Screening antimicrobial peptides and probiotics using multiple deep learning and directed evolution strategies.

Owing to their limited accuracy and narrow applicability, current antimicrobial peptide (AMP) prediction models face obstacles in industrial application. To address these limitations, we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning (COMDEL) algorithms, coupled with high-throughput AMP screening method, finally reaching an accuracy of 94.8% in test and 88% in experiment verification, surpassing other state-of-the-art models. In conjunction with COMDEL, we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro, ultimately increasing AMPs yields to a range of 0.5-2.1 g/L within hours. Moreover, by multi-omics analysis using COMDEL, we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics. Following this, we developed a microdroplet sorting approach and successfully screened three L. plantarum mutants, each showing a twofold increase in antimicrobial ability, underscoring their substantial industrial application values.

Wastewater treatment plant effluents increase the global warming potential in a subtropical urbanized river.

Rivers play a pivotal role in global carbon (C) and nitrogen (N) biogeochemical cycles. Urbanized rivers are significant hotspots of greenhouse gases (GHGs, N2O, CO2 and CH4) emissions. This study examined the GHGs distributions in the Guanxun River, an effluents-receiving subtropical urbanized river, as well as the key environmental factors and processes affecting the pattern and emission characteristics of GHGs. Dissolved N2O, CO2, and CH4 concentrations reached 228.0 nmol L-1, 0.44 mmol L-1, and 5.2 µmol L-1 during the wet period, and 929.8 nmol L-1, 0.7 mmol L-1, and 4.6 µmol L-1 during the dry period, respectively. Effluents inputs increased C and N loadings, reduced C/N ratios, and promoted further methanogenesis and N2O production dominated by incomplete denitrification after the outfall. Increased urbanization in the far downstream, high hydraulic residence time, low DO and high organic C environment promoted methanogenesis. The strong CH4 oxidation and methanogenic reactions inhibited by the effluents combined to suppress CH4 emissions in downstream near the outfall, and the process also contributed to CO2 production. The carbon fixation downstream from the outfall were inhibited by effluents. Ultimately, it promoted CO2 emissions downstream from the outfall. The continuous C, N, and chlorine inputs maintained the high saturation and production potential of GHGs, and altered microbial community structure and functional genes abundance. Ultimately, the global warming potential downstream increased by 186 % and 84 % during wet and dry periods on the 20-year scale, and increased by 91 % and 49 % during wet and dry periods on the 100-year scale, respectively, compared with upstream from the outfall. In urbanized rivers with sufficient C and N source supply from WWTP effluents, the large effluent equivalently transformed the natural water within the channel into a subsequent "reactor". Furthermore, the IPCC recommended EF5r values appear to underestimate the N2O emission potential of urbanized rivers with high pollution loading that receiving WWTP effluents. The findings of this study might aid the development of effective strategies for mitigating global climate change.

Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis and Increases Overall Survival of Mice-Bearing Lung Cancers.

AIM: Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. METHODS: The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. RESULTS: Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/ß-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. CONCLUSION: Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/ß- catenin pathway.

