA and housekeeping gene gyrA sequencing analysis. Its bacteriocins were crude extracted using ethyl acetate extraction, further purified using dextran gel Sephadex-G50 and high performance liquid chromatography (HPLC) techniques, combined with SDS-PAGE and liquid chromatography-mass spectrometry (LC-MS/MS) for identification. The antibacterial effect of the bacteriocin on Staphylococcus aureus was analyzed by determining the minimum concentration and growth inhibition curve. Additionally, the stability of the bacteriocins was investigated by exploring its thermal stability, pH tolerance, and resistance to proteases. Results showed that the Bacillus subtilis S1-2 strain had the best antibacterial effect on Staphylococcus aureus and Listeria monocytogenes. The bacteriocin produced by the strain was identified as subtilosin A, with molecular weight of approximately 3 kDa, and demonstrated a significant inhibitory effect on Staphylococcus aureus and Listeria monocytogenes. The minimum inhibitory concentration against Staphylococcus aureus was 0.625 mg/mL. Furthermore, the bacteriocin exhibited stable antibacterial activity between 20~80 ℃ and even between 100~120 ℃. It showed the highest antibacterial activity in the pH range of 6.0~8.0, as well as good acid and alkali tolerance with pH values of 1 and 10. Furthermore, it could be hydrolyzed by proteinase K, pepsin, and trypsin. In conclusion, Bacillus subtilis S1-2 and its bacteriocin subtilosin A have great potential in food preservation due to their strong antibacterial activities.

Abstract Background Endometriosis frequently results in pain and infertility. While conservative surgery offers some relief, it often falls short of ensuring satisfactory pregnancy outcomes. Adjuvant GnRH-a is administered post-surgery to mitigate recurrence; however, its impact on pregnancy outcomes remains debated. This study endeavors to assess the efficacy of adjuvant GnRH-a in enhancing pregnancy outcomes post-conservative surgery in endometriosis patients. Methods Databases including PubMed, Embase, the Cochrane Library, Medline (Ovid), Web of Science, and Scopus were rigorously searched up to 02 August 2023, without linguistic constraints. Identified articles were screened using strict inclusion and exclusion criteria. Evaluated outcomes encompassed pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, multiple pregnancy rate, mean postoperative pregnancy interval, recurrence rate, and adverse reaction rate. The Cochrane risk of bias tool and the Jadad score evaluated the included studies’ quality. Subgroup and sensitivity analysis were implemented to analyze the pooled results. A meta-analysis model expressed results as standardized mean difference (SMD) and Risk ratio (RR). Results A total of 17 studies about 2485 patients were assimilated. Meta-analysis revealed that post-surgery, the GnRH-a cohort experienced a marginally elevated pregnancy rate (RR = 1.20, 95% CI = 1.02–1.41; P = 0.03) and a reduced mean time to conceive (RR = -1.17, 95% CI = -1.70- -0.64; P

Apoptosis signal-regulated kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase (MAP3K) family, whose activation and regulation are intricately associated with apoptosis. ASK1 is activated in response to oxidative stress, among other stimuli, subsequently triggering downstream JNK, p38 MAPK, and mitochondria-dependent apoptotic signaling, which participate in the initiation of tumor cell apoptosis induced by various stimuli. Research has shown that ASK1 plays a crucial role in the apoptosis of lung cancer, breast cancer, and liver cancer cells. Currently, the investigation of effective ASK1 activators is a hot topic in research on tumor cell apoptosis. Synthetic compounds such as human β-defensin, triazolothiazide derivatives and heat shock protein 27 inhibitors; natural compounds such as quercetin, Laminarina japonica polysaccharide-1 peptide and theabrownin; and nanomedicines such as cerium oxide nanoparticles, magnetite FeO nanoparticles and silver nanoparticles can activate ASK1 and induce apoptosis in various tumor cells. This review extensively investigates the roles and activation mechanisms of ASK1, explores its impact on a variety of apoptotic signaling pathways, and discusses the potential therapeutic applications of various ASK1 activators in cancer treatment. In addition, this paper provides an in-depth discussion of the future development of this field and proposes a promising method for further research and clinical progress.

ABSTRACT: In the late growth stage of commercial Pekin ducks, a significant increase in feed intake and a decline in body weight gain have been observed, leading to impaired feed conversion efficiency. To address this issue, we investigated alterations in production performance, blood biochemical indices, ileum tissue architecture, and microbial community structure in Pekin ducks. The primary objective was to provide robust data supporting the improvement of meat duck production efficiency during the late growth stage (28–42-days-old). Forty 28-day-old Pekin ducks were randomly assigned to 8 replicates, with five ducks per replicate. The rearing period lasted 14 days, with feed and water provided ad libitum. Our findings indicated a significant increase in Pekin duck body and heart weights with advancing age (P < 0.05). Moreover, serum antioxidant enzyme and high-density lipoprotein concentrations significantly increased, whereas triglyceride levels decreased (P < 0.05). Notably, the height of the ileal villi was significantly reduced (P < 0.05). The microbial community structure of the ileum exhibited significant changes as ducks aged, accompanied by a substantial increase in microbial flora diversity, particularly with the formation of more tightly connected microbial network modules. Time-dependent enrichment was observed in microbial gene functions related to energy metabolism pathways. At the genus level, Sphingomonas and Subdoligranulum have emerged as crucial players in microbial differential functional pathways and network formation. These bacteria likely serve as the key driving factors in the dynamic microbial changes that occur in Pekin ducks over time. Overall, our findings suggest a potential decline in the absorption function of the small intestine and fat deposition performance of Pekin ducks during later growth stages, which may be attributed to the maturation and proliferation of the gut microbial community.

