Prostate Health Index density aids the diagnosis of prostate cancer detected using magnetic resonance imaging targeted prostate biopsy in Taiwanese multicenter study.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted prostate biopsy is the current standard for diagnosing prostate cancer (PCa). However, studies evaluating the value of biomarkers, including prostate health index (PHI) and its derivatives using this method are limited. We aimed to investigate the efficacy of PHI density (PHID) in guiding MRI-targeted prostate biopsies to identify clinically significant prostate cancers (csPCa). METHODS: The multicenter prospectively registered prostate biopsy database from three medical centers in Taiwan included patients with PHI and MRI targeted and/or systematic prostate biopsies. We assessed the required values of prostate-specific antigen (PSA), prostate volume, PHI, PHID, and Prostate Imaging Reporting & Data System (PI-RADS) score using multivariable analyses, receiver operating characteristic curve analysis, and decision curve analyses (DCA). csPCa was defined as the International Society of Urological Pathology Gleason group ≥2 PCa, with an emphasis on reducing unwarranted biopsies. RESULTS: The study cohort comprised 420 individuals. Diagnoses of PCa and csPCa were confirmed in 62.4% and 47.9% of the participants, respectively. The csPCa diagnosis rates were increased with increasing PI-RADS scores (20.5%, 44.2%, and 73.1% for scores 3, 4, and 5, respectively). Independent predictors for csPCa detection included PHI, prostate volume, and PI-RADS scores of 4 and 5 in multivariable analyses. The area under the curve (AUC) for csPCa of PHID (0.815) or PHI (0.788) was superior to that of PSA density (0.746) and PSA (0.635) in the entire cohort, and the superiority of PHID (0.758) was observed in PI-RADS 3 lesions. DCA revealed that PHID achieved the best net clinical benefit in PI-RADS 3-5 and 4/5 cases. Among PI-RADS 3 lesions, cutoff values of PHID 0.70 and 0.43 could eliminate 51.8% and 30.4% of omitted biopsies, respectively. CONCLUSION: PHI-derived biomarkers, including PHID, performed better than other PSA-derived biomarkers in diagnosing PCa in MRI detected lesions.

Integration of Lipidomics and Transcriptomics Identifies the Regulation of Lipid Homeostasis as Potential Mechanisms of Konjac Glucomannan against Hepatic Steatosis.

Hepatic steatosis is characterized by substantial disruption in the liver's lipid level regulation. Konjac glucomannan (KGM) is acknowledged as a nutritious food that has the potential to prevent hyperlipidemia. This study utilized lipidomics and transcriptomics to investigate the efficacy of KGM in alleviating high-fat diet-induced hepatic steatosis by regulating lipid homeostasis. The findings indicated that supplementation of KGM for a duration of 10 weeks led to significant decreases in body weight, liver weight, and epididymal fat tissue weight. Furthermore, improvements in lipid concentrations in plasma and liver samples were observed, along with enhancements in glucose tolerance and the mitigation of liver damage. Additionally, lipidomics analysis revealed that the primary differential lipid metabolites were mainly associated with fatty acid metabolism pathways. Transcriptomic analysis showed that KGM significantly altered the gene expression of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the liver. Moreover, KGM demonstrated a significant regulatory impact on the hepatic expression of PPARγ, potentially mitigating hepatic steatosis through modulation of the PPARγ-mediated lipid metabolism pathway. In conclusion, these findings suggest that KGM effectively mitigates steatosis by modulating hepatic lipid metabolites and controlling PPARγ-mediated genes in the liver.

Influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. RESULTS: Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 µg·mL-1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) (p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2, CYP2C19*3, CYP2C19*17, and UGT1A4 (rs2011425) (p > 0.05). CONCLUSION: There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.

Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r  = 0.17; P  < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ±â€…297.1 vs. 633.8 ±â€…305.5 µg/ml; P  = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ±â€…1.7 vs. 3.8 ±â€…2.0; P  = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ±â€…293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ±â€…165.6 ng/ml and 260.0 ±â€…36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ±â€…285.6 vs. 433.0 ±â€…227.2 ng/ml; P  = 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

CHD2 Regulates Neuron-glioma Interactions in Pediatric Glioma.

High-grade gliomas (HGG) are deadly diseases for both adult and pediatric patients. Recently, it has been shown that neuronal activity promotes progression of multiple subgroups of HGG. However, epigenetic mechanisms that govern this process remain elusive. Here we report that the chromatin remodeler CHD2 regulates neuron-glioma interactions in diffuse midline glioma (DMG) characterized by onco-histone H3.1K27M. Depletion of CHD2 in H3.1K27M DMG cells compromises cell viability and neuron-to-glioma synaptic connections in vitro, neuron-induced proliferation of H3.1K27M DMG cells in vitro and in vivo, activity-dependent calcium transients in vivo, and extends the survival of H3.1K27M DMG-bearing mice. Mechanistically, CHD2 coordinates with the transcription factor FOSL1 to control the expression of axon-guidance and synaptic genes in H3.1K27M DMG cells. Together, our study reveals a mechanism whereby CHD2 controls the intrinsic gene program of the H3.1K27M DMG subtype, which in turn regulates the tumor growth-promoting interactions of glioma cells with neurons.

