Airborne antibiotic resistome from sludge dewatering systems: Mobility, pathogen accessibility, cross-media migration propensity, impacting factors, and risks.

Bioaerosol contamination was considered as a potential health threat in sludge dewatering systems (SDSs), while emission and risk of airborne antibiotic resistome remain largely unclear. Herein, seasonal investigations of fine particulate matter (PM2.5) were conducted using metagenomics-based methods within and around different SDSs, together with an analysis of sewage sludge. Featured with evident seasonality, antibiotic resistance genes (ARGs) in SDS-PM2.5 also possessed greater accumulation, transfer, and pathogen accessibility than those in ambient air PM2.5. Mobile ARGs in SDS-PM2.5 mainly encoded resistance to tetracycline, and most were flanked by integrase. Some pathogenic antibiotic resistant bacteria (PARB), including Enterobacter asburiae, Escherichia coli, Enterococcus faecium, and Staphylococcus aureus, also carried mobile genetic elements in SDS-PM2.5. Dewatering behavior actuated > 50.56% of ARG subtypes and > 42.86% of PARB in sewage sludge to aerosolize into air. Relative humidity, temperature, and PM2.5 concentration collectively drove the evolution of bacterial community and indirectly promoted the antibiotic resistance of SDS-PM2.5. SDS-PM2.5 posed more serious resistome risks than sewage sludge and ambient air PM2.5, and the highest levels were discovered in winter. These findings underline the role of dewatering behavior in facilitating resistome's aerosolization, and the need to mitigate this potential air pollution.

Deletion of Mgat2 in spermatogonia blocks spermatogenesis.

Identifying factors required for spermatogenesis is important for understanding mechanisms of male fertility. Inactivation of either the Mgat1 or Man2a2 gene leads to a block in spermatogenesis causing infertility in male mice. MGAT1 GlcNAc-transferase initiates complex N-glycan synthesis and MAN2A2 mannosidase generates the substrate for MGAT2 GlcNAc-transferase to form a biantennary complex N-glycan. In this paper, we show that conditional deletion of Mgat2 in spermatogonia via Stra8-iCre caused a novel block in spermatogenesis, largely prior to the formation of round spermatids. Mgat2[-/-] germ cells did not bind the lectins Phaseolus vulgaris leucoagglutinin (L-PHA) or Griffonia simplicifolia II (GSA-II), similar to germ cells lacking MGAT1 and complex N-glycans. However, overall spermatogenic defects were distinct in germ cells with deleted Mgat2 versus Mgat1. In addition, RNA-seq analysis at 15 days after birth revealed a unique transcriptomic landscape in Mgat2[-/-] germ cells with genes required for sperm formation and functions being most downregulated. Bioinformatic analyses using the ingenuity pathway analysis (IPA) algorithm identified ERK and AKT as central activities. Western blot analyses of 15-day germ cell lysates confirmed that both AKT and ERK1/2 signaling were increased by loss of MGAT2 in germ cells. By contrast, Mgat1[-/-] germ cells were previously shown to have reduced ERK signaling and unchanged AKT activity. Therefore, since the loss of all complex N-glycans is common to each mutant model, the different immature N-glycans that accumulate in Mgat2[-/-] versus Mgat1[-/-] germ cells are proposed to be the basis of their unique spermatogenic phenotypes.

The association between serum S100ß levels and prognosis in acute stroke patients after intravenous thrombolysis: a multicenter prospective cohort study.

BACKGROUND: S100ß is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100ß and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. METHODS: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100ß levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. RESULTS: A total of 1072 patients were included in the analysis. The highest S100ß levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100ß level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: ß 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: ß 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100ß levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: ß 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: ß 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100ß levels and HT was not significant in either stroke lateralization group. CONCLUSIONS: Serum S100ß levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100ß in judging the degree of disease and predicting prognosis.

Establishment of an Animal Model of Oral Squamous Cell Carcinoma Invading the Mandible.