This study aims to utilize the Small Baseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) technique and Google Earth optical remote sensing images to analyze the area within 20 ​km around the epicenter of a M 3.9, earthquake that occurred in Tanchang County, Gansu Province, on December 28, 2020. The objective is to identify potential earthquake-induced landslides, assess their scale, and determine their impact range. The study results reveal the successful identification of two potential landslides in the 20 ​km radius around the epicenter. Through time-series deformation analysis, it was observed that these potential landslides were significantly influenced by both the earthquake and rainfall. Further estimation of these potential landslides indicates maximum depths of 7.4 ​m and 14.1 ​m for the failure surfaces, with volumes of 9.02 ​× ​104 ​m3 and 25.5 ​× ​104 ​m3, respectively. Finally, based on the simulation analysis of Massflow software, the maximum thickness of soil accumulation in the final accumulation area after sliding of the potential landslide in Shangyaai is 12 ​m, the area of the final accumulation area is 1.75 ​× ​104 ​m2, and the farthest movement distance is 1124 ​m. The maximum thickness of soil accumulation in the final accumulation area after sliding of the potential landslide in Wangshancun is 8 ​m, the area of the final accumulation area is 7.89 ​× ​104 ​m2, and the farthest movement distance is 742 ​m.

With the change of seasons, the shear strength of saline soil subgrade filler will change with the change of external temperature, which will aggravate the adverse effects of seismic on the subgrade. To explore the influence of seismic action on the stability of saline soil subgrade under the influence of temperature on the strength of saline soil subgrade filler, this paper first carried out saline soil shear tests at different temperatures to obtain the influence of temperature on the shear strength of saline soil. Then, the temperature field of the saline soil subgrade was simulated, and then based on the subgrade isothermal stratification model and FLAC3D, the displacement and acceleration amplification effects of seismic action on the shady slope, sunny slope and subgrade of saline soil subgrade in different months were analyzed. The following conclusions were finally drawn: under the action of seismic, In the process of the change of subgrade temperature of Qarhan - Golmud Expressway between −7.7 ​°C and 27 ​°C, the change of saline soil cohesion is the main factor affecting the stability of subgrade slope, and the maximum and minimum values of subgrade surface settlement appear in September and June of each year, respectively. In August, the differences of settlement between the shady slope and the sunny slope shoulder of the subgrade were the largest, and the acceleration of the shady slope and the sunny slope and the inside of the subgrade changed most significantly in the vertical direction. Special attention should be paid to the seismic early warning in the above key months; In the range from both sides of the shoulder to the centerline of the roadbed, the acceleration amplification effect starts to increase significantly from about 3m from the centerline of the roadbed to the centerline, so it is necessary to pay attention to the seismic design of this range.

Background To study the age‐adjusted Charlson comorbidity index (ACCI) scale, which is a comprehensive quantification of multimorbidity coexistence, for the assessment of the risk of acute myocardial infarction death in elderly people. Methods and Results A total of 502 older patients with acute myocardial infarction were studied at Qilu Hospital from September 2017 to March 2022. They were categorized on the basis of ACCI into low (≤5), intermediate (6, 7), and high (≥8) risk groups. Hospitalization duration was observed, with death as the end point. least absolute shrinkage and selection operator regression was used to screen variables, 10‐fold cross‐validation was performed to validate the screened variables, a Cox regression nomogram predicting the risk of patient death was prepared, hazard ratio with 95% CI was calculated, a nomogram calibration curve was constructed, and a receiver operating characteristic curve, decision curve analysis, and a clinical impact curve were established. From 62 potential factors in a least absolute shrinkage and selection operator regression, 12 were selected via 10‐fold cross‐validation. Retain variables with significant statistical differences in the Cox regression. A nomogram of the risk of death from acute infarction was constructed, and risk factors included ventricular tachycardia/fibrillation, atrial fibrillation, nicorandil, angiotensin‐converting enzyme inhibitors/angiotensin‐converting enzyme inhibitors, β blockers, and ACCI score, carbon dioxide combining power, and blood calcium concentration. Conclusions The ACCI score effectively assesses multimorbidity in the older patients. As ACCI rises, the death risk from acute myocardial infarction grows. The study's nomogram is valid and clinically applicable.

This study aims to construct a predictive model for assessing the risk of cognitive decline among elderly patients diagnosed with type 2 diabetes and validate its effectiveness. A total of 480 elderly patients with type 2 diabetes who signed a family doctor and underwent chronic disease management were selected and divided into a cognitive decline group (n = 62) and a non-cognitive decline group (n = 418) based on cognitive decline. Various clinical variables, lifestyle choices, medication regimens, complications, and medical histories were subjected to statistical analysis for both groups. Univariate and multivariate logistic regression analyses were performed to identify risk factors, based on which a risk prediction model was constructed. Hosmer and Lemeshow were used to investigate the goodness of fit of the risk prediction model, and Statistical Product and Service Solutions (SPSS) was used to draw Receiver Operating Characteristic (ROC) curves to assess the predictive value of the risk prediction model. Age, infrequent exercise, inadequate sleep, and the presence of depression emerged as significant risk factors for cognitive decline. The goodness-of-fit test using the Hosmer and Lemeshow statistic yielded χ2 = 0.041 and p = 0.855, confirming the model’s appropriateness. ROC curve analysis demonstrated an Area Under the Curve (AUC) of 0.912 (95% CI: 0.874 to 0.950), underscoring the model’s predictive capability. Age, infrequent exercise, inadequate sleep and depression could be risk factors for cognitive decline in elderly individuals with type 2 diabetes, and the proposed risk prediction model displays robust predictive accuracy for identifying those at risk of cognitive decline.

Abstract Background Circulating tumor cells (CTCs) play a crucial role in the early diagnosis and prognosis of lung cancer. Identification of a more suitable sample source could be a breakthrough towards enhancing CTC detectability in early‐stage lung cancer. We investigated the differences in detectable CTCs between peripheral arterial and venous blood in early‐ and mid‐stage lung cancer patients undergoing surgery and analyzed the association between clinicopathological factors and detectable CTCs in peripheral arterial and venous blood. Methods Peripheral arterial and venous blood was collected in 5‐mL samples from 56 patients with surgically resected and pathologically clear at early‐ or mid‐stage lung cancer. Blood specimens were enriched for CTCs based on isolation by size of epithelial tumor cells. The CTCs were identified using Swiss Giemsa staining and immunohistochemistry for CD45/CD31. Results In stage I lung cancer, CTC‐positive rate was significantly higher in peripheral arterial than in venous blood (45.45% vs. 17.39%). There was no significant difference in the number of detectable CTCs between peripheral arterial and venous blood. A low degree of differentiation was associated with a high positive rate of CTCs in peripheral venous blood. The number of circulating tumor microemboli was significantly higher in patients with tumor size >3 cm compared with ≤3 cm. Conclusion CTC levels in peripheral arterial and venous blood differed little in lung cancer patients.Compared to peripheral venous blood, peripheral arterial blood had a higher CTC positivity rate in early‐stage lung cancer.This study was favorable for early detection and monitoring of lung cancer.