Alteration Trend and Overlap Analysis of Positive Features in Different-Sized Benign and Malignant Thyroid Nodules: Based on Chinese Thyroid Imaging Reporting and Data System.

Purpose: This study aimed to investigate the alteration trends and overlaps of positive features in benign and malignant thyroid nodules of different sizes based on the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). Patients and Methods: 1337 patients with 1558 thyroid nodules were retrospectively recruited from November 2021 to December 2023. These nodules were divided into three groups according to maximum diameter: A (≤10 mm), B (10-20 mm), and C (≥20 mm). C-TIRADS positive features were compared between benign and malignant thyroid nodules of different sizes. In addition, the trends of positive features with changes in nodule size among malignant thyroid nodules were analyzed. Results: The incidence of positive features in malignant thyroid nodules was higher than that in benign. As benign nodules grow, the incidence of all positive features showed a linear decreasing trend (Z values were 72.103, 101.081, 17.344, 33.909, and 129.304, P values < 0.001). With the size of malignant thyroid nodules increased, vertical orientation, solid, marked hypoechogenicity, and ill-defined/irregular margins/extrathyroidal extension showed a linear decreasing trend (Z = 148.854, 135.378, 8.590, and 69.239, respectively; P values < 0.05), while suspicious microcalcifications showed a linear increasing trend (Z = 34.699, P<0.001). In terms of overlapping characteristics, group A had a significantly higher overlapping rate than the other two groups, and the overlapping rate of solid indicators remained the highest among all three groups (P < 0.05). Conclusion: Differences in positive features were observed between thyroid nodules of different sizes. Except for suspicious microcalcifications, the incidence of other four positive features decreased with increasing nodule size. In addition, a negative correlation was observed between the overlap rate and nodule size. These results may provide a basis for sonographers to upgrade or downgrade thyroid nodules based on their own experience.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.

Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.

A Transformable Specific-Responsive Peptide for One-Step Synergistic Therapy of Bladder Cancer.

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8+ T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer.

Epidemiological Surveillance: Genetic Diversity of Rotavirus Group A in the Pearl River Delta, Guangdong, China in 2019.

Objective: This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China. Methods: This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA. Results: The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains. Conclusion: This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

GINS1 promotes ZEB1-mediated epithelial-mesenchymal transition and tumor metastasis via ß-catenin signaling in hepatocellular carcinoma.

GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through ß-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via ß-catenin signaling in HCC.

Focused ultrasound-mediated blood-brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma.

BACKGROUND: Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood-brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. METHODS: To establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53-/-). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI). RESULTS: FUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3-4 weeks post-RT. CONCLUSION: Repeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.

Performance of metagenomic next-generation sequencing in cerebrospinal fluid for diagnosis of tuberculous meningitis.

Purpose. Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases, while its performance in diagnosis of tuberculous meningitis (TBM) is incompletely characterized. The aim of this study was to assess the performance of mNGS in the diagnosis of TBM, and illustrate the sensitivity and specificity of different methods.Methods. We retrospectively recruited TBM patients between January 2021 and March 2023 to evaluate the performance of mNGS on cerebrospinal fluid (CSF) samples, in comparison with conventional microbiological testing, including culturing of Mycobacterium tuberculosis (MTB), acid-fast bacillus (AFB) stain, reverse transcription PCR and Xpert MTB/RIF.Results. Of the 40 enrolled, 34 participants were diagnosed with TBM, including 15(44.12 %) definite and 19(55.88 %) clinical diagnosis based upon clinical manifestations, CSF parameters, brain imaging, pathogen evidence and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MTBC) in 11 CSF samples. In patients with definite TBM, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mNGS were 78.57, 100, 100, 66.67 and 85 %, respectively. Compared to conventional diagnostic methods, the sensitivity of mNGS (78.57 %) was higher than AFB (0 %), culturing (0 %), RT-PCR (60 %) and Xpert MTB/RIF (14.29 %).Conclusions. Our study indicates that mNGS of CSF exhibited an overall improved sensitivity over conventional diagnostic methods for TBM and can be considered a front-line CSF test.

New Analogues of Amides and Quinolinones Produced by Streptomyces sp. YIM S01983.