Extract of Nanhaia speciosa J. Compton & Schrire alleviates LPS-induced acute lung injury via the NF-κB/Nrf2/AQPs pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Nanhaia speciosas J. Compton & Schrire (the name Nanhaia speciosas J. Compton & Schrire has been accepted by the World Checklist of Vascular Plants https://www.worldfloraonline.org/taxon/wfo-0001444004) is a traditional Zhuang medicine that have been widely used for centuries. It has been used in the treatment of lung inflammation, tuberculosis, rheumatic pain, lumbar muscle strain, and various other ailments, such as chronic hepatitis, menoxenia, leukorrhea, and injuries. In addition, N. speciosa has also been used to treat acute lung injury (ALI). AIM OF THE STUDY: The objective of this study was to conduct a comparative analysis of the effects of various constituents present in N. speciosas extract (NSE) on ALI and the related mechanisms while also elucidating the potential active monomeric components. MATERIALS AND METHODS: NSE was extracted using an AB-8 macroporous resin column, and five fractions (Fr. 0%, 25%, 50%, 75% and 95%) were obtained. The anti-inflammatory and antioxidant capacities of the five fractions were evaluated in an A549 cell-based in vitro model, with the aim of evaluating their potential therapeutic effects. The anti-inflammatory and antioxidant capacities of NSE were assessed in a murine model of ALI induced by intratracheal injection of LPS. We utilized an in vitro model to analyse the critical molecular mechanisms through which NSE ameliorates ALI. The chemical composition of the optimal fraction was analysed and confirmed using UHPLC/MS. RESULTS: Different fractions (especially Fr. 75%) significantly reduced inflammation and oxidative stress in A549 cells. Fr.75% abrogated LPS-induced pathological alterations and decreased the lung W/D ratio, total protein concentration in BALF, and the levels of the proinflammatory factors TNF-α, IL-6, and IL-1ß. Moreover, Fr.75% reduced MPO and MDA concentrations and elevated SOD and GSH concentrations in pulmonary tissues. Additionally, it decreased the pulmonary tissue inflammation caused by LPS by downregulating the expression of p-NF-κB p65 and upregulating the expression of Nrf2, AQP1 and AQP5. Fr. 75% decreased p-NF-κB p65 protein levels; increased Keap1, Nrf2, HO-1, NQO1, AQP1 and AQP5 protein levels; and promoted the entry of Nrf2 into the nucleus. After UHPLC/MS analysis was conducted, the flavonoid Maackiain was determined to potentially play a pivotal role in this process. CONCLUSION: Fr.75% alleviates ALI by regulating the NF-κB/Nrf2/AQPs signalling pathway. The flavonoid Maackiain may also play an important role in this process. Overall, N. speciosas may be a potential therapeutic agent for the prevention and treatment of ALI.

Cylindrical HPIII-SbIII-Templated Five-Layer Polyoxotungstate with Conspicuous Photochromism Triggered by UV or Visible Light.

The heteroanion (HA) component plays an important role in the templating of heteropolyoxometalate (HPA) structures, but polyoxometalates (POMs) formed from two different templates are rarely reported. Herein, we present a five-layer POM [H2N(CH3)2]14{[(HPO3)4W6O10][HPSbW15O54]2}·16H2O (1) prepared by two kinds of different HA templates. The multilayer heteropolyanion {[(HPO3)4W6O10][HPSbW15O54]2}14- in 1 consists of two trivacant diheteroatom-templated ([HPO3]2- and [SbO3]3-) [HPSbW15O54]11- subunits linked by one unusual [(HPO3)4W6O10]8+ subcluster via twelve corner-sharing oxygen atoms. Compound 1 was systematically characterized by IR, UV, PXRD, TGA, XPS, and Raman spectra. Compound 1 exhibits good photochromism under UV irradiation with a half-life (t1/2) of 42.5 s, and it also exhibits noteworthy photochromism under visible light irradiation with a half-life (t1/2) of 157.2 s. The possible photochromic mechanism is proposed and verified by the experimental results.

Vertical Barrier Heterostructures for Reliable and High-Performance Self-Powered Infrared Detection.

With their fascinating properties, emerging two-dimensional (2D) materials offer innovative ways to prepare high-performance infrared (IR) detectors. However, the current performance of 2D IR photodetectors is still below the requirements for practical application owing to the severe interfacial recombination, sharply raised contact resistance, and deteriorated metal conductivity at nanoscale. Here, we introduce a vertical barrier heterojunction with a structure of PtSe2/GaAs that combines the excellent optoelectronic properties of transition metal sulfides with topological semi-metals, which allows for an adjustable bandgap and high carrier mobility. The heterojunction was fabricated using the wet transfer method. The heterostructures show significant rectification behaviors and photovoltaic effects, which allow it to operate as a self-driven photodetector at zero bias. The photoresponse parameters at 850 nm with zero bias voltage are 67.2 mA W-1, 6.7 × 1012 Jones, 9.8%, 3.8 × 105, 164 µs, and 198 µs for the responsivity, specific detectivity, external quantum efficiency, Ilight/Idark ratio, rise time, and fall time, respectively. Moreover, the heterojunction is highly sensitive to a wide spectral band from ultraviolet to near-infrared (360-1550 nm). At the same time, this heterostructure demonstrates significant potential for applications in IR polarized light detection and room-temperature high-resolution IR imaging. The excellent properties of the heterojunction make it well-suited for high-performance, self-powered IR detection.