OBJECTIVE: To establish an animal model of oral squamous cell carcinoma invading the mandible through multi-sample experiments that verified the stability, repeatability, tumorigenicity and mandible destruction rate of the model. METHODS: Oral squamous cell carcinoma cell suspension was injected into the outer side of the mandible through the anterior edge of the masseter muscle of naked mice to observe the tumourforming process. Then, the anatomical, histological and imaging examinations were carried out to determine whether the tumour had invaded the mandible. By comparing the tumour growth of multiple groups of various squamous cell carcinoma cells (CAL27, HN6 and HN30 cells), the changes in body weight and characteristics of tumour formation were compared, and the experience was summarised to further verify the stability, repeatability, tumour formation rate and arch damage rate of the model. RESULTS: The subsequent specimens of tumour-bearing nude mice were validated once the model had been established. In vitro, tumour tissue wrapped around the mandible's tumour-bearing side, and the local texture was tough with no resistance to acupuncture. Haematoxylin and eosin staining revealed that squamous cells were infiltrating the mandible in both the horizontal and sagittal planes. Microcomputed tomography results showed that the mandible on the tumour-bearing side displayed obvious erosion damage. Cell lines with various passage rates clearly had diverse tumour-bearing life cycles. CONCLUSION: This study successfully established an animal model of oral squamous cell carcinoma invasion of the mandible. The model has excellent biological stability, repeatability, tumorigenesis rate and mandible destruction rate.

Spatial characterization and stratification of colorectal adenomas by deep visual proteomics.

Colorectal adenomas (CRAs) are potential precursor lesions to adenocarcinomas, currently classified by morphological features. We aimed to establish a molecular feature-based risk allocation framework toward improved patient stratification. Deep visual proteomics (DVP) is an approach that combines image-based artificial intelligence with automated microdissection and ultra-high sensitive mass spectrometry. Here, we used DVP on formalin-fixed, paraffin-embedded (FFPE) CRA tissues from nine male patients, immunohistologically stained for caudal-type homeobox 2 (CDX2), a protein implicated in colorectal cancer, enabling the characterization of cellular heterogeneity within distinct tissue regions and across patients. DVP identified DMBT1, MARCKS, and CD99 as protein markers linked to recurrence, suggesting their potential for risk assessment. It also detected a metabolic shift to anaerobic glycolysis in cells with high CDX2 expression. Our findings underscore the potential of spatial proteomics to refine early stage detection and contribute to personalized patient management strategies and provided novel insights into metabolic reprogramming.

Exploration of Protease Resources in the Gut of Omnivorous Gryllotalpa orientalis (Orthoptera: Gryllotalpidae).

An insect's gut microbiome is an essential "organ" in their life cycle, playing a crucial role by aiding food digestion and nutrient absorption. This study employed both culture-independent and culture-dependent methods to explore the protease resources present in the gut of the omnivorous insect Gryllotalpa orientalis. The findings revealed that the gut extract of G. orientalis contained a diverse array of proteases, including cysteine proteases, pepsin, serine proteases, and trypsin, as well as some unidentified proteases. Furthermore, the protease gene htpX, derived from gut bacterium Priestia megaterium DX-3, has been cloned and recombinantly expressed. The recombinant DX-3-htpX protease exhibited a 61.9-fold increase in fermentation level compared to the DX-3 protease. This protease was characterized as a neutral, heat-resistant metalloprotease with an M48 peptidase domain, and it was observed that the binding of Ca2+ to the recombinant protease resulted in the formation of the largest active pocket. This study provides technical support for further development and utilization of functional protein resources in insect gut.

scDAPP: a comprehensive single-cell transcriptomics analysis pipeline optimized for cross-group comparison.

Single-cell transcriptomics profiling has increasingly been used to evaluate cross-group (or condition) differences in cell population and cell-type gene expression. This often leads to large datasets with complex experimental designs that need advanced comparative analysis. Concurrently, bioinformatics software and analytic approaches also become more diverse and constantly undergo improvement. Thus, there is an increased need for automated and standardized data processing and analysis pipelines, which should be efficient and flexible too. To address these, we develop the single-cell Differential Analysis and Processing Pipeline (scDAPP), a R-based workflow for comparative analysis of single cell (or nucleus) transcriptomic data between two or more groups and at the levels of single cells or 'pseudobulking' samples. The pipeline automates many steps of pre-processing using data-learnt parameters, uses previously benchmarked software, and generates comprehensive intermediate data and final results that are valuable for both beginners and experts of scRNA-seq analysis. Moreover, the analytic reports, augmented by extensive data visualization, increase the transparency of computational analysis and parameter choices, while facilitate users to go seamlessly from raw data to biological interpretation. scDAPP is freely available under the MIT license, with source code, documentation and sample data at the GitHub (https://github.com/bioinfoDZ/scDAPP).

The Effect of Cosmetic Makeup on Body Imagery and Anxiety and Depression in Patients Undergoing Postoperative Chemotherapy for Breast Cancer: A Randomized Controlled Study.

