Chitinophaga pollutisoli sp. nov., isolated from contaminated sediment.

A Gram-stain-negative, yellow-pigmented, and facultatively aerobic bacterium, designated strain GPA1T, was isolated from plastic waste landfill soil in the Republic of Korea. The cells were non-motile short rods exhibiting oxidase-negative and catalase-positive activities. Growth was observed at 15-40 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 7.0-8.0) and in the presence of 0-2.5 % (w/v) NaCl (optimum, 0 %). Menaquinone-7 was the sole respiratory quinone, and iso-C15 : 0, C16 : 1 ω5c, and iso-C17 : 0 3-OH were the major cellular fatty acids (>10 % of the total fatty acids). Phosphatidylethanolamine was identified as a major polar lipid. Phylogenetic analyses based on 16S rRNA gene sequences and 120 concatenated marker protein sequences revealed that strain GPA1T formed a distinct lineage within the genus Chitinophaga. The genome of strain GPA1T was 6078 kb in size with 53.8 mol% G+C content. Strain GPA1T exhibited the highest similarity to Chitinophaga rhizosphaerae T16R-86T, with a 98.6 % 16S rRNA gene sequence similarity, but their average nucleotide identity and digital DNA-DNA hybridization values were 82.5 and 25.9 %, respectively. Based on its phenotypic, chemotaxonomic, and phylogenetic characteristics, strain GPA1T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga pollutisoli sp. nov. is proposed. The type strain is GPA1T (=KACC 23415T=JCM 36644T).

The Relationship between High-Intensity Physical Activity and Traumatic Dental Injury among Young Adults in South Korea.

Materials and Methods: This study analyzed data collected from the 5th National Health and Nutrition Examination Survey (KNHANES V:2010-2012). The total number of participants in the 5th KNAHANES was 5,383 young adults aged 19-39 years, selected from 25,534 participants. Logistic regression analysis was performed using socioeconomic status (sex, age, education level, and income), physical activity intensity (vigorous and moderate), frequency of vigorous and moderate physical activity (days per week), and traumatic dental injuries due to exercise. Results: A total of 5,383 participants were included in the analysis. High-intensity exercisers had a statistically different association with traumatic dental injuries due to exercise. In all models, high-intensity exercisers had more traumatic dental injuries than moderate-intensity exercisers, and participants who exercised vigorously 4 or more days per week had a significantly higher prevalence experience of traumatic dental injuries. Among adults in their 20s, men, college attendees, and those with higher incomes, the prevalence of exercising vigorously 4 or more days per week was higher. Conclusions: Among young adults, a higher frequency of high-intensity physical activity was associated with a higher prevalence experience of traumatic tooth injury due to exercise compared with no physical activity.

Isoxerophilusins A and B, Two Novel Polycyclic Asymmetric Diterpene Dimers from Isodon xerophilus: Structural Elucidation, Modification, and Inhibitory Activities against α-Glucosidase.

Isoxerophilusins A (1) and B (2), two unprecedented diterpene heterodimers biogenetically from ent-atisanes and abietanes, were isolated from the rhizomes of Isodon xerophilus. Their structures were determined by extensive spectroscopic analysis and single-crystal X-ray diffraction. Selective esterification of 1 generated 11 new derivatives. All derivatives showed excellent α-glucosidase inhibitory activity in comparison to acarbose. Compounds 12 and 13 demonstrated significant inhibition against α-glucosidase with IC50 values of 4.92 and 3.83 µM, respectively.

Anatomical assessments of injectate spread stratified by the volume of the intertransverse process block at the T2 level.

BACKGROUND: This cadaveric study aimed to analyze injectate spread to target nerves during a single-injection, ultrasound-guided intertransverse process block. METHODS: An ultrasound-guided intertransverse process block with three different injectate volumes was administered to 12 cadavers. Each hemithorax was subjected to computer-generated random allocation of 10, 15, or 20 mL ultrasound-guided, single-injection intertransverse process block at the T2 vertebral level. Latex dye solution was injected into each hemithorax in accordance with the allocated volume. The presence of dye at the nerve root in the sympathetic chain and intercostal nerves at various injection levels was examined via dissection. RESULTS: Injectate spread into the dorsal rami was observed in seven of eight (87.5%), seven of eight (87.5%), and all eight (100%) of the 10, 15, and 20 mL specimens, respectively. In all 20 mL specimens, consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion was observed. CONCLUSIONS: An injectate volume of 20 mL was required for consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion in an intertransverse process block. Although an augmented injectate volume was associated with an increased likelihood of target nerve staining, consistent staining of the sympathetic ganglion, rami communicans, and ventral ramus was not observed, even at a volume of 20 mL. The current study presents initial findings suggesting that as opposed to a sympathetic ganglion block, a 20 mL intertransverse process block may act as a feasible substitute for dorsal root ganglion, spinal nerve, and medial branch blocks within a clinical context.