Multi-omics insight into the metabolic and cellular characteristics in the pathogenesis of hypothyroidism.

While circulating metabolites and immune system have been increasingly linked to hypothyroidism risk, the causality underlying these associations remains largely uninterrogated. We used Mendelian randomization to identified putative causal traits for hypothyroidism via integrating omics data. Briefly, we utilized 1180 plasma metabolites and 731 immune cells traits as exposures to identify putatively causal traits for hypothyroidism in the discovery (40,926 cases) and replication cohorts (14,871 cases). By combining MR results from two large-scale cohorts, we ultimately identified 21 putatively causal traits, including five plasma metabolites and 16 immune cell traits. CD3 on CD28+ CD4+ T cell and 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (p-16:0/18:1) demonstrated the most pronounced positive and negative associations with hypothyroidism risk, respectively. The odds ratio and 95% confidence interval were 1.09 (1.07, 1.12) and 0.81 (0.75, 0.87), respectively. No evidence of horizontal pleiotropy, heterogeneity among instrumental variables or reverse causation were found for these 21 significant associations. Our study elucidates key metabolites and immune cell traits associated with hypothyroidism. These findings provide new insights into the etiology and potential therapeutic targets for hypothyroidism.

Chemical coverage of human biological pathways.

Chemical probes and chemogenomic compounds are valuable tools to link gene to phenotype, explore human biology, and uncover novel targets for precision medicine. The mission of the Target 2035 initiative is to discover chemical tools for all human proteins by the year 2035. Here, we draw a landscape of the current chemical coverage of human biological pathways. Although available chemical tools target only 3% of the human proteome, they already cover 53% of human biological pathways and represent a versatile toolkit to dissect a vast portion of human biology. Pathways targeted by existing drugs may be enriched in unknown but valid drug targets and could be prioritized in future Target 2035 efforts.

Reporting tumor genomic test results to SEER registries via linkages.

BACKGROUND: Precision medicine has become a mainstay of cancer care in recent years. The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program has been an authoritative source of cancer statistics and data since 1973. However, tumor genomic information has not been adequately captured in the cancer surveillance data, which impedes population-based research on molecular subtypes. To address this, the SEER Program has developed and implemented a centralized process to link SEER registries' tumor cases with genomic test results that are provided by molecular laboratories to the registries. METHODS: Data linkages were carried out following operating procedures for centralized linkages established by the SEER Program. The linkages used Match*Pro, a probabilistic linkage software, and were facilitated by the registries' trusted third party (an honest broker). The SEER registries provide to NCI limited datasets that undergo preliminary evaluation prior to their release to the research community. RESULTS: Recently conducted genomic linkages included OncotypeDX Breast Recurrence Score, OncotypeDX Breast Ductal Carcinoma in Situ, OncotypeDX Genomic Prostate Score, Decipher Prostate Genomic Classifier, DecisionDX Uveal Melanoma, DecisionDX Preferentially Expressed Antigen in Melanoma, DecisionDX Melanoma, and germline tests results in Georgia and California SEER registries. CONCLUSIONS: The linkages of cancer cases from SEER registries with genomic test results obtained from molecular laboratories offer an effective approach for data collection in cancer surveillance. By providing de-identified data to the research community, the NCI's SEER Program enables scientists to investigate numerous research inquiries.

Prostate cancer disparities in clinical and survival patterns among Black and Latino patients considering nativity: findings from the California Cancer Registry.

