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Salvianic acid A (SAA), as the main bioactive component of the traditional Chinese herb Salvia miltiorrhiza, has important application value in the treatment of cardiovascular diseases. In this study, a two-step bioprocess for the preparation of SAA from l-DOPA was developed. In the first step, l-DOPA was transformed to 3,4-dihydroxyphenylalanine (DHPPA) using engineered Escherichia coli cells expressing membrane-bound L-amino acid deaminase from Proteus vulgaris. After that, the unpurified DHPPA was directly converted into SAA by permeabilized recombinant E. coli cells co-expressing d-lactate dehydrogenase from Pediococcus acidilactici and formate dehydrogenase from Mycobacterium vaccae N10. Under optimized conditions, 48.3 mM of SAA could be prepared from 50 mM of l-DOPA, with a yield of 96.6%. Therefore, the bioprocess developed here was not only environmentally friendly, but also exhibited excellent production efficiency and, thus, is promising for industrial SAA production.

Abstract Objectives To develop ultrasound-based radiomics models and a clinical model associated with inflammatory markers for predicting intrahepatic cholangiocarcinoma (ICC) lymph node (LN) metastasis. Both are integrated for enhanced preoperative prediction. Methods This study retrospectively enrolled 156 surgically diagnosed ICC patients. A region of interest (ROI) was manually identified on the ultrasound image of the tumor to extract radiomics features. In the training cohort, we performed a Wilcoxon test to screen for differentially expressed features, and then we used 12 machine learning algorithms to develop 107 models within the cross-validation framework and determine the optimal radiomics model through receiver operating characteristic (ROC) curve analysis. Multivariable logistic regression analysis was used to identify independent risk factors to construct a clinical model. The combined model was established by combining ultrasound-based radiomics and clinical parameters. The Delong test and decision curve analysis (DCA) were used to compare the diagnostic efficacy and clinical utility of different models. Results A total of 1239 radiomics features were extracted from the ROIs of tumors. Among the 107 prediction models, the model (Stepglm + LASSO) utilizing 10 radiomics features ultimately yielded the highest average area under the receiver operating characteristic curve (AUC) of 0.872, with an AUC of 0.916 in the training cohort and 0.827 in the validation cohort. The combined model, which incorporates the optimal radiomics score, clinical N stage, and platelet-to-lymphocyte ratio (PLR), achieved an AUC of 0.882 in the validation cohort, significantly outperforming the clinical model with an AUC of 0.687 (P = 0.009). According to the DCA analysis, the combined model also showed better clinical benefits. Conclusions The combined model incorporating ultrasound-based radiomics features and the PLR marker offers an effective, noninvasive intelligence-assisted tool for preoperative LN metastasis prediction in ICC patients. Clinical trial number Not applicable.

IntroductionFalls are the primary cause of unintentional fatalities among individuals aged 65 and older. Enhancing research on fall prevention among older adults is an urgent priority. Consequently, this study aims to investigate the prevalence and influencing factors of falls among community-dwelling older adults in Guangzhou, China, with a particular emphasis on the impact of family functioning.MethodsWe used a multi-stage stratified cluster random sampling technique to successfully survey 2,399 individuals aged 65 and above across 11 districts in Guangzhou City. Data on sociodemographic characteristics, health and lifestyle factors, and fall incidents were collected through telephone interviews. Chi-square tests, Lasso regression, and logistic regression were utilized to pinpoint fall risk factors. Association rule mining uncovered the relationships between falls and associated variables.ResultsA total of 390 participants reported experiencing falls, the prevalence of falls among older adults was 16.3% (95%CI: 14.82% ~ 17.78%). Logistic regression analysis identified several risk factors for falls among older adults: female [OR = 1.511, 95%CI (1.188–1.922)], age 85 years and older [OR = 2.332, 95%CI (1.447–3.758)], stroke [OR = 1.821, 95%CI (1.038–3.192)], hypoglycemia [OR = 1.639, 95%CI (1.228–2.186)], visual impairment [OR = 1.418, 95%CI (1.097–1.833)], need to be cared for [OR = 1.722, 95%CI (1.339–2.215)], chronic pain [OR = 1.663, 95%CI (1.302–2.124)], and anxiety [OR = 1.725, 95%CI (1.243–2.395)]. In addition, it was shown that a well-functioning family was a protective factor against falls [OR = 0.589, 95%CI (0.44–0.789)].ConclusionThe prevalence of falls among community-dwelling older adults in Guangzhou City was high, and the influencing factors were complex. It is recommended to develop and implement comprehensive intervention measures for high-risk groups, including those who are females, older adults, and suffer from chronic diseases while paying special attention to the care of family members for older adults.