A causal link between circulating leukocytes and three major urologic cancers: a mendelian randomization investigation.

Purpose: This study aimed to explore the influence of serum leukocytes on urologic cancers (UC) using observation-based investigations. In the present study, Mendelian randomization (MR) was employed to assess the link between leukocyte count (LC) and the risk of UC development. Methods: Five LC and three major UC patient prognoses were obtained for MR analysis from genome-wide association studies (GWAS). Furthermore, in order to evaluate reverse causality, bidirectional studies were conducted. Finally, a sensitivity analysis using multiple methods was carried out. Results: There was no significant correlation found in the genetic assessment of differential LC between the co-occurrence of bladder cancer (BCA) and renal cell carcinoma (RCC). Conversely, an individual 1-standard deviation (SD) rise in neutrophil count was strongly linked to a 9.3% elevation in prostate cancer (PCA) risk ([odd ratio]OR = 1.093, 95% [confidence interval]CI = 0.864-1.383, p = 0.002). Reverse MR analysis suggested that PCA was unlikely to cause changes in neutrophil count. Additional sensitivity studies revealed that the outcomes of all MR evaluations were similar, and there was no horizontal pleiotropy. Primary MR analysis using inverse-variance weighted (IVW) revealed that differential lymphocyte count significantly influenced RCC risk (OR = 1.162, 95%CI = 0.918-1.470, p = 0.001). Moreover, altered basophil count also affected BCA risk (OR = 1.249, 95% CI = 0.904-1.725, p = 0.018). Nonetheless, these causal associations were not significant in the sensitivity analysis. Conclusion: In summary, the results revealed that increased neutrophil counts represent a significant PCA risk factor. The current research indicates a significant relationship between immune cell activity and the cause of UC.

Hsp47 promotes biogenesis of multi-subunit neuroreceptors in the endoplasmic reticulum.

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABAA) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABAA receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5) and preferentially binds the folded conformation of GABAA receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABAA receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABAA receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.

Perioperative liberal drinking management promotes postoperative gastrointestinal function recovery after gynecological laparoscopic surgery: A randomized controlled trial.