BACKGROUND: We investigated clinical characteristics and prostate cancer (PCa) survival patterns among Latino patients considering nativity compared to non-Latino Black (NLB) and non-Latino White (NLW) patients. METHODS: We used data from the California Cancer Registry (1995-2021), which included 347,540 NLW, 50,032 NLB, and 75,238 Latino PCa patients. Frequencies of sociodemographic and clinical variables were assessed with Chi-square tests. Multivariable regression models were fitted to evaluate determinants of treatment reception, Gleason upgrade, and survival differences. Exploratory analyses were conducted grouping Latino cases into US-born and non-US-born by country-of-origin. RESULTS: Compared to NLW, NLB cases had the greatest proportion of younger patients, whereas non-US-born Latino patients had the greatest proportion of low socio-economic status and uninsured patients. Non-US-born Latinos showed greater proportion of diagnoses completed with <6 core biopsies, Gleason >8, stage IV tumors and metastasis. Multivariable analyses showed that compared to NLW, Latino patients were as likely to receive treatment, whereas NLB cases were less likely (OR = 0.81, 95% CI: 0.67-0.98, p = 0.029). Compared to NLW, Non-US-born Latino cases were less likely to die of PCa (HR = 0.78; 95% CI = 0.64-0.94, p=0.011), with no difference reported for NLB cases. CONCLUSIONS: Considering sociodemographic and clinical characteristics, non-US-born Latino PCa patients had better survival than NLW. This highlights the need to identify key determinants of these survival differences, and the importance of sociodemographic and clinical determinants in survival disparities. IMPACT: Our study emphasizes the importance of considering nativity among Latino patients to understand PCa disparities and outcomes in this population.

Clinically significant changes in anal sphincter hiatal area in patients with gestational diabetes mellitus and pelvic organ prolapse.

BACKGROUND: The prevalence of pelvic organ prolapse (POP) increases with age and parity. Specifically, the prevalence of POP among women aged 20 to 39 is 9.7%, while it rises to 49% among women over 80 years old. Additionally, as the number of deliveries increases, the prevalence of POP also rises accordingly, with a rate of 12.8% for women with one delivery history, 18.7% for those with two deliveries, and 24.6% for women with three or more deliveries. It causes immense suffering for pregnant women. AIM: To evaluate the relationship between the levator ani muscle's hiatus (LH) area and POP in patients with gestational diabetes mellitus (GDM) using perineal ultra-sound. METHODS: The study cohort comprised 104 patients aged 29.8 ± 3.7 years who sought medical care at our institution between January 2021 and June 2023. All were singleton pregnancies consisting of 75 primiparas and 29 multiparas, with an average parity of 1.7 ± 0.5. According to the POP diagnostic criteria, the 104 subjects were divided into two groups with 52 members each: POP group (patients with GDM combined with POP) and non-POP group (patients with GDM without POP). Perineal ultrasound was used to measure differences in the anteroposterior diameter, transverse diameter, and LH area. Receiver operating characteristic curves were drawn to determine the optimal cutoff values for the LH anteroposterior diameter, transverse diameter, and area for diagnosing POP. RESULTS: Statistically significant increase in the LH area, anteroposterior diameter, and lateral diameter were observed in the POP group compared with the non-POP group (P < 0.05). Both groups exhibited markedly elevated incidence rates of macrosomia and stress urinary incontinence. For the POP group, the area under the curve (AUC) for the LH area was 0.906 with a 95% confidence interval (CI): 0.824-0.988. The optimal cutoff was 13.54cm², demonstrating a sensitivity of 83.2% and a specificity of 64.4%. The AUC for the anteroposterior diameter reached 0.836 with a 95%CI: 0.729-0.943. The optimal cutoff was 5.53 cm with a sensitivity of 64.2% and a specificity of 73.4%. For the lateral diameter, its AUC was 0.568 with a 95%CI: 0.407-0.729. The optimal cutoff was 4.67 cm, displaying a sensitivity of 65.9% and a specificity of 69.3%. Logistic regression analysis unveiled that age, body weight, number of childbirths, total number of pregnancies, and gestational weight gain constituted the independent risk factors for the cooccurrence of GDM and POP. CONCLUSION: Three-dimensional perineal ultrasonography of LH size and shape changes can effectively diagnose POP. Age, weight, number of births, number of pregnancies, and weight gain during pregnancy are independent risk factors affecting the cooccurrence of GDM and POP. GDM can increase the LH area in patients, and an enlarged LH leads to an increased incidence of POP.