Abstract Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics.

Abstract The Fscn2 (Fascin2) gene encodes an actin cross-linking protein that is involved in the formation of hair cell stereocilia and retina structure. Mutations in Fscn2 gene have been linked to hearing impairment and retinal degeneration in humans and mice. To understand the function of the Fscn2 gene, we generated the Fscn2 knockout mice, which showed progressive loss of hearing and hair cells. Our goal of the present study was to investigate the mechanism underlying cochlear cell death in the Fscn2 knockout mice. Microarray analysis revealed upregulation of expression of PARVB, a local adhesion protein, in the inner ears of Fscn2 knockout mice at 8 weeks of age. Further studies showed increased levels of PARVB together with cleaved-Caspase9 and decreased levels of ILK, p-ILK, p-AKT, and Bcl-2 in the inner ears of Fscn2 knockout mice of the same age. Knockdown of Fscn2 in HEI-OCI cells led to decreased cell proliferation ability and migration rate, along with increased levels of PARVB and decreased levels of ILK, p-ILK, p-AKT, Bcl-2 and activated Rac1 and Cdc42. Overexpression of Fscn2 or inhibition of Parvb expression in HEI-OC1 cells promoted cell proliferation and migration, with increased levels of ILK, p-ILK, p-AKT, and Bcl-2. Finally, FSCN2 binds with PPAR-γ to reduce its nuclear translocation in HEI-OC1 cells, and inhibition of PPAR-γ by GW9662 decreased the level of PARVB and increased the levels of p-AKT, p-ILK, and Bcl-2. Our results suggest that FSCN2 negatively regulates PARVB expression by inhibiting the entry of PPAR-γ into the cell nucleus, resulting in inhibition of ILK-AKT related pathways and of cochlear cell survival in Fscn2 knockout mice. Our findings provide new insights and ideas for the prevention and treatment of genetic hearing loss.

Abstract Objective This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation. Methods From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation, diagnosed with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed. Results A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder. Conclusion Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase.

It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer’s disease. The large-scale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.

In the realm of cross-modal retrieval research, hash methods have garnered significant attention from scholars due to their high retrieval efficiency and low storage costs. However, these methods often sacrifice a considerable amount of semantic features when mapping multi-modal characteristics to a low-dimensional space. Moreover, the focus of hash learning has primarily been on inter-modal similarity learning, neglecting the importance of intra-modal similarity learning. To address these issues, this paper proposes a novel cross-modal hash method called Deep Hashing Similarity Learning for Cross-modal Retrieval (DHSL). DHSL incorporates relation networks into the hash method, enabling pairwise matching between images and texts. This approach effectively bridges the heterogeneity gap between images and texts while simultaneously emphasizing the intra-modal similarity information within both modalities. The result is a hash similarity matrix that captures both inter-modal similarity and intra-modal discriminability. Considering that the process of transforming high-dimensional features into hash codes often leads to a loss of important semantic information, we introduce a feature selector to enhance the features. This selector filters out distinctive features from the original feature set and combines them with low-dimensional features to complement the semantic information. Moreover, we introduce weighted cosine triplet loss and quantization loss to constrain the hash representation in the Hamming space, thereby learning high-quality hash codes. Comprehensive experimental results on two benchmark datasets, NUS-WIDE and MIRFlickr25K, demonstrate that DHSL outperforms the state-of-the-art cross-modal hash methods.

Abstract Background Increasing number of studies have demonstrated certain patterns of microbial changes in gynecological diseases; however, the interaction between them remains unclear. To evaluate the consistency or specificity across multiple studies on different gynecological diseases and microbial alterations at different sites of the body (gut and genital tract), we conducted a systematic review and meta-analysis. Methods We searched PubMed, Embase, Web of Science, and Cochrane Library up to December 5, 2022(PROSPERO: CRD42023400205). Eligible studies focused on gynecological diseases in adult women, applied next-generation sequencing on microbiome, and reported outcomes including alpha or beta diversity or relative abundance. The random-effects model on standardized mean difference (SMD) was conducted using the inverse-variance method for alpha diversity indices. Results Of 3327 unique articles, 87 eligible studies were included. Significant decreases were found in gut microbiome of patients versus controls (observed species SMD=-0.35; 95%CI, -0.62 to -0.09; Shannon index SMD=-0.23; 95%CI, -0.40 to -0.06), whereas significant increases were observed in vaginal microbiome (Chao1 SMD = 1.15; 95%CI, 0.74 to 1.56; Shannon index SMD = 0.51; 95%CI, 0.16 to 0.86). Most studies of different diagnostic categories showed no significant differences in beta diversity. Disease specificity was observed, but almost all the changes were only replicated in three studies, except for the increased Aerococcus in bacterial vaginosis (BV). Patients with major gynecological diseases shared the enrichment of Prevotella and depletion of Lactobacillus, and an overlap in microbes was implied between BV, cervical intraepithelial neoplasia, and cervical cancer. Conclusions These findings demonstrated an association between alterations in gut and genital microbiota and gynecological diseases. The most observed results were shared alterations across diseases rather than disease-specific alterations. Therefore, further investigation is required to identify specific biomarkers for diagnosis and treatment in the future.