STUDY OBJECTIVE: This study aims to evaluate the effect of perioperative liberal drinking management, including preoperative carbohydrate loading (PCL) given 2 h before surgery and early oral feeding (EOF) at 6 h postoperatively, in enhancing postoperative gastrointestinal function and improving outcomes in gynecologic patients. The hypotheses are that the perioperative liberal drinking management accelerates the recovery of gastrointestinal function, enhances dietary tolerance throughout hospitalization, and ultimately reduces the length of hospitalization. DESIGN: A prospective randomized controlled trial. SETTING: Operating room and gynecological ward in Wuhan Union Hospital. PATIENTS: We enrolled 210 patients undergoing elective gynecological laparoscopic surgery, and 157 patients were included in the final analysis. INTERVENTIONS: Patients were randomly allocated in a 1:1:1 ratio into three groups, including the control, PCL, and PCL-EOF groups. The anesthetists and follow-up staff were blinded to group assignment. MEASUREMENTS: The primary outcome was the postoperative Intake, Feeling nauseated, Emesis, Examination, and Duration of symptoms (I-FEED) score (range 0 to 14, higher scores worse). Secondary outcomes included the incidence of I-FEED scores >2, and other additional indicators to monitor postoperative gastrointestinal function, including time to first flatus, time to first defecation, time to feces Bristol grade 3-4, and time to tolerate diet. Additionally, we collected other ERAS recovery indicators, including the incidence of PONV, complications, postoperative pain score, satisfaction score, and the quality of postoperative functional recovery at discharge. MAIN RESULTS: The PCL-EOF exhibited significantly enhanced gastrointestinal function recovery compared to control group and PCL group (p < 0.05), with the lower I-FEED score (PCL: 0[0,1] vs. PCL-EOF: 0[0,0] vs. control: 1[0,2]) and the reduced incidence of I-FEED >2 (PCL:8% vs. PCL-EOF: 2% vs. control:21%). Compared to the control, the intervention of PCL-EOF protected patients from the incidence of I-FEED score > 2 [HR:0.09, 95%CI (0.01-0.72), p = 0.023], and was beneficial in promoting the patient's postoperative first flatus [PCL-EOF: HR:3.33, 95%CI (2.14-5.19),p < 0.001], first defecation [PCL-EOF: HR:2.76, 95%CI (1.83-4.16), p < 0.001], Bristol feces grade 3-4 [PCL-EOF: HR:3.65, 95%CI (2.36-5.63), p < 0.001], first fluid diet[PCL-EOF: HR:2.76, 95%CI (1.83-4.16), p < 0.001], and first normal diet[PCL-EOF: HR:6.63, 95%CI (4.18-10.50), p < 0.001]. Also, the length of postoperative hospital stay (PCL-EOF: 5d vs. PCL: 6d and control: 6d, p < 0.001), the total cost (PCL-EOF: 25052 ± 3650y vs. PCL: 27914 ± 4684y and control: 26799 ± 4775y, p = 0.005), and postoperative VAS pain score values [POD0 (PCL-EOF: 2 vs. control: 4 vs. PCL: 4, p < 0.001), POD1 (PCL-EOF: 1 vs. control: 3 vs. PCL: 2, p < 0.001), POD2 (PCL-EOF: 1 vs. control:2 vs. PCL: 1, p < 0.001), POD3 (PCL-EOF: 0 vs. control: 1 vs. PCL: 1, p < 0.001)] were significantly reduced in PCL-EOF group. CONCLUSIONS: Our primary endpoint, I-FEED score demonstrated significant reduction with perioperative liberal drinking, serving as a protective intervention against I-FEED>2. Gastrointestinal recovery metrics, such as time to first flatus and defecation, also showed substantial improvements. Furthermore, the intervention enhanced postoperative dietary tolerance and expedited early recovery. TRIAL REGISTRATION: ChiCTR2300071047(https://www.chictr.org.cn/).

Supplementation of Mangiferin to a High-Starch Diet Alleviates Hepatic Injury and Lipid Accumulation Potentially through Modulating Cholesterol Metabolism in Channel Catfish (Ictalurus punctatus).

Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish (Ictalurus punctatus) were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) (p = 0.031), specific growth rate (SGR) (p = 0.039), and feed conversion efficiency (FCE) (p = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group (p = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) (p = 0.000), triglyceride (TG) (p= 0.001), and low-density lipoprotein cholesterol (LDL) (p = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels (p = 0.000) and liver TC levels (p = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (hmgcr, sqle, srebf2, sp1, and ldlr) and increasing the expression of genes that are involved in cholesterol catabolism (cyp7a1). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold (p = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group (p = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of sqle (p = 0.030) and reduced cholesterol levels (p = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle (p = 0.000) and reduced cholesterol levels (p = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture.

A Subset of Microsatellite Unstable Cancer Genomes Prone to Short Insertions over Deletions Is Associated with Elevated Anticancer Immunity.

Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome Atlas and International Cancer Genome Consortium to conduct a comprehensive analysis of MSI-associated cancers, focusing on indel mutational signatures. We classified MSI-high genomes into two subtypes based on their indel profiles: deletion-dominant (MMRd-del) and insertion-dominant (MMRd-ins). Compared with MMRd-del genomes, MMRd-ins genomes exhibit distinct mutational and transcriptomic features, including a higher prevalence of T>C substitutions and related mutation signatures. Short insertions and deletions in MMRd-ins and MMRd-del genomes target different sets of genes, resulting in distinct indel profiles between the two subtypes. In addition, indels in the MMRd-ins genomes are enriched with subclonal alterations that provide clues about a distinct evolutionary relationship between the MMRd-ins and MMRd-del genomes. Notably, the transcriptome analysis indicated that MMRd-ins cancers upregulate immune-related genes, show a high level of immune cell infiltration, and display an elevated neoantigen burden. The genomic and transcriptomic distinctions between the two types of MMRd genomes highlight the heterogeneity of genetic mechanisms and resulting genomic footprints and transcriptomic changes in cancers, which has potential clinical implications.