Sulforaphane suppresses bladder cancer metastasis via blocking actin nucleation-mediated pseudopodia formation.

Metastasis is the primary stumbling block to the treatment of bladder cancer (BC). In order to spread, tumor cells must acquire increased migratory and invasive capacity, which is tightly linked with pseudopodia formation. Here, we unravel the effects of sulforaphane (SFN), an isothiocyanate in cruciferous vegetables, on the assembly of pseudopodia and BC metastasis, and its molecular mechanism in the process. Our database analysis revealed that in bladder tumor, pseudopodia-associated genes, CTTN, WASL and ACTR2/ARP2 are upregulated. SFN caused lamellipodia to collapse in BC cells by blocking the CTTN-ARP2 axis. SFN inhibited invadopodia formation and cell invasion by reducing WASL in different invasive BC cell lines. The production of ATP, essential for the assembly of pseudopodia, was significantly increased in bladder tumors and strongly inhibited by SFN. Overexpressing AKT1 reversed the downregulation of ATP in SFN-treated bladder cancer cells and restored filopodia and lamellipodia morphology and function. Bioluminescent imaging showed that SFN suppressed BC metastases to the lung of nude mice while downregulating Cttn and Arp2 expression. Our study thus reveals mechanisms of SFN action in inhibiting pseudopodia formation and highlights potential targeting options for the therapy of metastatic bladder cancer.

Risk factors for sternal wound infection after median sternotomy: A nested case-control study and time-to-event analysis.

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.

[Profiles of Antibiotic Resistance Genes in the Coastal Aquatic Environment of Xiamen City].

The coastal areas and the adjacent islands are the hotspots of human economic and social activities, including urbanization, industrialization, and agricultural practices, which have profound impacts on the ecological environment of the coastal environment. Antibiotic resistance genes （ARGs）, as emerging contaminants, have become hot topics in water ecological security and public concern. However, the profiles of antibiotic resistome in the costal water remain largely unknown, impeding resistome risk assessment associated with coastal environments. In this study, the high-throughput quantitative PCR technique was used to investigate the abundance and distribution of ARGs in the coastal environment of Xiamen City. Combined with the 16S rDNA gene amplicon sequencing method, the structure and composition of the microbial community in a water environment were investigated, and the influencing factors and associated mechanism of ARGs in seawater were deeply explained. The results of this study showed that a total of 187 ARGs were detected in the coastal water environment, and the abundance level was up to 1.29×1010 copies·L-1. Multidrug resistance, aminoglycosides, and ß lactamase resistance genes were the three main classes of antibiotic resistance genes in the water environment of the Xiamen coastal zone. On the whole, the profile of ARGs was of high abundance, great diversity, and common co-existence, and the coastal water environment was an important hot area and reservoir for antibiotic resistance genes. Twenty-two microbes, including Nautella, Candidatus, Tenacibaculum, Rubripirellula, and Woeseia, were potential carriers of the corresponding 16 antibiotic resistance genes. The mobile genetic elements （MGEs） and microbial community structure accounted for 93.9% of the variation in environmental resistance genes in water. Therefore, microbial community and its mobile genetic elements were the most important driving forces for the occurrence and evolution of ARGs in coastal waters. Based on the results, it is implied that the environmental antibiotic resistance genes in the waters near Xiamen Island have potential risks to water ecological security and human health and highlight the necessity for comprehensive surveillance of ARGs associated with microbial contamination in the coastal aquatic environment.

Wearable and Multiplexed Biosensors based on Oxide Field-Effect Transistors.