Abstract Background RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. Method The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan–Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis（DCA）analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. Result The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. Conclusion We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.

With the development of aerospace science and technology, requirements for propellants are increasingly high. The thermal decomposition behavior of ammonium perchlorate (AP) directly influences the combustion performance of composite solid propellants. Catalysts play an important role in improving the thermal decomposition behavior of AP. In this study, three novel metal-organic frameworks (MOFs) were prepared using a straightforward method, namely Co[N(CN)2]2 (1; nitrogen content: 43.5%), Cu[N(CN)2]2 (2; nitrogen content: 43.0%), and Pb[N(CN)2]2 (3; nitrogen content: 24.8%). Their crystal structures were characterized and analyzed through single-crystal X-ray diffraction, forming interesting three-dimensional architectures. Moreover, derived composite catalysts under air (4, 6, and 8) or nitrogen (5, 7, and 9) atmosphere were generated by heating MOFs 1, 2, and 3–500 ​°C at a heating rate of 5 ​°C·min−1. The derived catalyst 4 exhibited the best performance. It reduced the decomposition peak temperature of AP by 81.9 ​°C, increased the heat release from 785 ​kJ·g−1 to 1232 ​kJ·g−1, and decreased the apparent activation energy (Ea) of AP from 223 ​kJ·mol−1 to 145 ​kJ·mol−1.

IntroductionAs a developing country with the largest older adult population in the world, strengthening the research on falls among the older adults is undoubtedly an urgent item in China. This study aimed to explore the prevalence and risk factors associated with falls and injury from falls among community-dwelling older adults in Guangzhou, China, particularly focusing on their associations with chronic diseases.MethodsA total of 1,629 participants aged 65 years and above were selected from 11 counties in Guangzhou by the multi-stage stratified random sampling method in 2021. Socio-demographic characteristics, health and lifestyle factors, the status of falls, and injury from falls were measured by structured questionnaires through face-to-face interviews. Chi-square tests and logistic regression analysis were used to identify factors associated with falls and injury from falls. Chord diagrams were used to explore their associations with chronic diseases.ResultsA total of 251 participants (15.41%, 95% CI: 13.98%−17.25%) reported falls, and 162 participants (9.46%, 95% CI:7.72%−11.55%) indicated an injury from falls. Logistic regression analysis showed the results as follows: female patients (adjusted OR = 1.721, 95% CI: 1.681–1.761) aged ≥80 years (1.910, 1.847–1.975), unemployed (1.226, 1.171–1.284), uninsured (1.555, 1.448–1.671), average monthly household income of 2,001–4,000 CNY (1.878, 1.827–1.930), number of services provided by the community health center ≥13 times per year (1.428, 1.383–1.475), illness within 2 weeks (1.633, 1.595–1.672), high-intensity physical activity (2.254, 2.191–2.32), sedentary (1.094, 1.070–1.117), and number of chronic disease illnesses ≥3 (1.930, 1.870–1.993). Meanwhile, those risk factors were also associated with injury from falls. The older adults with medium-intensity physical activity were at lower risk (0.721, 0.705–0.737) of falls and higher risk (1.086, 1.057–1.117) of being injured from falls. Chord diagrams showed the correlations between chronic diseases and falls and injury from falls among community-dwelling older adults in Guangzhou, China.ConclusionThe high prevalence of falls is found among community-dwelling older adults in Guangzhou, China, which is related to multiple factors such as demographic variables, lifestyle, and health status, especially for chronic diseases. Therefore, targeted interventions should be developed and implemented urgently.