ABSTRACT: Milk fat globule epidermal growth factor 8 (MFG-E8) and whey protein have emerged as promising bionutrient supplements for enhancing skeletal muscle mass and function. In the present study, aging-related sarcopenia rat model was employed to elucidate the effects of the combined administration of MFG-E8 and whey protein on the catabolism and anabolism of gastrocnemius protein. Combined intervention led to notable enhancements in the antioxidative stress status and mitochondrial biogenesis capacity of gastrocnemius muscle fibers in the aging rats, concomitant with a significant inhibition of lipid accumulation. Moreover, the synergistic effect of MFG-E8 and whey protein was found to exert modulatory effects on key signaling pathways, including PI3K/Akt/PGC-1α pathway and MAPK/ERK signaling pathways in the gastrocnemius muscle of the aging rats. Specifically, this combined intervention was observed to promote mitochondrial biogenesis and regulate the expression of protein anabolism and catabolism-related regulators, thereby facilitating the alleviation of mitochondrial oxidative stress and enhancing biogenesis in gastrocnemius tissues. The findings of our study provide compelling evidence for the potential of MFG-E8 as a promising dietary supplement with antisarcopenic properties to ameliorate muscle protein metabolism disorders and mitigate mitochondrial-mediated myoblast apoptosis induced by oxidative stress.

This study presents a snow drought assessment method using snow water equivalent products to examine the patterns and differences in snow drought events in China from 1980 to 2020. The findings indicate that snow drought changes over the past 40 years can be categorized into three stages: The most severe snow drought occurred in the 1980s, followed by alleviation until 2009, and a subsequent aggravation after 2010. Light snow drought has the widest distribution and shows an increasing trend, whereas medium, heavy, and extreme snow droughts decrease gradually but show a decrease followed by an increasing trend over time. The distribution of snow drought in China displays significant spatial heterogeneity, with areas such as Alxa League in Inner Mongolia, Hami, Turpan, Bayingol, Xinjiang, and the Tibetan Plateau hinterland experiencing frequent snow drought events. Moreover, the low-altitude region has the largest average annual proportion of extreme drought, whereas the high-altitude region has the highest proportion of heavy drought. Among the three snow-dominant areas, Northern Xinjiang has the largest proportion of snow drought areas. The Northeast-Inner Mongolia has the highest proportion of extreme drought while the Tibetan Plateau exhibited abrupt changes in snow drought occurrence. These results contribute to a better understanding of the underlying mechanisms of snow drought changes, as well as serve as a foundation for the protection of the ecological environment.

Ophthalmic and many systemic diseases may damage the eyes, resulting in changes in the composition and content of biomolecules in ocular biofluids such as aqueous humor and tear. Therefore, the biomolecules in biofluids are potential biomarkers to reveal pathological processes and diagnose diseases. Raman spectroscopy is a non-invasive, label-free, and cost-effective technique to provide chemical bond information of biomolecules and shows great potential in the detection of ocular biofluids. This review demonstrates the applications of Raman spectroscopy technology in detecting biochemical components in aqueous humor and tear, then summarizes the current problems encountered for clinical applications of Raman spectroscopy and looks forward to possible approaches to overcome technical bottlenecks. This work may provide a reference for wider applications of Raman spectroscopy in biofluid detection and inspire new ideas for the diagnosis of diseases using ocular biofluids.

Hansen, D. T. (2021). Reimagining the call to teach: A witness to teachers and teaching. Teachers College Press. David Hansen’s book Reimaging the Call to Teach: A Witness to Teachers and Teaching, in very nuanced, subtle, and complicated ways, inquires into teaching as a calling: it enacts and embodies the educational moments and space in teaching filled with uncertainties and complexities as “being with” (p. 33) others, “linking the past, present and future” (p. xiii). Hansen, as it rarely happens, bears an attuned and amplifying witness in sitting in on the classrooms as well as ongoing conversions to 16 public teachers over 2 years who participated in the “Person Project” (p. 52), which assembles teachers’ testimonials about teaching and what it means to “be a person in the world today” (p. 54) without imposing objectifying measurements and standards. In the book, the messy and rough ground of teaching, full of feelings, hesitations, and confusions, is not analyzed and decoded but rather felt, embodied, and described more comprehensively. As Hansen suggests, “I believe what is put forward here is a better description of the unity of the aesthetic, ethical, moral, and intellectual aspects of teaching—of the gestalt of teaching—of the meaning of teaching” (p. 57).

Coronavirus disease 2019 (COVID-19) is continuously posing high global public health concerns due to its high morbidity and mortality. This study aimed to construct a convenient risk model for predicting in-hospital mortality of COVID-19 Omicron variant. A total of 1324 hospitalized patients with Omicron variant were enrolled from Beijing Anzhen Hospital. During hospitalization, the Omicron variant mortality rate was found to be 24.4%. Using the datasets of clinical demographics and laboratory tests, three machine learning algorithms, including best subset selection, stepwise selection, and least absolute shrinkage and selection operator regression analyses were employed to identify the potential predictors of in-hospital mortality. The results found that a panel of twenty-four clinical variables (including age, hyperlipemia, stroke, tumor, and several cardiovascular markers) identified by stepwise selection model exhibited significant performances in predicting the in-hospital mortality of COVID-19. The resultant nomogram showed good discrimination, highlighted by the areas under the curve values of 0.88 for 10 days, 0.81 for 20 days, and 0.82 for 30 days, respectively. Furthermore, decision curve analysis showed a significant reliability and precision for the established stepwise selection model. Collectively, this study developed an accurate and convenience risk model for predicting the in-hospital mortality of COVID-19 Omicron.