Wearable sensors designed for continuous, non-invasive monitoring of physicochemical signals are important for portable healthcare. Oxide field-effect transistor (FET)-type biosensors provide high sensitivity and scalability. However, they face challenges in mechanical flexibility, multiplexed sensing of different modules, and the absence of integrated on-site signal processing and wireless transmission functionalities for wearable sensing. In this work, a fully integrated wearable oxide FET-based biosensor array is developed to facilitate the multiplexed and simultaneous measurement of ion concentrations (H+, Na+, K+) and temperature. The FET-sensor array is achieved by utilizing a solution-processed ultrathin (≈6 nm thick) In2O3 active channel layer, exhibiting high compatibility with standard semiconductor technology, good mechanical flexibility, high uniformity, and low operational voltage of 0.005 V. This work provides an effective method to enable oxide FET-based biosensors for the fusion of multiplexed physicochemical information and wearable health monitoring applications.

Bioengineered mesenchymal stem cell-derived exosomes: emerging strategies for diabetic wound healing.

Diabetic wounds are among the most common complications of diabetes mellitus and their healing process can be delayed due to persistent inflammatory reactions, bacterial infections, damaged vascularization and impaired cell proliferation, which casts a blight on patients'health and quality of life. Therefore, new strategies to accelerate diabetic wound healing are being positively explored. Exosomes derived from mesenchymal stem cells (MSC-Exos) can inherit the therapeutic and reparative abilities of stem cells and play a crucial role in diabetic wound healing. However, poor targeting, low concentrations of therapeutic molecules, easy removal from wounds and limited yield of MSC-Exos are challenging for clinical applications. Bioengineering techniques have recently gained attention for their ability to enhance the efficacy and yield of MSC-Exos. In this review, we summarise the role of MSC-Exos in diabetic wound healing and focus on three bioengineering strategies, namely, parental MSC-Exos engineering, direct MSC-Exos engineering and MSC-Exos combined with biomaterials. Furthermore, the application of bioengineered MSC-Exos in diabetic wound healing is reviewed. Finally, we discuss the future prospects of bioengineered MSC-Exos, providing new insights into the exploration of therapeutic strategies.

Multicenter Validation of lncRNA and Target mRNA Diagnostic and Prognostic Biomarkers of Acute Ischemic Stroke From Peripheral Blood Leukocytes.

BACKGROUND: Long noncoding RNA (lncRNA) and mRNA profiles in leukocytes have shown potential as biomarkers for acute ischemic stroke (AIS). This study aimed to identify altered lncRNA and target mRNA profiles in peripheral blood leukocytes as biomarkers and to assess the diagnostic value and association with AIS prognosis. METHODS AND RESULTS: Differentially expressed lncRNAs (DElncRNAs) and differentially expressed target mRNAs (DEmRNAs) were screened by RNA sequencing in the discovery set, which consisted of 10 patients with AIS and 20 controls. Validation sets consisted of a multicenter (311 AIS versus 303 controls) and a nested case-control study (351 AIS versus 352 controls). The discriminative value of DElncRNAs and DEmRNAs added to the traditional risk factors was estimated with the area under the curve. NAMPT-AS, FARP1-AS1, FTH1, and NAMPT were identified in the multicenter case-control study (P<0.05). LncRNA NAMPT-AS was associated with cis-target mRNA NAMPT and trans-target mRNA FTH1 in all validation sets (P<0.001). Similarly, AIS cases exhibited upregulated lncRNA FARP-AS1 and FTH1 expression (P<0.001) in the nested case-control study (P<0.001). Furthermore, lncRNA FARP1-AS1 expression was upregulated in AIS patients at discharge with an unfavorable outcome (P<0.001). Positive correlations were found between NAMPT expression level and NIHSS scores of AIS patients (P<0.05). Adding 2 lncRNAs and 2 target mRNAs to the traditional risk factor model improved area under the curve by 22.8% and 5.2% in the multicenter and the nested case-control studies, respectively. CONCLUSIONS: lncRNA NAMPT-AS and FARP1-AS1 have potential as diagnostic biomarkers for AIS and exhibit good performance when combined with target mRNA NAMPT and FTH1.