Abstract Objective We aimed to observe the clinical effect of single-stage posterior surgery on HIV-positive patients with thoracolumbar tuberculosis. Methods From October 2015 to October 2019, 13 HIV-positive patients with thoracolumbar tuberculosis who underwent single-stage posterior surgery were retrospectively analyzed (observation group), and 13 HIV-negative patients with thoracolumbar tuberculosis who were matched with the gender, age, operative site, and surgical approach during the same period were selected as the control group. Postoperative complications, hemoglobin, albumin, CD4+T lymphocyte count, operative site, operative time, and blood loss were recorded between the two groups. The clinical efficacy was evaluated by the visual analog scale (VAS), American Spinal Injury Association (ASIA) scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kyphotic angle, correction rate of kyphosis, angle loss, and bone graft fusion time. Results In the observation group, 7 patients had postoperative complications, including 1 patient with cerebrospinal fluid leakage, 1 patient with nerve root irritation, 1 patient with an opportunistic infection, and 4 with delayed wound healing. In the control group, 2 patients developed postoperative complications, including 1 with nerve root irritation and 1 with delayed wound healing. There was no statistically significant difference in the incidence of postoperative complications between the two groups (P > 0.05). CD4+T lymphocyte count, hemoglobin, and albumin in HIV-positive patients with postoperative complications were statistically different from those without postoperative complications (P all 0.05). Conclusion Single-stage posterior surgery for HIV-positive patients with thoracolumbar tuberculosis could achieve satisfactory clinical efficacy through comprehensive preoperative evaluation, standardized perioperative antiviral and anti-tuberculosis treatments, and prevention of postoperative complications.

PurposeThis paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated.MethodsSeventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects’ stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects’ serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up.Results(1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p

Abstract Background Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection can lead to a broad spectrum of lung diseases, including infectious diseases and tumors. Recently, with the wide application of bronchoscopes and cytopathology of bronchoalveolar lavage fluid (BALF), the diagnostic efficiency of lung diseases has improved. The present study focuses on analyzing the cytopathologic characteristics of BALF in the diagnosis of HIV/AIDS-related lung disease and comparing the lung disease spectrum between HIV and HIV-uninfected patients. Methods BALF specimens were collected from 2211 patients. Using ThinPrep liquid-based technology, the cytologic smears were prepared by staining with Hematoxylin and Eosin (HE), Gomori's methenamine silver (GMS), and Periodic Acid Schiff (PAS), acid-fast and immunocytochemical (ICC) staining. Real-time PCR was used to detect cytomegalovirus (CMV) and Mycobacterium tuberculosis (M. tuberculosis) in the remaining BALF. PCR-reverse dot hybridization was used for mycobacterial species identification. Results From the 2211 BALF specimens, 1768 (79.96%) were specimens from HIV-infected patients, and 443 (20.04%) were speciments from HIV-uninfected patients. The HIV-infected patients with a median age of 38.5 ± 11.3 years were markedly younger than the HIV-uninfected patients (52.9 ± 14.9 years) (p

Abstract Background Cytomegalovirus (CMV) has been recognized as one of the frequently occurring opportunistic infections (OIs) reported in the patients having human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In addition, it has been identified as the factor leading to gastrointestinal (GI) tract disorder among HIV/AIDS population. CMV exhibits broad cell tropism in different organs. This study evaluated the CMV cell tropism and clinicopathological characteristics of CMV infection in the different GI regions in HIV/AIDS cases. Methods Using nucleic acid in situ hybridization (ISH), CMV was detected in the gastrointestinal mucosal biopsy samples. The paraffin-embedded samples were stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC), respectively. Results A total of 32 HIV/AIDS patients were enrolled in this study. Fourteen of these patients underwent gastroscopy, while the remaining eighteen received colonoscopy. CMV-infected cells were observed at 46 GI sites. Among them, the colon was the region with the highest susceptibility to GI CMV infection (n = 12, 26.1%). The CMV giant cell inclusion bodies were detected in epithelial cells and mesenchymal cells, including histiocytes, smooth muscle cells, fibroblasts, and endothelial cells. In the duodenum, there were markedly more positive epithelial cells than mesenchymal cells (p = 0.033). In contrast, in the esophagus (p = 0.030), cardia (p = 0.003), rectum (p = 0.019), colon (p