Recent advances in the application of [2 + 2] cycloaddition in the chemical synthesis of cyclobutane-containing natural products.

Cyclobutanes are distributed widely in a large class of natural products featuring diverse pharmaceutical activities and intricate structural frameworks. The [2 + 2] cycloaddition is unequivocally the primary and most commonly used method for synthesizing cyclobutanes. In this review, we have summarized the application of the [2 + 2] cycloaddition with different reaction mechanisms in the chemical synthesis of selected cyclobutane-containing natural products over the past decade.

Acteoside delays the fibrosis process of diabetic nephropathy by anti-oxidation and regulating the autophagy-lysosome pathway.

Renal fibrosis is the final pathological change of kidney disease, it has also been recognized to be critical for the final progression of diabetic nephropathy (DN) to kidney failure. Acteoside (ACT) is a phenylethanoid glycoside widely distributed in dicotyledonous plants. It has many pharmacological activities, such as anti-oxidation, anti-inflammation, anti-cancer, neuroprotection, cardiovascular protection, anti-diabetes, bone and cartilage protection, liver and kidney protection, and antibacterial activity. This study aims to investigate the protective effects of ACT on renal interstitial fibrosis in rats with DN induced by intraperitoneal injection of streptozocin (STZ) combined with unilateral nephrectomy and its mechanism. In vivo and in vitro, the effects of ACT on reactive oxygen species (ROS) level, oxidative tubular injury, as well as damage of autophagic flux and lysosome in the DN model were detected. Results indicate that administration of ACT delayed the progression of renal interstitial fibrosis in DN by anti-oxidation and regulating the autophagy-lysosome pathway, which may potentially be attributed to the regulatory influence of ACT on transcription factor EB (TFEB).

FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer.

FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the chromatin binding of the androgen receptor (AR) in both normal prostate epithelial cells and the luminal subtype of prostate cancer (PCa). Recent studies have highlighted the emergence of FOXA2 as an adaptive response to AR signaling inhibition treatments. However, the role of the FOXA1 to FOXA2 transition in regulating cancer lineage plasticity remains unclear. Our study demonstrates that FOXA2 binds to distinct classes of developmental enhancers in multiple AR-independent PCa subtypes, with its binding depending on LSD1. Moreover, we reveal that FOXA2 collaborates with JUN at chromatin and promotes transcriptional reprogramming of AP-1 in lineage-plastic cancer cells, thereby facilitating cell state transitions to multiple lineages. Overall, our findings underscore the pivotal role of FOXA2 as a pan-plasticity driver that rewires AP-1 to induce the differential transcriptional reprogramming necessary for cancer cell lineage plasticity.

Optimal minimum MU for intensity-modulated proton therapy with pencil-beam scanning proton beams.

PURPOSE: A higher minimum monitor unit (minMU) for pencil-beam scanning proton beams in intensity-modulated proton therapy is preferred for more efficient delivery. However, plan quality may be compromised when the minMU is too large. This study aimed to identify the optimal minMU (OminMU) to improve plan delivery efficiency while maintaining high plan quality. METHODS: We utilized clinical plans including six anatomic sites (brain, head and neck, breast, lung, abdomen, and prostate) from 23 patients previously treated with the Varian ProBeam system. The minMU of each plan was increased from the current clinical minMU of 1.1 to 3-24 MU depending on the daily prescribed dose (DPD). The dosimetric parameters of the plans were evaluated for consistency against a 1.1-minMU plan for target coverage as well as organs-at-risk dose sparing. DPD/minMU was defined as the ratio of DPD to minMU (cGy/MU) to find the OminMU by ensuring that dosimetric parameters did not differ by >1% compared to those of the 1.1-minMU plan. RESULTS: All plans up to 5 minMU showed no significant dose differences compared to the 1.1-minMU plan. Plan qualities remained acceptable when DPD/minMU ≥35 cGy/MU. This suggests that the 35 cGy/MU criterion can be used as the OminMU, which implies that 5 MU is the OminMU for a conventional fraction dose of 180 cGy. Treatment times were decreased by an average of 32% (max 56%, min 7%) and by an average of 1.6 min when the minMU was increased from 1.1 to OminMU. CONCLUSION: A clinical guideline for OminMU has been established. The minMU can be increased by 1 MU for every 35 cGy of DPD without compromising plan quality for most cases analyzed in this study. Significant treatment time reduction of up to 56% was observed when the suggested OminMU is used.