Streptomide (1), a new amide analogue, streptomynone (2), a new quinolinone, and ten known compounds including three aliphatic acids (3-5), two amides (6-7), four cyclic dipeptides (8-11), and an adenosine (12) were isolated from the fermentation broth of Streptomyces sp. YIM S01983 isolated from a sediment sample collected in Bendong Village, Huadong Town, Chuxiong, China. Their structures were determined by analysis of the 1D/2D-NMR and HR-ESI-MS spectra. Compound 12 presented weak antimicrobial activities against Candida albicans and Aligenes faecalis (MIC=64 µg/mL). Compounds 7 and 12 showed weak cytotoxic activity against MHCC97H.

Silkworm pupae protein co-degradation by magnetic nanoparticles immobilized proteinase K and Mucor circinelloides aspartic protease for further utilization of sericulture by-products.

Silkworm pupae, by-product of sericulture industry, is massively discarded. The degradation rate of silkworm pupae protein is critical to further employment, which reduces the impact of waste on the environment. Herein, magnetic Janus mesoporous silica nanoparticles immobilized proteinase K mutant T206M and Mucor circinelloides aspartic protease were employed in the co-degradation. The thermostability of T206M improved by enhancing structural rigidity (t1/2 by 30 min and T50 by 5 °C), prompting the degradation efficiency. At 65 °C and pH 7, degradation rate reached the highest of 61.7%, which improved by 26% compared with single free protease degradation. Besides, the immobilized protease is easy to separate and reuse, which maintains 50% activity after 10 recycles. Therefore, immobilized protease co-degradation was first applied to the development and utilization of silkworm pupae resulting in the release of promising antioxidant properties and reduces the environmental impact by utilizing a natural and renewable resource.

Immune Response following FLASH and Conventional Radiation in Diffuse Midline Glioma.

PURPOSE: Diffuse midline glioma (DMG) is a fatal tumor traditionally treated with radiation therapy (RT) and previously characterized as having a noninflammatory tumor immune microenvironment (TIME). FLASH is a novel RT technique using ultra-high dose rate that is associated with decreased toxicity and effective tumor control. However, the effect of FLASH and conventional (CONV) RT on the DMG TIME has not yet been explored. METHODS AND MATERIALS: Here, we performed single-cell RNA sequencing (scRNA-seq) and flow cytometry on immune cells isolated from an orthotopic syngeneic murine model of brainstem DMG after the use of FLASH (90 Gy/sec) or CONV (2 Gy/min) dose-rate RT and compared to unirradiated tumor (SHAM). RESULTS: At day 4 post-RT, FLASH exerted similar effects as CONV in the predominant microglial (MG) population, including the presence of two activated subtypes. However, at day 10 post-RT, we observed a significant increase in the type 1 interferon α/ß receptor (IFNAR+) in MG in CONV and SHAM compared to FLASH. In the non-resident myeloid clusters of macrophages (MACs) and dendritic cells (DCs), we found increased type 1 interferon (IFN1) pathway enrichment for CONV compared to FLASH and SHAM by scRNA-seq. We observed this trend by flow cytometry at day 4 post-RT in IFNAR+ MACs and DCs, which equalized by day 10 post-RT. DMG control and murine survival were equivalent between RT dose rates. CONCLUSIONS: Our work is the first to map CONV and FLASH immune alterations of the DMG TIME with single-cell resolution. Although DMG tumor control and survival were similar between CONV and FLASH, we found that changes in immune compartments differed over time. Importantly, although both RT modalities increased IFN1, we found that the timing of this response was cell-type and dose-rate dependent. These temporal differences, particularly in the context of tumor control, warrant further study.

Asynchronous propagation of atomic force and excited electronic charge in GaAs under proton irradiation.

The studies for the interaction of energetic particles with matter have greatly contributed to the exploration of material properties under irradiation conditions, such as nuclear safety, medical physics and aerospace applications. In this work, we theoretically simulate the non-adiabatic process for GaAs upon proton irradiation using time-dependent density functional theory, and find that the radial propagation of force on atoms and the excitation of electron in GaAs are non-synchronous process. We calculated the electronic stopping power on proton with the velocity of 0.1-0.6 a.u., agreement with the previous empirical results. After further analyzing the force on atoms and the population of excited electrons, we find that under proton irradiation, the electrons around the host atoms at different distances from the proton trajectories are excited almost simultaneously, especially those regions with relatively high charge density. However, the distant atoms have a significant hysteresis in force, which occurs after the surrounding electrons are excited. In addition, hysteresis in force and electron excitation behavior at different positions are closely related to the velocity of proton. This non-synchronous propagation reveals the microscopic dynamic mechanism of energy deposition into the target material under ion irradiation.

Mid-Term Diabetes Remission Outcome in Patients with BMI ≤ 30 kg/m2 Following Sleeve Gastrectomy.