Purpose: The objective was to compare the body images of breast cancer patients undergoing postoperative chemotherapy and the varying degrees of their anxiety and depression. The comparison involved those who received four consecutive cycles of cosmetic makeup and those who did not. Patients and Methods: Seventy-four breast cancer patients receiving postoperative chemotherapy were randomly assigned to either the control group or the intervention group. The control group received usual care, while the intervention group received four consecutive cycles of chemotherapy along with cosmetic makeup intervention on top of usual care. The intervention was carried out on the first day after the completion of each chemotherapy cycle. Assessments were made before the first intervention and 1 month after the fourth intervention using the Hospital Anxiety and Depression Scale and the Scale of Body Imagery. Results: After four cycles of intervention, significant differences emerged between the intervention and control groups regarding anxiety, depression, and body imagery. Additionally, within the intervention group, notable changes in these aspects were observed over time. Conclusion: The results showed that cosmetic interventions can effectively reduce the level of anxiety and depression of breast cancer patients receiving postoperative chemotherapy and effectively improve the body imagery of patients.

Liraglutide alleviates ferroptosis in renal ischemia reperfusion injury via inhibiting macrophage extracellular trap formation.

BACKGROUND AND PURPOSE: Renal transplantation and other conditions with transiently reduced blood flow is major cause of renal ischemia/reperfusion injury (RIRI), a therapeutic challenge clinically. This study investigated the role of liraglutide in ferroptosis-associated RIRI via macrophage extracellular traps (METs). METHODS: Animal model with RIRI was established in C57BL/6J mice. A total of 72 C57BL/6J mice were used with 8 mice per group. Primary tubular epithelium was co-culture with RAW264.7 under hypoxia/reoxygenation (H/R) condition to mimic in vitro. Liraglutide was administrated into mice and cells. Extracellular DNA, neutrophil elastase and myeloperoxidase in serum and supernatant of cell medium were collected for measuring METs. F4/80 and citH3 were labeled to show METs. RESULTS: Liraglutide relieved RIRI and ferroptosis in vivo, and inhibited renal I/R-induced METs both in vivo and in vitro. F4/80 and citrullinated histone H3 (citH3) were highly co-localized after RIRI. Liraglutide attenuated the co-localization of citH3 and F4/80. Expressions of M2 markers were enhanced whereas these of M1 markers suppressed during liraglutide treatment in RIRI. Phosphorylation of signal transducer and activator of transcription (STAT)1, 3 and 6 were increased in RIRI mice and H/R-induced RAW264.7. However, liraglutide decreased phosphorylation of STAT1 and increased phosphorylation of STAT3 and STAT6. STAT3/6 inhibition reversed liraglutide-inhibited M1 polarization, extracellular traps and ferroptosis. CONCLUSION: Liraglutide inhibited ferroptosis-induced renal dysfunction since it skewed macrophage polarization into M2 phenotype that interfered the formation of extracellular traps based on STAT3/6 pathway during RIRI. Liraglutide was proposed to be used for RIRI clinical treatment.

A century-long China homogenized daily surface air temperature dataset (CUG-CMA CHDT).

Daily meteorological observation data of the early period (pre-1950) were critically important for investigating the long-term trends and multi-decadal scale variability of extreme climate events. The high-resolution surface air temperature (SAT) data for time period before 1950 are lacking in China. We extended the SAT observations of China back to 1840 through developing a pre-1950 daily SAT dataset. The early-period daily SAT were manually corrected for the input and clerical errors, and then according to the length or coverage of time, the main series for each of the cities was determined. The observation time system of unknown sites was determined by the minimum difference method. After these operations, the data of all sites were unified into the same format. By using the ridge regressions established based on data from modern reference stations, the missing maximum temperature (Tmax) and minimum temperature (Tmin) were interpolated. The early-period data were combined with modern data to form the long-term daily SAT dataset of 1840-2020 in China. RHtest software was used to detect and adjust the inhomogeneities in the station data series. Finally, the century-long homogenized daily SAT dataset including 45 key city stations in China was obtained. Among the stations, there are 20 stations with observation record more than one hundred years. The length of temperature observation series of 17 stations is between 80 and 100 years. The series length of the remaining 7 stations is between 68 and 80 years. Finally, the angular distance weighting (ADW) method was used to interpolate the data into grid products, and the grid size is 2.5 ° × 2.5 °. The dataset was named CUG-CMA CHDT, which is applicable in monitoring, studies and assessments of regional extreme temperature change and variability in China.