Optimizing spot intensity with lower bound constraints for IMPT: Exposing shortcomings and introducing an enhanced strategy.

BACKGROUND: Intensity Modulated Proton Therapy (IMPT) is a sophisticated radiation treatment allowing for precise dose distributions. However, conventional spot selection strategies in IMPT face challenges, particularly with minimum monitor unit (MU) constraints, affecting planning quality and efficiency. PURPOSE: This study introduces an innovative Two-Stage Mixed Integer Linear Programming (MILP) method to optimize spot intensity in IMPT with Lower Bound (LB) constraints. This method seeks to improve treatment planning efficiency and precision, overcoming limitations of existing strategies. METHODS: Our approach evaluates prevalent IMPT spot selection strategies, identifying their limitations, especially concerning MU constraints. We integrated LB constraints into a MILP framework, using a novel three-phase strategy for spot pool selection, to enhance performance over traditional heuristic methods and L1 + L∞ strategies. The method's efficacy was tested in eight study cases, using Dose-Volume Histograms (DVHs), spot selection efficiency, and computation time analysis for benchmarking against established methods. RESULTS: The proposed method showed superior performance in DVH quality, adhering to LB constraints while maintaining high-quality treatment plans. It outperformed existing techniques in spot selection, reducing unnecessary spots and balancing precision with efficiency. Cases studies confirmed the method's effectiveness in producing clinically feasible plans with enhanced dose distributions and reduced hotspots, especially in cases with elevated LB constraints. CONCLUSIONS: Our Two-Stage MILP strategy signifies a significant advancement in IMPT treatment planning. By incorporating LB constraints directly into the optimization process, it achieves superior plan quality and deliverability compared to current methods. This approach is particularly advantageous in clinical settings requiring minimum spot number and high MU LB constraints, offering the potential for improved patient outcomes through more precise and efficient radiation therapy plans.

Prediction of the axillary lymph-node metastatic burden of breast cancer by 18F-FDG PET/CT-based radiomics.

BACKGROUND: The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT)-based radiomics in combination with ultrasound and clinical pathological features for predicting axillary lymph-node metastatic burden in breast cancer. METHODS: A retrospective analysis was conducted and involved 124 patients with pathologically confirmed early-stage breast cancer who had undergone 18F-FDG PET/CT examination. The ultrasound, PET/CT, and clinical pathological features of all patients were analysed, and radiomic features from PET images were extracted to establish a multi-parameter predictive model. RESULTS: The ultrasound lymph-node positivity rate and PET lymph-node positivity rate in the high nodal burden group were significantly higher than those in the low nodal burden group (χ2 = 19.867, p < 0.001; χ2 = 33.025, p < 0.001). There was a statistically significant difference in the PET-based radiomics score (RS) for predicting axillary lymph-node burden between the high and low lymph-node burden groups. (-1.04 ± 0.41 vs. -1.47 ± 0.41, t = -4.775, p < 0.001). The ultrasound lymph-node positivity (US_LNM) (odds ratio [OR] = 3.264, 95% confidence interval [CI] = 1.022-10.423), PET lymph-node positivity (PET_LNM) (OR = 14.242, 95% CI = 2.960-68.524), and RS (OR = 5.244, 95% CI = 3.16-20.896) are all independent factors associated with high lymph-node burden (p < 0.05). The area under the curve (AUC) of the multi-parameter (MultiP) model was 0.895, which was superior to those of US_LNM, PET_LNM, and RS models (AUC = 0.703, 0.814, 0.773, respectively), with statistically significant differences (Z = 2.888, 3.208, 3.804, respectively; p = 0.004, 0.002, < 0.001, respectively). Decision curve analysis indicated that the MultiP model provided a higher net benefit for all patients. CONCLUSION: A MultiP model based on PET-based radiomics was able to effectively predict axillary lymph-node metastatic burden in breast cancer. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (registration number: NCT05826197) on May 7, 2023.

A novel WNT10A variant impairs the homeostasis of alveolar bone mesenchymal stem cells.