Abstract Background Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE. Methods A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service. Results There were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD4 + count ranged from 11 to 159 cells/μl (median 92 cells/μl), and serological HIV viral load 0–989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent. Conclusions The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

Abstract Background Cytomegalovirus (CMV) is among the most common opportunistic infections identified in patients with HIV/AIDS. CMV often targets the colon in such patients. However, the role of regulatory T cells (Tregs) and Programmed death-1 (PD-1) in intestinal CMV infection is unclear. In this study, we evaluate the expression of programmed death -1 (PD-1) and its association with regulatory T cells (Tregs) in patients with HIV/AIDS having CMV colitis. Methods CMV was detected in the intestinal mucosal biopsy samples via nucleic acid in situ hybridization. PD-1, CD4, CD8, and Treg-specific marker as well as the winged-helix transcription factor and forkhead box P3 (FoxP3) were detected by immunohistochemical methods. Results Intestinal CMV diease was identified in 20 out of 195 patients with HIV/AIDS enrolled in our study. CMV was diagnosed microscopically by the presence of giant cell inclusion bodies in epithelial cells, histiocytes, and fibroblasts. Levels of immunoreactive PD-1 detected in mucosal biopsies from patients with HIV/AIDS having CMV colitis were significantly higher than CMV-negative control group (p = 0.023). FoxP3+ cells were detected in the CMV colitis group slight more than that in the control group. CD4+ T lymphocyte counts in the peripheral blood and intestinal mucosal biopsies from CMV colitis group were all notably decreased compared with those with control group (p

Objective: To establish a mouse model of atopic dermatitis (AD) with overgrowth Malassezia globosa. Methods: Eighteen BALB/c mice were randomly divided into the control group, AD group, NS/M group, AD+NS/M group, Oil/M group and AD+Oil/M group, 3 mice per group. AD model of BALB/c mice were established by topical administration of MC903. Fungi overgrowth experimental models were attempted to establish using suspension of M. globosa with olive oil and normal saline as vehicle, respectively. Clinical manifestations and lesion scoring as well as mycological and histopathological changes of each group were evaluated. Scanning and transmission electron microscopy were also used to observe the changes on hair follicle and hair shaft. Results: Compared with AD group, more severe AD-like lesion, obvious hair loss andincreasedlesion scoring (q=5.95, P

Abstract Background Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block. Methods A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori’s methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section. Results The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p