The impact of postoperative adjuvant therapy on EGFR-mutated stage IA lung adenocarcinoma with micropapillary pathological subtypes.

BACKGROUND: Micropapillary (MPP) adenocarcinoma is considered one of the most aggressive pathological types of lung adenocarcinoma (LADC). This retrospective study aimed to evaluate the prognostic significance and benefit of postoperative adjuvant therapy (PAT) in stage IA LADC patients with different proportions of MPP components. MATERIALS AND METHODS: We retrospectively examined clinical stage IA LADC patients who underwent surgical resection between August 2012 and December 2019. In terms of the proportion of MPP components (TPM), the tumors were reclassified into three categories: MPP patterns absent (TPMN); low proportions of MPP components (TPML); and high proportions of MPP components (TPMH). The dates of recurrence and metastasis were identified based on physical examinations and were confirmed by histopathological examination. RESULTS: Overall, 505 (TPMN, n = 375; TPML, n = 92; TPMH, n = 38) patients harboring EGFR mutations were enrolled in the study. Male sex (P = 0.044), high pathological stage (P < 0.001), and MPP pathological subtype (P < 0.001) were more frequent in the TPM-positive (TPMP) group than in the TPM-negative (TPMN) group. Five-year disease-free survival (DFS) rates were significantly lower in the TPMP group than in the TPMN group (84.5% vs. 93.4%, P = 0.006). In addition, patients with high proportions (greater than 10%) of MPP components had worse overall survival (OS) (91.0% vs. 98.9%, P = 0.025) than those with low proportions (5%≤ TPM ≤ 10%). However, postoperative EGFR tyrosine kinase inhibitors (TKIs) or adjuvant chemotherapy (ACT) cannot improve DFS and OS between EGFR-mutated patients with different proportions of MPP components. CONCLUSION: MPP was related to earlier recurrence and shortened survival time, even in stage IA. Further research needs a larger sample size to clarify that EGFR-mutated stage IA patients with MPP components obtain survival benefits from adjuvant therapy.

Delay the progression of glucocorticoid-induced osteoporosis: Fraxin targets ferroptosis via the Nrf2/GPX4 pathway.

Glucocorticoid-induced osteoporosis (GIOP) commonly accelerates bone loss, increasing the risk of fractures and osteonecrosis more significantly than traditional menopausal osteoporosis. The extracellular environment influenced by glucocorticoids heightens fracture and osteonecrosis risks. Fraxin (Fra), a key component of the traditional Chinese herbal remedy Cortex Fraxini, is known for its wide-ranging pharmacological effects, but its impact on GIOP remains unexplored. This investigation aims to delineate the effects and underlying mechanisms of Fra in combating dexamethasone (Dex)-induced ferroptosis and GIOP. We established a mouse model of GIOP via intraperitoneal injections of Dex and cultured osteoblasts with Dex treatment for in vitro analysis. We evaluated the impact of Fra on Dex-treated osteoblasts through assays such as C11-BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses via Western blot and immunofluorescence. The influence of Fra on bone microarchitecture of GIOP in mice was assessed using microcomputerized tomography, hematoxylin and eosin staining, double-labeling with Calcein-Alizarin Red S, and immunohistochemistry at imaging and histological levels. Based on our data, Fra prevented Dex-induced ferroptosis and bone loss. In vitro, glutathione levels increased and malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species decreased. Fra treatment also increases nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and COL1A1 expression and promotes bone formation. To delve deeper into the mechanism, the findings revealed that Fra triggered the activation of Nrf2/GPX4 signaling. Moreover, the use of siRNA-Nrf2 blocked the beneficial effect of Fra in osteoblasts cultivated with Dex. Fra effectively combats GIOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis.

Immune checkpoint gene signature assesses immune infiltration profiles in bladder cancer and identifies KRT23 as an immunotherapeutic target.