Abstract Introduction ReCOV is a recombinant protein vaccine that aims to induce cross-neutralization against SARS-CoV-2 variants. The phase I and phase II studies were conducted in New Zealand and the Philippines, respectively, for ReCOV primary series. Methods Both studies were randomized, double-blind, placebo-controlled designed among COVID-19 vaccine-naïve healthy adults who received two doses of study vaccination with a 21-day interval. In phase I, 100 younger (15–55 years) and older (56–80 years) subjects were 4:1 randomized to receive ReCOV (20 µg or 40 µg) or placebo. In the phase II study, 347 subjects (≥ 18 years) were 2:1 randomized to receive 40 µg ReCOV or placebo. Subjects that received ReCOV were followed up for 6 months after the second dosing. The safety outcomes included solicited and unsolicited AEs, SAEs, and AESIs. The immunogenicity outcomes were live-virus neutralizing antibody (NAb) against prototype, while pseudovirus NAbs against several SARS-CoV-2 variants were included in phase II as well. Results No related SAE, AESI, or AE leading to early discontinuation were reported. The AE incidences were higher in ReCOV groups than placebo group in phase I while they were similar between study groups in phase II. The majority of solicited AEs were mild or moderate with median duration of 1.0–4.0 days. The common (≥ 10%) solicited AEs in phase I were injection site reactions, headache, pyrexia, fatigue, and myalgia, and common reported (≥ 5%) ones in phase II included injection site pain, headache, and pyrexia. Robust neutralizing activities against the prototype were observed in ReCOV groups, peaking at 14 days post the second dosing: in phase I, the GMTs for 20 μg and 40 μg ReCOV groups were 1643.2 IU/mL (95% CI 1188.5, 2271.9) and 1289.2 IU/mL (95% CI 868.3, 1914.1) in younger adults, and 1122.3 IU/mL (95% CI 722.6, 1743.1) and 680.3 IU/mL (95% CI 440.2, 1051.4) in older adults, respectively, while in the ReCOV group of phase II, the GMTs for subjects with seronegative and seropositive status at baseline were 3741.0 IU/mL (95% CI 3113.4, 4495.0) and 6138.3 IU/mL (95% CI 5255.1, 7169.9), respectively. In phase II, substantial levels of pseudovirus NAbs against SARS-CoV-2 variants were demonstrated; the peak GMTs for prototype, Omicron BA.2, and BA.4/5 were 8857, 4441, and 2644, and 15,667.3, 7334.3, and 4478.8 among seronegative and seropositive subjects, respectively. The neutralization persisted till 6 months post the second dosing, with only 2.5- to 5.2-fold declines for Omicron variants. Conclusions Two doses of 20 µg and 40 µg ReCOV are safe and immunogenic against SARS-CoV-2 prototype. The cross-neutralizing activities against Omicron variants support ReCOV advance to late-stage clinical trials. Trial Registration Phase I study, clinicaltrials.gov NCT04818801; phase II study, clinicaltrials.gov NCT05084989.

Abstract Background Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown. Methods The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore’s study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed. Results A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4 + Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy. Conclusion A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC.

Abstract The possibilities of cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans and important livestock species are not yet known. Herein, we used the structural and genetic alignment and surface potential analysis of the amino acid (aa) in angiotensin-converting enzyme 2 (ACE2), tyrosine kinase receptor UFO (AXL), and neuropilin 1 (NRP1) in different species with substantial public health importance. The residues interfacing with the N-terminal domain (NTD) or receptor-binding domain (RBD) of S were aligned to screen the critical aa sites that determined the susceptibility of the SARS-CoV-2 to the host. We found that AXL and NRP1 proteins might be used as the receptors of SARS-CoV-2 in bovines. However, ACE2 protein may not be considered to be involved in the cross-species transmission of SARS-CoV-2 VOCs in cattle because the key residues of the ACE2-S-binding interface were different from those in known susceptible species. This study indicated that emerging SARS-CoV-2 variants potentially expand species tropism to bovines through AXL and NRP1 proteins.

ABSTRACT: Pro-Glu-Trp (PEW) and Leu-Leu-Trp (LLW) are peptides derived from whey protein digestive products; both peptides exhibit xanthine oxidase inhibitory activity in vitro. However, it remains unclear whether these peptides can alleviate hyperuricemia (HUA) in vivo. In this study, we investigated the roles of PEW and LLW, both individually and in combination, in alleviating HUA induced by potassium oxonate and hypoxanthine. Together, PEW and LLW exhibited synergistic effects in reducing the serum levels of uric acid (UA), creatinine, and blood urea nitrogen, as well as increasing the fractional excretion of UA. The combined treatment with PEW and LLW inhibited UA synthesis, promoted UA excretion, and restored renal oxidative stress and mitochondrial damage. Moreover, the combined treatment alleviated dysbiosis of the gut microbiota, characterized by increased helpful microbial abundance, decreased harmful bacterial abundance, and increased production of short-chain fatty acids. Taken together, these results indicate that the combination of PEW and LLW mitigate HUA and kidney injury by rebalancing UA synthesis and excretion, modulating gut microbiota composition, and improving oxidative stress.

Infection with the Hantaan virus (HTNV) may result in severe hemorrhagic fever with renal syndrome (HFRS). The functions of HLA-E-restricted CD8+ T lymphocytes in virus control and vaccine development have recently received increased attention. The purpose of this research is to discover HLA-E-restricted CD8+ T cell epitopes on HTNV as well as the features of these epitope-specific CD8+ T cells in HFRS patients. To anticipate HLA-E-restricted HTNV epitopes, the NetMHCpan servers were utilized. The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E. The number and features of HLA-E-restricted epitope-specific CD8+ T lymphocytes in HFRS patients were investigated using tetramer staining, intracellular cytokine labeling, proliferation, and cytotoxicity assays. Six HTNV-derived HLA-E-restricted CD8+ T cell epitopes were found in this study. In mild/moderate HFRS patients, the frequency of HLA-E-restricted epitope-specific CD8+ T cells was greater than in severe/critical patients. CD38+HLA-DR+ HLA-E-restricted CD8+ T cells were identified. Meanwhile, CD45RA+CCR7− effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated. Notably, CD8+ T cells from milder HFRS patients produced more interferon-γ, interleukin-2, and granzyme B, had a stronger proliferative potential, and were inversely linked with the amount of plasma HTNV virus load. Furthermore, HLA-E-restricted epitope-specific CD8+ T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS. Taken together, the findings demonstrate the protective effects of HLA-E-restricted CD8+ T cells during HTNV infection, suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.

Abstract Background There is few evidence of right ventricular (RV) function in fetuses with gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the RV function of fetuses using routine and two-dimensional speckle-tracking echocardiography (2D STE) to determine the effects of well-controlled GDM in the third trimester. Methods We used a Philips Epiq7C ultrasound instrument to obtain RV data sets from 63 subjects from July 2019 to February 2022. We compared the free wall thickness (FWT), fractional area change (FAC), Tei index (TEI), tricuspid annular plane systolic excursion (TAPSE) and free wall longitudinal strain(FWLS)of the RV in mothers with well-controlled GDM and normal gestational age-matched fetuses. Results 63 third trimester fetuses (32 GDM; 31 healthy controls) met the enrolment criteria. Significant differences in fetal RV were detected between the GDM and control groups for the FAC (36.35 ± 6.19 vs. 41.59 ± 9.11; P = 0.008) and the FWLS (-18.28 ± 4.23 vs. -20.98 ± 5.49; P = 0.021). There was a significant difference among the segmental strains of the base, middle and apex of the RV free wall in the healthy controls (P = 0.003), but in the GDM group, there was no statistical difference (p = 0.076). RV FWLS had a strong correlation with FAC (r = 0.467; P = 0.0002). Conclusions In well-controlled GDM, there was measurable fetal RV hypertrophy and significant systolic function decline, indicating the presence of ventricular remodeling and dysfunction. 2D-STE can evaluate the RV free wall contraction in a more comprehensive way.