OBJECTIVES: To explore the influence of a novel WNT10A variant on bone mineral density, proliferation, and osteogenic differentiation capacities of alveolar bone mesenchymal stem cells in humans. SUBJECTS AND METHODS: Whole-exome sequencing and Sanger sequencing were utilized to detect gene variants in a family with non-syndromic tooth agenesis (NSTA). The panoramic mandibular index was calculated on the proband with WNT10A variant and normal controls to evaluate bone mineral density. Alveolar bone mesenchymal stem cells from the proband with a novel WNT10A variant and normal controls were isolated and cultured, then proliferation and osteogenic differentiation capacities were evaluated and compared. RESULTS: We identified a novel WNT10A pathogenic missense variant (c.353A > G/p. Tyr118Cys) in a family with NSTA. The panoramic mandibular index of the proband implied a reduction in bone mineral density. Moreover, the proliferation and osteogenic differentiation capacities of alveolar bone mesenchymal stem cells from the proband with WNT10A Tyr118Cys variant were significantly decreased. CONCLUSIONS: Our findings broaden the spectrum of WNT10A variants in patients with non-syndromic oligodontia, suggest an association between WNT10A and the proliferation and osteogenic differentiation of alveolar bone mesenchymal stem cells, and demonstrate that WNT10A is involved in maintaining jaw bone homeostasis.

Tailoring photobiomodulation to enhance tissue regeneration.

Photobiomodulation (PBM), the use of biocompatible tissue-penetrating light to interact with intracellular chromophores to modulate the fates of cells and tissues, has emerged as a promising non-invasive approach to enhancing tissue regeneration. Unlike photodynamic or photothermal therapies that require the use of photothermal agents or photosensitizers, PBM treatment does not need external agents. With its non-harmful nature, PBM has demonstrated efficacy in enhancing molecular secretions and cellular functions relevant to tissue regeneration. The utilization of low-level light from various sources in PBM targets cytochrome c oxidase, leading to increased synthesis of adenosine triphosphate, induction of growth factor secretion, activation of signaling pathways, and promotion of direct or indirect gene expression. When integrated with stem cell populations, bioactive molecules or nanoparticles, or biomaterial scaffolds, PBM proves effective in significantly improving tissue regeneration. This review consolidates findings from in vitro, in vivo, and human clinical outcomes of both PBM alone and PBM-combined therapies in tissue regeneration applications. It encompasses the background of PBM invention, optimization of PBM parameters (such as wavelength, irradiation, and exposure time), and understanding of the mechanisms for PBM to enhance tissue regeneration. The comprehensive exploration concludes with insights into future directions and perspectives for the tissue regeneration applications of PBM.

Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

[Constructing a predictive model for the death risk of patients with septic shock based on supervised machine learning algorithms].