BACKGROUND: In the past few decades, researchers have made promising progress, including the development of immune checkpoint inhibitors (ICIs) in the therapy of bladder cancer (BLCA). Existing studies mainly focus on single immune checkpoint inhibitors but lack relevant studies on the gene expression profiles of multiple immune checkpoints. METHODS: RNA-sequencing profiling data and clinical information of BLCA patients and normal human bladder samples were acquired from the Cancer Genome Atlas and Gene Expression Omnibus databases and analyzed to identify different expression profiles of immune checkpoint genes (ICGs) after consensus clustering analysis. Based on the 526 intersecting differentially expressed genes, the LASSO Cox regression analysis was utilized to construct the ICG signature. RESULTS: According to the expression of ICGs, BLCA patients were divided into three subtypes with different phenotypic and mechanistic characteristics. Furthermore, the developed ICG signature were independent predictors of outcome in BLCA patients, and was correlated with the immune infiltration, the expression of ICGs and chemotherapeutic effect. CONCLUSIONS: This study systematically and comprehensively analyzed the expression profile of immune checkpoint genes, and established the ICG signature to investigate the differences in ICGs expression and tumor immune microenvironment, which will help risk stratification and accelerate precision medicine. Finally, we identified KRT23 as the most critical model gene, and highlighted KRT23 as a potential target to enhance immunotherapy against BLCA.

Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage: A case report.

BACKGROUND: Programmed cell death 1 (PD-1) inhibitors are immune checkpoint inhibitors (ICI) that have demonstrated significant efficacy in treating various advanced malignant tumors. While most patients tolerate treatment well, several adverse drug reactions, such as fatigue, myelosuppression, and ICI-associated colitis, have been reported. CASE SUMMARY: This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab (a PD-1 inhibitor) for six months. The treatment led to repeated life-threatening lower gastrointestinal hemorrhage. The patient received infliximab, vedolizumab, and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal bleeding. Currently, postoperative gastrointestinal bleeding has stopped, the patient's stool has turned yellow, and his full blood cell count has returned to normal. CONCLUSION: This case highlights the necessity of early identification, timely and adequate treatment of ICI-related colitis, and rapid escalation to achieve the goal of improving prognosis.

The impact of diabetes, hypercholesterolemia, and low-density lipoprotein (LDL) on the survival of cervical cancer patients.

BACKGROUND: Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia and diabetes, on cancer progression, increased mortality, and patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate the relationships between metabolic disorders, including dyslipidemia, dysglycemia, and metabolic syndrome, and survival in patients with cervical cancer. METHODS: We retrospectively analyzed demographic information, clinical characteristics, and metabolic health indicators of patients with cervical cancer. Patients were categorized into groups based on specific metabolic conditions: high triglyceride, high low-density lipoprotein, high cholesterol, and diabetes groups. Additionally, the presence of metabolic syndrome and other metabolic comorbidities was recorded. The log-rank test was used to compare survival rates between different patient groups and identify associated risk factors. Survival curves generated via the Cox proportional hazards model were used to evaluate the associations between metabolic parameters and survival. RESULTS: The Cox proportional hazards model was used to analyze data from 840 patients with cervical cancer between 28 and 72 years old who underwent surgery. The hazard ratio (HR) of mortality was 1.804 (95% CI 1.394-2.333, p < 0.001) in the high-density lipoprotein group, 0.758 (95% CI 0.558 to 1.030, p < 0.001) in the high-triglyceride group, 1.794 (95% CI 1.304-2.470, p < 0.001) in the high low-density lipoprotein group, and 0.011 (95% CI 0.005-0.025, p < 0.001) in the diabetes group. These factors were significantly associated with reduced survival in patients with cervical cancer, and these associations persisted after adjusting for age, cancer stage, treatment type, and the presence of metabolic syndrome or other comorbidities. CONCLUSION: This study highlights the importance of metabolic health and the significance of controlling metabolic disorders, including hyperlipidemia, diabetes, and metabolic syndrome, to improve survival outcomes in patients with cervical cancer. Future research should explore the impact of managing multiple metabolic conditions on the prognosis of these patients.

Screening and Identification of Protease-Producing Microorganisms in the Gut of Gryllotalpa orientalis (Orthoptera: Gryllotalpidae).

The insect gut harbors a diverse array of functional microorganisms that warrant further exploration and utilization. However, there is currently a paucity of research reports on the discovery of protease-producing microorganisms with industrial application value in the gut. Here, we employed microbial culturing to screen and identify the protease-producing microorganisms in the gut extract of Gryllotalpa orientalis. Based on morphological, physiological, and biochemical characterization, 16S rRNA sequencing, as well as ANI and dDDH values of whole genome, the protease-producing strains isolated from the insect gut were identified as Priestia aryahattai DBM-1 and DX-4, P. megaterium DX-3, and Serratia surfactantfaciens DBM-5. According to whole-genome analysis, strain DBM-5, which exhibited the highest enzyme activity, possesses abundant membrane transport genes and carbohydrate metabolism enzymes. In contrast, strains DX-3 and DX-4 not only have the ability to hydrolyze proteins but also demonstrate the capability to hydrolyze plant materials. Furthermore, strains that are closely related tend to have similar metabolic product gene clusters in their genomes. The screening and identification of protease resources are essential for the subsequent development and utilization of gut functional microorganisms and genetic resources in insects.