Abstract Due to anthropogenic activities, heavy metal (HM) pollution in soils has increased, resulting in severe ecological problems and posing a constant threat to human health. Among various remediation methods, bacterial remediation is a relatively clean, efficient, and minimally negative approach. However, bacterial agents face multiple environmental stresses, making them challenging to achieve long-lasting and stable restoration effects. To address this issue, supportive organic substances such as biochar can be added to the soil with bacteria. According to bibliometric studies, integrating biochar and bacteria is extensively researched and widely used for HM-contaminated soil remediation. By integrating biochar and bacteria, heavy metals in the soil can be remediated, and soil conditions can be improved over time. Bacteria can also better promote plant growth or contribute effectively to phytoremediation processes when assisted by biochar. However, the remediation agents integrating biochar and bacteria are still some distance away from large-scale use because of their high cost and possible environmental problems. Therefore, further discussion on the interaction between biochar and bacteria and the integration approach, along with their remediation efficiency and environmental friendliness, is needed to achieve sustainable remediation of HM-contaminated soils by integrating biochar and bacteria. This paper discusses the potential mechanisms of biochar-bacteria-metal interactions, current advancements in biochar-bacteria combinations for HM-contaminated soil treatment, and their application in sustainable remediation, analyzes the interaction between biochar and bacteria and compares the remediation effect of different ways and feedstocks to integrate biochar and bacteria. Finally, future directions of biochar-bacteria combinations are presented, along with evidence and strategies for improving their commercialization and implementation. Graphical Abstract

Super-resolution structured illumination microscopy (SR-SIM) is one of the important techniques that are most suitable for live-cell imaging. The reconstructed SR-SIM images are noisy once the raw images are recorded with low-light exposure. Here, we propose a new network (entitled the ND-SIM network) to denoise the SR images reconstructed using frequency-domain algorithms (FDAs). We demonstrate that ND-SIM can yield artifact-free SR images using raw images with an average photon count down to 20 per pixel while achieving comparable resolution to the ground truth (GT) obtained with high-light exposure. We can envisage that the ND-SIM will be widely applied for the long-term, super-resolution live-cell imaging of various bioprocesses in the future.

AlGaN/GaN high-electron-mobility transistors (HEMTs) are widely used in high-frequency and high-power applications owing to the high two-dimensional electron gas (2DEG) concentration. However, the microscopic origin of the 2DEG remains unclear. This hinders the development of device fabrication technologies, such as threshold voltage modulation, current collapse suppression, and 2DEG concentration enhancement technologies, as well as AlGaN/GaN sensors with very high sensitivity to polar liquids. To clarify the 2DEG microscopic origin, we studied the effects of gas molecules on AlGaN/GaN surfaces through various experiments and first-principles calculations. The results indicated that the adsorption of gas molecules on the AlGaN/GaN surface is an important phenomenon, clarifying the microscopic origin of the 2DEG. This study elucidates the properties of AlGaN/GaN heterojunctions and promotes the development of new fabrication technologies for AlGaN/GaN devices.

Substituting traditional protein feed with palm kernel meal (PKM) in the diet of Tibetan sheep can be a cost-effective feeding strategy. To determine the impact of PKM on flavor development in different adipose tissues of Tibetan sheep, subjects were fed with 15% and 18% of PKM, while the control group received no PKM. The fatty acids and volatile compounds in the samples were then analyzed by GC-MS and HS-GC-IMS. Adding PKM to the diet significantly increased the C12:0, C14:0, C16:0 and C18:1N9 content in adipose tissues compared with the control, and most of these were associated with flavor formation (p < 0.05). The flavor compounds in the adipose tissues predominantly consisted of alcohols, ketones, acids and aldehydes. In particular, including PKM in the diet increased the proportion of ketones but decreased the proportion of alcohols, acids and aldehydes in subcutaneous and tail fat. Specifically, the proportion of acetone, acetoin monomer, 2,3-butanedione, 2-butanone monomer, 2-methyl-2-propanol, 2-methyl-2-propanol and methyl acetate increased significantly in the subcutaneous and tail fat (p < 0.05), while that of ethanol, 1-propanol monomer, butanol monomer, acetic acid monomer and acetic acid monomer decreased. Intermuscular fat exhibited variable results, mainly because the addition of PKM resulted in higher proportions of alcohols, including ethanol, 1-propanol and butanol monomer, especially at 15% PKM. In summary, the addition of PKM improved the flavor of Tibetan sheep fat and increased the amount of favorable volatile flavor compounds. This study can serve as reference for understanding the effects of dietary PKM on the adipose tissue flavor profile of Tibetan sheep.

Background: Scutellaria baicalensis, the dry root of scutellaria baicalensis georgi, is a traditional Chinese medicine with long. In clinic, scutellaria baicalensis is commonly used in prescription for the treatment of depression. Additionally, numerous pre-clinical studies have shown that Scutellaria baicalensis and its active constituents are effective for depression. In this study, we aims to systematically review the roles of scutellaria baicalensis in depression and summarize the possible mechanism.Methods: A systematic review and meta-analysis were conducted to analyze the existing studies on the effects of scutellaria baicalensis on depression in animal models. Briefly, we searched electronic databases including Pubmed and Embase for preclinical trial studies from inception to September 2023. The items in each study were evaluated by two independent reviewers, and meta-analyses were performed on scutellaria baicalensis-induced behavioral changes in the study. Finally, random effects model is used to collect data.Results: A total of 49 studies were identified, and 13 studies were included in the final analysis. They all reported the different antidepressant effects of scutellaria baicalensis and the underlying biological mechanisms. Among the included 13 studies, the results of eight articles SPT[SMD = −2.80, 95%CI(-4.03, -1.57), p < 0.01], the results of the nine articles OFT[SMD = −2.38, 95%CI(-3.53, -1.23), p < 0.01], and the results of two articles NSFT[SMD = −2.98, 95%CI(-3.94, -2.02), p < 0.01] were significantly different from the control group. The risk of bias was moderate in all studies, however, there was a significant heterogeneity among studies.Conclusion: These results preliminarily suggest that scutellaria baicalensis can alleviate depressive behaviors and modulate underlying mechanisms, which is expected to be a promising antidepressant.