Nicotine contained in traditional cigarettes, hookahs, and e-cigarettes is an important risk factor for cardiovascular disease. Our previous study showed that macroautophagic flux impairment occurred under nicotine stimulation. However, whether nicotine influences mitochondrial dynamics in neonatal rat ventricular myocytes (NRVMs) is unclear. The purpose of this study was to explore the effects and potential mechanism of nicotine on mitophagy, mitochondrial dynamics, apoptosis, and the relationship between these processes in NRVMs. Our results showed that nicotine exposure increased mitochondria-derived superoxide production, decreased mitochondrial membrane potential, and impaired PINK1/Parkin-mediated mitophagic flux in NRVMs. Interestingly, nicotine significantly promoted dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and suppressed mitofusin (MFN)-mediated fusion, which was also observed in the bafilomycin A1-treated group. These results suggest that mitophagic flux impairment may contribute to Drp-1-mediated mitochondrial fission. Finally, nicotine caused excessive mitochondrial fission and contributed to apoptosis, which could be alleviated by mdivi-1, an inhibitor of Drp1. In addition to CTSB, as we previously reported, the enzyme activity of cathepsin L (CTSL) was also decreased in lysosomes after stimulation with nicotine, which may be the main cause of the hindered mitophagic flux induced by nicotine in NRVMs. Pretreatment with Torin 1, which is an inhibitor of mTOR, activated CTSL and ameliorated nicotine-induced mTOR activation and mitophagy impairment, decreased mitochondria-derived superoxide production, and blunted mitochondrial fission and apoptosis. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) or inhibitors of p38 and JNK, which could also alleviate mitophagy impairment, exhibited similar effects as Torin1 on mitochondria. Taken together, our study demonstrated that nicotine treatment may lead to an increase in Drp1-mediated mitochondrial fission by blocking mitophagic flux by weakening the enzyme activity of CTSL and activating the ROS/p38/JNK signaling pathway. Excessive mitochondrial fission induced by nicotine ultimately leads to apoptosis. Torin1 restored the decreased CTSL enzyme activity by removing excessive ROS and alleviated the effects of nicotine on mitophagic flux, mitochondrial dynamics, and apoptosis. These results may provide new evidence on the relationship between mitophagic flux and mitochondrial dynamics and new perspectives on nicotine’s effects on mitochondrial dynamics in cardiomyocytes.

Stenotrophomonas acidaminiphila is an aerobic, glucose non-fermentative, Gram-negative bacterium that been isolated from various environmental sources, particularly aquatic ecosystems. Although resistance to multiple antimicrobial agents has been reported in S. acidaminiphila, the mechanisms are largely unknown. Here, for the first time, we report the complete genome and antimicrobial resistome analysis of a clinical isolate S. acidaminiphila SUNEO which is resistant to sulfamethoxazole. Comparative analysis among closely related strains identified common and strain-specific genes. In particular, comparison with a sulfamethoxazole-sensitive strain identified a mutation within the sulfonamide-binding site of folP in SUNEO, which may reduce the binding affinity of sulfamethoxazole. Selection pressure analysis indicated folP in SUNEO is under purifying selection, which may be owing to long-term administration of sulfonamide against Stenotrophomonas.

AIMS: Invasion and metastasis are major reasons for pancreatic cancer death and identifying signaling molecules that are specifically used in tumor invasion is of great significance. The purpose of this study was to elucidate the role of GEP100 in pancreatic cancer cell invasion and metastasis and the corresponding molecular mechanism. METHODS: Stable cell lines with GEP100 knocked-down were established by transfecting GEP100 shRNA vector into PaTu8988 cells and selected by puromycin. qRT-PCR and Western blot were performed to detect gene expression. Matrigel-invasion assay was used to detect cancer cell invasion in vitro. Liver metastasis in vivo was determined by splenic injection of indicated cell lines followed by spleen resection. Immunofluorescence study was used to detect the intracellular localization of E-cadherin. RESULTS: We found that the expression level of GEP100 protein was closely related to the invasive ability of a panel of 6 different human pancreatic cancer cell lines. Down-regulation of GEP100 in PaTu8988 cells significantly decreased invasive activity by Matrigel invasion assay, without affecting migration, invasion and viability. The inhibited invasive activity was rescued by over-expression of GEP100 cDNA. In vivo study showed that liver metastasis was significantly decreased in the PaTu8988 cells with GEP100 stably knocked-down. In addition, an epithelial-like morphological change, mimicking a mesenchymal to epithelial transition (MET) was induced by GEP100 down-regulation. The expression of E-cadherin protein was increased 2-3 folds accompanied by its redistribution to the cell-cell contacts, while no obvious changes were observed for E-cadherin mRNA. Unexpectedly, the mRNA of Slug was increased by GEP100 knock-down. CONCLUSION: These findings provided important evidence that GEP100 plays a significant role in pancreatic cancer invasion through regulating the expression of E-cadherin and the process of MET, indicating the possibility of it becoming a potential therapeutic target against pancreatic cancer.