Targeted small molecule therapy and inhibitors for lymphoma.

Lymphoma, a blood tumor, has become the ninth most common cancer in the world in 2020. Targeted inhibition is one of the important treatments for lymphoma. At present, there are many kinds of targeted drugs for the treatment of lymphoma. Studies have shown that Histone deacetylase, Bruton's tyrosine kinase and phosphoinositide 3-kinase all play an important role in the occurrence and development of tumors and become important and promising inhibitory targets. This article mainly expounds the important role of these target protein in tumors, and introduces the mechanism of action, structure-activity relationship and clinical research of listed small molecule inhibitors of these targets, hoping to provide new ideas for the treatment of lymphoma.

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Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

A comparison of different intensified upstream processes highlighting the advantage of WuXi Biologics' Ultra-high Productivity platform (WuXiUPTM) in improved product quality and purification yield.

WuXiUPTM, WuXi Biologics' Ultra-high Productivity platform, is an intensified and integrated continuous bioprocess platform developed for production of various biologics including monoclonal antibodies, fusion proteins, and bispecific antibodies. This process technology platform has manifested its remarkable capability in boosting the volumetric productivity of various biologics and has been implemented for large-scale clinical material productions. In this paper, case studies of the production of different pharmaceutical proteins using two high-producing and intensified culture modes of WuXiUPTM and the concentrated fed-batch (CFB), as well as the traditional fed-batch (TFB) are discussed from the perspectives of cell growth, productivity, and protein quality. Both WuXiUPTM and CFB outperformed TFB regarding volumetric productivity. Additionally, distinctive advantages in product quality profiles in the WuXiUPTM process, such as reduced acidic charge variants and fragmentation, are revealed. Therefore, a simplified downstream purification process with only two chromatographic steps can be developed to deliver the target product at a satisfactory purity and an extremely-high yield.

Differential short-term and long-term metabolic and cytokine responses to infection of severe fever with thrombocytopenia syndrome virus.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a wide geographic distribution. The primary clinical manifestations of SFTS are fever and thrombocytopenia, with multiorgan failure being the leading cause of death. While most patients recover with treatment, little is known about the potential long-term metabolic effects of SFTSV infection. OBJECTIVES: This study aimed to shed light on dysregulated metabolic pathways and cytokine responses following SFTSV infection, which pose significant risks to the short-term and long-term health of affected individuals. METHODS: Fourteen laboratory-confirmed clinical SFTS cases and thirty-eight healthy controls including 18 SFTSV IgG-positive and 20 IgG-negative individuals were recruited from Taizhou city of Zhejiang province, Eastern China. Inclusion criteria of healthy controls included residing in the study area for at least one year, absence of fever or other symptoms in the past two weeks, and no history of SFTS diagnosis. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to obtain the relative abundance of plasma metabolites. Short-term metabolites refer to transient alterations present only during SFTSV infection, while long-term metabolites persistently deviate from normal levels even after recovery from SFTSV infection. Additionally, the concentrations of 12 cytokines were quantified through fluorescence intensity measurements. Differential metabolites were screened using orthogonal projections to latent structures discriminant analysis (OPLS-DA) and the Wilcoxon rank test. Metabolic pathway analysis was performed using MetaboAnalyst. Between-group differences of metabolites and cytokines were examined using the Wilcoxon rank test. Correlation matrices between identified metabolites and cytokines were analyzed using Spearman's method. RESULTS AND CONCLUSIONS: We screened 122 long-term metabolites and 108 short-term metabolites by analytical comparisons and analyzed their correlations with 12 cytokines. Glycerophospholipid metabolism (GPL) was identified as a significant short-term metabolic pathway suggesting that the activation of GPL might be linked to the self-replication of SFTSV, whereas pentose phosphate pathway and alanine, aspartate, and glutamate metabolism were indicated as significant long-term metabolic pathways playing a role in combating long-standing oxidative stress in the patients. Furthermore, our study suggests a new perspective that α-ketoglutarate could serve as a dietary supplement to protect recovering SFTS patients.