Objective: The aim of this study is to assess the postoperative efficacy of the combined administration of dienogest (DNG) and gonadotropin-releasing hormone agonists (GnRH-a) in patients diagnosed with endometriosis (EMS), while acknowledging the extensive use of DNG in the extended therapeutic management of EMS.Methods: In this retrospective study, a cohort of 154 patients who underwent conservative surgical intervention for EMS were scrutinized. The cohort was stratified into two distinct groups based on their prescribed pharmacological regimens. Group A, 70 patients received postoperative oral administration of DNG at a dosage of 2 mg/day, whereas Group B, 84 patients underwent treatment involving 3 to 4 injections of GnRH-a post-surgery, followed by DNG therapy. Parameters assessed included pelvic pain visual analog scale (VAS) scores, quality of life metrics (EHP-5), and the incidence of adverse reactions within both groups.Results: Both groups exhibited sustained low VAS scores following the prescribed treatments. The predominant occurrence of adverse bleeding patterns manifested predominantly within the initial 6 months of the treatment. Notably, Group B demonstrated a significantly diminished of experiencing frequent and irregular bleeding in comparison to the DNG group (20.0% vs. 8.3%, 12.9% vs. 3.6%, p < 0.05). The administration of GnRH-a did not exacerbate the impact on bone health. Subsequent to health promotion interventions, the incidence of weight gain in both groups declined to 7.1% during the 6-month follow-up (p < 0.05). Group B exhibited a 100% satisfaction rate with the treatment, concomitant with a noteworthy reduction in EHP-5 scores (p < 0.05). Patients with deep infiltrating endometriosis (DIE) nodules displayed marginally higher postoperative VAS scores than their non-DIE counterparts (0.89 ± 0.96 vs. 0.49 ± 0.78). However, with sustained medication use, pain scores within the DIE group exhibited a continual decrease, maintaining a low level of 0.29 ± 0.67 at 12 months and beyond.Conclusion: The short-term adjunctive use of GnRH-a prior to DNG treatment postoperatively in patients with EMS proves efficacious in mitigating early adverse bleeding, enhancing patient adherence, and improving overall quality of life. Notably, this therapeutic approach demonstrates favorable safety profiles and is equally effective in patients with DIE.

Climate change is endangering the soil carbon stock of alpine grasslands on the Qinghai-Tibetan Plateau (QTP), but the limited comprehension regarding the mechanisms that sustain carbon storage under hydrothermal changes increases the uncertainty associated with this finding. Here, we examined the relative abundance of soil microbial keystone taxa and their functional potentials, as well as their influence on soil carbon storage with increased precipitation across alpine grasslands on the QTP, China. The findings indicate that alterations in precipitation significantly decreased the relative abundance of the carbon degradation potentials of keystone taxa, such as chemoheterotrophs. The inclusion of keystone taxa and their internal functional potentials in the two best alternative models explained 70% and 63% of the variance in soil organic carbon (SOC) density, respectively. Moreover, we found that changes in chemoheterotrophs had negative effects on SOC density as indicated by a structural equation model, suggesting that some specialized functional potentials of keystone taxa are not conducive to the accumulation of carbon sink. Our study offers valuable insights into the intricate correlation between precipitation-induced alterations in soil microbial keystone taxa and SOC storage, highlighting a rough categorization is difficult to distinguish the hidden threats and the importance of incorporating functional potentials in SOC storage prediction models in response to changing climate.

Olea europaea L., olive tree, has a very important role in the economy of the Mediterranean region, where 93 % of the world's olive oil is produced. This species is well adapted to the environmental conditions of this area, but the increase in the frequency of extreme climatic events, due to climate change, is affecting the yield and quality of olive products. The use of eco-friendly solutions, like plant-beneficial microorganisms, can be a sustainable agronomic tool to improve plant tolerance to stress and boost agricultural production. We aim to unravel the effects of the pre-treatment of olive plants with the bacterium Pseudomonas reactans Ph3R3 on drought tolerance. Young potted olive plants were treated with a solution of P. reactans (soil inoculation) or with distilled water, and then exposed to two watering conditions (well-watered or water deficit). Plant water status, photosynthesis, pigments, carbohydrates, oxidative stress biomarkers, and total antioxidant capacity were evaluated 61 and 191 days after the beginning of the watering treatments. The pre-treatment with P. reactans improved leaf dry biomass production, and soil C and N availability. Moreover, under drought conditions, P. reactans increased leaf water availability, N levels, and the intercellular CO2, leading to improved net CO2 assimilation rate and carbohydrates production. Also, P. reactans activated stress protective strategies (total antioxidant capacity) that helped to control oxidative stress. These data demonstrated that the benefits triggered by P. reactans pre-treatment promoted olive performance and tolerance to drought and could be a promising strategy to improve olive culture sustainability.

Counting and analyzing of blood cells, as well as their subcellular structures, are indispensable for understanding biological processes, studying cell functions, and diagnosing diseases. In this paper, we combine digital holographic microscopy with cell segmentation guided by the Sobel operator using Dice coefficients for automatic threshold selection and aimed to automatic counting and analysis of blood cells in flow and different kinds of cells in the static state. We demonstrate the proposed method with automatic counting and analyzing rat red blood cells (RBCS) flowing in a microfluidic device, extracting quickly and accurately the size, concentration, and dry mass of the sample in a label-free manner. The proposed technique was also demonstrated for automatic segmentation of different cell types, such as COS7 and Siha. This method can help us in blood inspection, providing pathological information in disease diagnosis and treatment.