BACKGROUND: Bariatric and metabolic surgery is recommended for Asian patients with type 2 diabetes mellitus (T2DM) and BMI ≥ 27.5 kg/m2. However, mid to long-term ·evidence is still lacking. METHODS: Patients' data that underwent laparoscopic sleeve gastrectomy (SG) as the primary surgery at the Affiliated Hospital of Xuzhou Medical University were analyzed. Patients with T2DM diagnosed with either fasting blood glucose (FBG) ≥ 7.0 mmol/L or glycosylated hemoglobin (HbA1c) level ≥ 7.0% and 27.5 ≤ BMI ≤ 30 kg/m2 were included. RESULTS: 24 patients (7 male and 17 female) were included in this study. With a mean follow-up duration of 4.5 ± 1.1 years, the mean percentage of total weight loss (%TWL) was 14.4 ± 6.7%. Postoperatively, nine patients (37%) still required oral anti-diabetic medications, while no patients used insulin. FBG and HbA1c levels declined to 6.3 ± 1.5 mmol/L and 6.0 ± 1.0%, respectively. Fifteen patients (63%) were with HbA1c levels < 7% and without medication requirements, five patients (21%) were with HbA1c levels < 7% with the help of oral anti-diabetic medication, and four patients (16%) were with HbA1c levels > 7% with the help of oral anti-diabetic medication. CONCLUSIONS: Our study provides further evidence that SG could result in both T2DM improvement and remission in patients with BMI ≤ 30 kg/m2. Longer follow-up duration and larger sample will be needed in the future.

Microbiota in adult perianal abscess revealed by metagenomic next-generation sequencing.

The microbiota of perianal abscesses is scarcely investigated. Identifying causative bacteria is essential to develop antibiotic therapy. However, culture-based methods and molecular diagnostics through 16S PCR technology are often hampered by the polymicrobial nature of perianal abscesses. We sought to characterize the microbiota composition of perianal abscesses via metagenomic next-generation sequencing (mNGS). Fourteen patients suffering from perianal abscesses between March 2023 and August 2023 underwent retrospective assessment. Information from medical records was used, including clinical information, laboratory data, and culture and mNGS results. Forty bacterial taxa were identified from perianal abscesses through mNGS, with Bilophila wadsworthia (71.4%), Bacteroides fragilis (57.1%), and Escherichia coli (50.0%) representing the most prevalent species. mNGS identified an increased number of bacterial taxa, with an average of 6.1 compared to a traditional culture-based method which only detected an average of 1.1 in culture-positive perianal abscess patients, predominantly E. coli (75.0%), revealing the polymicrobial nature of perianal abscesses. Our study demonstrates that a more diverse bacterial profile is detected by mNGS in perianal abscesses, and that Bilophila wadsworthia is the most prevalent microorganism, potentially serving as a potential biomarker for perianal abscess.IMPORTANCEAccurately, identifying the bacteria causing perianal abscesses is crucial for effective antibiotic therapy. However, traditional culture-based methods and 16S PCR technology often struggle with the polymicrobial nature of these abscesses. This study employed metagenomic next-generation sequencing (mNGS) to comprehensively analyze the microbiota composition. Results revealed 40 bacterial taxa, with Bilophila wadsworthia (71.4%), Bacteroides fragilis (57.1%), and Escherichia coli (50.0%) being the most prevalent species. Compared to the culture-based approach, mNGS detected a significantly higher number of bacterial taxa (average 6.1 vs 1.1), highlighting the complex nature of perianal abscesses. Notably, Bilophila wadsworthia emerged as a potential biomarker for these abscesses. This research emphasizes the importance of mNGS in understanding perianal abscesses and suggests its potential for improving diagnostic accuracy and guiding targeted antibiotic therapy in the future.

Improvement of an enzymatic cascade synthesis of nicotinamide mononucleotide via protein engineering and reaction-process reinforcement.

Enzymatic synthesis of ß-nicotinamide mononucleotide (NMN) from D-ribose has garnered widespread attention due to its cheap material, the use of mild reaction conditions, and the ability to produce highly pure products with the desired optical properties. However, the overall NMN yield of this method is impeded by the low activity of rate-limiting enzymes. The ribose-phosphate diphosphokinase (PRS) and nicotinamide phosphoribosyltransferase (NAMPT), that control the rate of the reaction, were engineered to improve the reaction efficacy. The actives of mutants PRS-H150Q and NAMPT-Y15S were 334% and 57% higher than that of their corresponding wild-type enzymes, respectively. Furthermore, by adding pyrophosphatase, the byproduct pyrophosphate which can inhibit the activity of NAMPT was degraded, leading to a 6.72% increase in NMN yield. Following with reaction-process reinforcement, a high yield of 8.10 g L-1 NMN was obtained after 3 h of reaction, which was 56.86-fold higher than that of the stepwise reaction synthesis (0.14 g L-1 ), indicating that the in vitro enzymatic synthesis of NMN from D-ribose and niacinamide is an economical and feasible route.