Identification of 6-Fluorine-Substituted Coumarin Analogues as POLRMT Inhibitors with High Potency and Safety for Treatment of Pancreatic Cancer.

Increasing evidence has demonstrated that oxidative phosphorylation (OXPHOS) is closely associated with the progression of pancreatic cancer (PC). Given its central role in mitochondrial transcription, the human mitochondrial RNA polymerase (POLRMT) is a promising target for developing PC treatments. Herein, structure-activity relationship exploration led to the identification of compound S7, which was the first reported POLRMT inhibitor possessing single-digit nanomolar potency of inhibiting PC cells proliferation. Mechanistic studies showed that compound S7 exerted antiproliferative effects without affecting the cell cycle, apoptosis, mitochondrial membrane potential (MMP), or intracellular reactive oxygen species (ROS) levels specifically in MIA PaCa-2 cells. Notably, compound S7 inhibited tumor growth in MIA PaCa-2 xenograft tumor model with a tumor growth inhibition (TGI) rate of 64.52% demonstrating significant improvement compared to the positive control (44.80%). In conclusion, this work enriched SARs of POLRMT inhibitors, and compound S7 deserved further investigations of drug-likeness as a candidate for PC treatment.

Electrocatalytic coupled biofilter for treating cyclohexanone-containing wastewater: Degradation, mechanism and optimization.

Electrocatalytic coupled biofilter (EBF) technology organically integrates the characteristics of electrochemistry and microbial redox, providing ideas for effectively improving biological treatment performance. In this study, an EBF system was developed for enhanced degradation of cyclohexanone in contaminated water. Experimental results show that the system can effectively remove cyclohexanone in contaminated water. Under the optimal parameters, the removal rates of cyclohexanone, TP, NH4+-N and TN were 97.61 ± 1.31%, 76.31 ± 1.67%, 94.14 ± 2.13% and 95.87 ± 1.01% respectively. Degradation kinetics studies found that electrolysis, adsorption, and biodegradation pathways play a major role in the degradation of cyclohexanone. Microbial community analysis indicates that voltage can affect the structure of the microbial community, with the dominant genera shifting from Acidovorax (0 V) to Brevundimonas (0.7 V). Additionally, Acidovorax, Cupriavidus, Ralstonia, and Hydrogenophaga have high abundance in the biofilm and can effectively metabolize cyclohexanone and its intermediates, facilitating the removal of cyclohexanone. In summary, this research can guide the development and construction of highly stable EBF systems and is expected to be used for advanced treatment of industrial wastewater containing cyclohexanone.

Research status and hotspots of social frailty in older adults: a bibliometric analysis from 2003 to 2022.

Background: Social Frailty is a significant public health concern affecting the elderly, particularly with the global population aging rapidly. Older adults with social frailty are at significantly higher risk of adverse outcomes such as disability, cognitive impairment, depression, and even death. In recent years, there have been more and more studies on social frailty, but no bibliometrics has been used to analyze and understand the general situation in this field. Therefore, by using CiteSpace, VOSviewer, and Bilioshiny software programs, this study aims to analyze the general situation of the research on social frailties of the older adults and determine the research trends and hot spots. Methods: A bibliometric analysis was conducted by searching relevant literature on the social frailty of the older adults from 2003 to 2022 in the Web of Science core database, using visualization software to map publication volume, country and author cooperation networks, keyword co-occurrences, and word emergence. Results: We analyzed 415 articles from 2003 to 2022. Brazil has the highest number of articles in the field of social frailty of the older adults, and the United States has the highest number of cooperative publications. Andrew MK, from Canada, is the most published and co-cited author, with primary research interests in geriatric assessment, epidemiology, and public health. "Social Vulnerability," "Health," "Frailty," "Mortality," and "Older Adult" are among the research hotspots in this field. "Dementia," "Alzheimer's disease," "Population," and "Covid-19" are emerging research trends in social frailty among the older adults. Conclusion: This scientometric study maps the research hotspots and trends for the past 20 years in social frailty among the older adults. Our findings will enable researchers to better understand trends in this field and find suitable directions and partners for future research.