BackgroundThe synergistic effectiveness of combining immune checkpoint inhibitors with targeted therapies has shown promise in improving the conversion rate for unresectable hepatocellular carcinoma (HCC) patients to a potentially resectable status. However, the efficacy of this approach in the context of HCC with extrahepatic metastasis remains to be conclusively determined.Case presentationWe report a rare case of advanced HCC with extrahepatic metastasis who achieved long-term survival by a combination of systemic therapy (sintilimab and sorafenib) followed by laparoscopic hepatectomy. A 63-year-old man presented at our hospital with discomfort on the right side of his waist. An enlarged right hepatic lobe mass was subsequently revealed by CT scan. The patient’s medical history, including a prior infection with hepatitis B virus, cirrhosis of the liver and an alpha-fetoprotein (AFP) level measuring 41.28 ng/ml substantiated the clinical diagnosis of HCC. On October 30th, 2019, the patient received 200 mg sintilimab intravenously (q3w) plus 200–400 mg BID sorafenib orally, along with antiviral therapy. After six cycles, his disease achieved partial response (PR). On April 26th, 2021, He underwent a laparoscopic hepatectomy. The patient achieved a sustained period of no evidence of disease for 2.5 years and with drug-free survival for 2 years after the resection. His current overall survival is estimated at approximately 4 years.ConclusionsThis case highlights the potential of combining sintilimab and sorafenib in transforming HCC with extrahepatic metastasis into a condition amenable to surgical resection, suggesting that this treatment approach, followed by surgery, may lead to complete remission.

Research on the role of paraprobiotics in ameliorating the pathology of ulcerative colitis and its intestinal homeostatic imbalance is still limited. In this study, we investigated the effects of the anti-inflammatory probiotic HF05 and HF06 derived paraprobiotics 5-PA and 6-PA on mice with ulcerative colitis and their intestinal homeostasis. 5-PA and 6-PA alleviated inflammation, intestinal damage, and weight loss in mice, suppressed the activation of the NF-κB/NLRP3 signaling pathway, and upregulated the expression of intestinal tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the two paraprobiotic regulated the gut microbiota and their metabolic interactions with the host. Specific taxa of gut microbes, including unclassified f_Muribaculaceae, Lactobacillus, Adlercreutzia, and Candidatus_Homeothermus, as well as bile acids and glycerophospholipid metabolites, were closely associated with gut homeostasis. In conclusion, this study confirms the beneficial effects of 5-PA and 6-PA in alleviating ulcerative colitis and promoting intestinal homeostasis.

BackgroundWith the rapid growth of an aging global population and proportion, the prevalence of frailty is constantly increasing. Therefore, finding a frailty assessment tool suitable for clinical application by physicians has become the primary link in the comprehensive management of frailty in elderly patients. This study used the (fr)AGILE scale to investigate the frailty status of elderly patients from internal medicine wards and identified relevant factors that affect the severity of frailty.MethodIn this study, 408 elderly inpatients in internal medicine departments of Qilu Hospital of Shandong University from May 2021 to August 2022 were enrolled as research subjects, and a cross-sectional observational study was conducted. Researchers evaluated the frailty based on the (fr)AGILE scale score. The general condition, past medical history, physical examination, laboratory examination, nutrition control score, intervention and treatment measures and other elderly patient information was collected. Logistic regression analysis was used to analyze the relevant factors that affect the severity of frailty and hospitalization costs.ResultsAccording to the (fr)AGILE scale score, the elderly patients were divided into groups to determine whether they were frail and the severity of the frailty. Among them, 164 patients were in the prefrailty stage, which accounted for 40.2%. There were 188 cases of mild frailty that accounted for 46.1%, and 56 cases of moderate to severe frailty that accounted for 13.7%. Decreased grip strength, elevated white blood cell levels, and low sodium and potassium are independent risk factors affecting the severity of frailty. As the severity of frailty increases, the proportion of sodium, potassium, albumin supplementation as well as anti-infection gradually increases.ConclusionFrailty is a common elderly syndrome with a high incidence among elderly patients in internal medicine departments. The main manifestations of frailty vary with different severity levels. Inflammation, anemia, and poor nutritional status can lead to an increase in the severity of frailty as well as blood hypercoagulability, myocardial damage, and additional supportive interventions. This ultimately leads to prolonged hospitalization and increased hospitalization costs.

Abstract As the prevailing non-volatile memory (NVM), flash memory offers mass data storage at high integration density and low cost. However, due to the ‘speed-retention-endurance’ dilemma, their typical speed is limited to ~microseconds to milliseconds for program and erase operations, restricting their application in scenarios with high-speed data throughput. Here, by adopting metallic 1T-LixMoS2 as edge contact, we show that ultrafast (10–100 ns) and robust (endurance>106 cycles, retention>10 years) memory operation can be simultaneously achieved in a two-dimensional van der Waals heterostructure flash memory with 2H-MoS2 as semiconductor channel. We attribute the superior performance to the gate tunable Schottky barrier at the edge contact, which can facilitate hot carrier injection to the semiconductor channel and subsequent tunneling when compared to a conventional top contact with high density of defects at the metal interface. Our results suggest that contact engineering can become a strategy to further improve the performance of 2D flash memory devices and meet the increasing demands of high speed and reliable data storage.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%. Of PDAC patients, 15%-20% are eligible for radical surgery. Gemcitabine is an important chemotherapeutic agent for patients with PDAC; however, the efficacy of gemcitabine is limited due to resistance. Therefore, reducing gemcitabine resistance is essential for improving survival of patients with PDAC. Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC. Methods: We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment. Then, co-IP, ChIP, ChIP-seq, transcriptome sequencing, and qPCR were used to determine the specific mechanism by which phospholipase D1 (PLD1) confers resistance to gemcitabine. Results: PLD1 combines with nucleophosmin 1 (NPM1) and triggers NPM1 nuclear translocation, where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor (IL7R) expression. Upon interleukin 7 (IL-7) binding, IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein, BCL-2, and induce gemcitabine resistance. The PLD1 inhibitor, Vu0155069, targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells. Conclusions: PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1, further promoting the downstream JAK1/STAT5/Bcl-2 pathway. Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.