OBJECTIVE: To construct and validate the best predictive model for 28-day death risk in patients with septic shock based on different supervised machine learning algorithms. METHODS: The patients with septic shock meeting the Sepsis-3 criteria were selected from Medical Information Mart for Intensive Care-IV v2.0 (MIMIC-IV v2.0). According to the principle of random allocation, 70% of these patients were used as the training set, and 30% as the validation set. Relevant predictive variables were extracted from three aspects: demographic characteristics and basic vital signs, serum indicators within 24 hours of intensive care unit (ICU) admission and complications possibly affecting indicators, functional scoring and advanced life support. The predictive efficacy of models constructed using five mainstream machine learning algorithms including decision tree classification and regression tree (CART), random forest (RF), support vector machine (SVM), linear regression (LR), and super learner [SL; combined CART, RF and extreme gradient boosting (XGBoost)] for 28-day death in patients with septic shock was compared, and the best algorithm model was selected. The optimal predictive variables were determined by intersecting the results from LASSO regression, RF, and XGBoost algorithms, and a predictive model was constructed. The predictive efficacy of the model was validated by drawing receiver operator characteristic curve (ROC curve), the accuracy of the model was assessed using calibration curves, and the practicality of the model was verified through decision curve analysis (DCA). RESULTS: A total of 3 295 patients with septic shock were included, with 2 164 surviving and 1 131 dying within 28 days, resulting in a mortality of 34.32%. Of these, 2 307 were in the training set (with 792 deaths within 28 days, a mortality of 34.33%), and 988 in the validation set (with 339 deaths within 28 days, a mortality of 34.31%). Five machine learning models were established based on the training set data. After including variables at three aspects, the area under the ROC curve (AUC) of RF, SVM, and LR machine learning algorithm models for predicting 28-day death in septic shock patients in the validation set was 0.823 [95% confidence interval (95%CI) was 0.795-0.849], 0.823 (95%CI was 0.796-0.849), and 0.810 (95%CI was 0.782-0.838), respectively, which were higher than that of the CART algorithm model (AUC = 0.750, 95%CI was 0.717-0.782) and SL algorithm model (AUC = 0.756, 95%CI was 0.724-0.789). Thus above three algorithm models were determined to be the best algorithm models. After integrating variables from three aspects, 16 optimal predictive variables were identified through intersection by LASSO regression, RF, and XGBoost algorithms, including the highest pH value, the highest albumin (Alb), the highest body temperature, the lowest lactic acid (Lac), the highest Lac, the highest serum creatinine (SCr), the highest Ca2+, the lowest hemoglobin (Hb), the lowest white blood cell count (WBC), age, simplified acute physiology score III (SAPS III), the highest WBC, acute physiology score III (APS III), the lowest Na+, body mass index (BMI), and the shortest activated partial thromboplastin time (APTT) within 24 hours of ICU admission. ROC curve analysis showed that the Logistic regression model constructed with above 16 optimal predictive variables was the best predictive model, with an AUC of 0.806 (95%CI was 0.778-0.835) in the validation set. The calibration curve and DCA curve showed that this model had high accuracy and the highest net benefit could reach 0.3, which was significantly outperforming traditional models based on single functional score [APS III score, SAPS III score, and sequential organ failure assessment (SOFA) score] with AUC (95%CI) of 0.746 (0.715-0.778), 0.765 (0.734-0.796), and 0.625 (0.589-0.661), respectively. CONCLUSIONS: The Logistic regression model, constructed using 16 optimal predictive variables including pH value, Alb, body temperature, Lac, SCr, Ca2+, Hb, WBC, SAPS III score, APS III score, Na+, BMI, and APTT, is identified as the best predictive model for the 28-day death risk in patients with septic shock. Its performance is stable, with high discriminative ability and accuracy.

Shewanella phaeophyticola sp. nov. and Vibrio algarum sp. nov., isolated from marine brown algae.

Two Gram-stain-negative, rod-shaped bacteria, designated as strains KJ10-1T and KJ40-1T, were isolated from marine brown algae. Both strains were catalase-positive, oxidase-positive, and facultative aerobic. Strain KJ10-1T exhibited optimal growth at 25 °C, pH 7.0, and 3 % NaCl, whereas strain KJ40-1T showed optimal growth at 25 °C, pH 7.0, and 2 % NaCl. The respiratory quinones of strain KJ10-1T were ubiquinone-8, ubiquinone-7, menaquinone-7, and methylated menaquinone-7, while the respiratory quinone of strain KJ40-1T was only ubiquinone-8. As major fatty acids, strain KJ10-1T contained C16 : 0, C17 : 1 ω8c, iso-C15 : 0, and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and strain KJ40-1T contained C16 : 0 and summed features 3 and 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The major polar lipids in strain KJ10-1T were phosphatidylethanolamine, phosphatidylglycerol, and an unidentified aminolipid, whereas those in strain KJ40-1T were phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The DNA G+C contents of strains KJ10-1T and KJ40-1T were 42.1 and 40.8 mol%, respectively. Based on 16S rRNA gene sequences, strains KJ10-1T and KJ40-1T exhibited the closest relatedness to Shewanella saliphila MMS16-UL250T (98.6 %) and Vibrio rumoiensis S-1T (95.4 %), respectively. Phylogenetic analyses, based on both 16S rRNA and 92 housekeeping genes, showed that the strains formed distinct phylogenic lineages within the genera Shewanella and Vibrio. Digital DNA-DNA hybridization and orthologous average nucleotide identity values between strain KJ10-1T and other Shewanella species, as well as between strain KJ40-1T and other Vibrio species, were below the thresholds commonly accepted for prokaryotic species delineation. Based on the phenotypic, chemotaxonomic, and phylogenetic data, strains KJ10-1T and KJ40-1T represent novel species of the genera Shewanella and Vibrio, respectively, for which the names Shewanella phaeophyticola sp. nov. and Vibrio algarum sp. nov. are proposed, respectively. The type strains of S. phaeophyticola and V. algarum are KJ10-1T (=KACC 22589T=JCM 35409T) and KJ40-1T (=KACC 22588T=JCM 35410T), respectively.