Development and validation of a nomogram for predicting in-hospital survival rates of patients with COVID-19.

Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19). Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort. Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio (HR) = 1.539, 95 % confidence interval (CI): 1.027-2.306, P = 0.037], history of diabetes (HR = 1.741, 95 % CI: 1.253-2.420, P = 0.001), high APACHE II score (HR = 1.083, 95 % CI: 1.042-1.126, P < 0.001), sepsis (HR = 2.387, 95 % CI: 1.707-3.338, P < 0.001), high neutrophil-to-lymphocyte ratio (NLR) (HR = 1.010, 95 % CI: 1.003-1.017, P = 0.007), and high D-dimer level (HR = 1.005, 95 % CI: 1.001-1.009, P = 0.028) were independent risk factors for 14 d and 28 d survival rates, whereas COVID-19 vaccination (HR = 0.625, 95 % CI: 0.440-0.886, P = 0.008) was a protective factor affecting prognosis. ROC curve analysis showed that the area under the curve (AUC) of the 14 d and 28 d hospital survival rates in the training cohort was 0.765 (95 % CI: 0.641-0.923) and 0.814 (95 % CI: 0.702-0.938), respectively, and the AUC of the 14 d and 28 d hospital survival rates in the verification cohort was 0.898 (95 % CI: 0.765-0.962) and 0.875 (95 % CI: 0.741-0.945), respectively. The calibration curves of 14 d and 28 d hospital survival showed that the predicted probability of the model agreed well with the actual probability. Decision curve analysis (DCA) showed that the nomogram has high clinical application value. Conclusion: In-hospital survival rates of patients with COVID-19 were predicted using a nomogram, which will help clinicians in make appropriate clinical decisions.

Picrachinentins A-F, 14-Membered Cyclopeptide Alkaloid-Type Burpitides with Uncommon N-Terminal Modifications from Picrasma chinensis and Their Neuroprotective Activity.

Picrachinentins A-F (1-6, respectively), six novel cyclopeptide alkaloid-type burpitides (CPABs), were isolated and fully elucidated from the EtOH extract of the stems and leaves of Picrasma chinensis. Structurally, compounds 1-6 have a 14-membered paracyclophane ring system that was closed through an ether bond between the ß-hydroxy amino acid and tyrosine and modified with a 4,5-methylenedioxybenzoyloxy (MDBz, 3 and 5) or hexanoyl (Hexa, 1, 2, 4, and 6) group at the N-terminus. Interestingly, this is the first report on the isolation and characterization of CPABs from plants of the Simaroubaceae family. In addition, all compounds showed a neuroprotective effect against H2O2-damaged SH-SY5Y cells. Compound 1 was further investigated for its neuroprotective activities using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease animal model, and it dramatically improved MPTP-impaired motor behavioral performance. Biochemical analysis revealed compound 1 restored the tyrosine hydroxylase expression in the striatum of the MPTP-damaged mouse brain, which demonstrates its protective effect on dopaminergic neurons.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Experimental Study of the Mechanical Properties of Full-Scale Rubber Bearings at 23 °C, 0 °C, and -20 °C.

In this study, the effects of ambient temperature on the horizontal mechanical performance of isolated rubber bearings were investigated using high-speed reciprocating loading methods. A comprehensive series of 54 experimental trials are performed on the full-scale (900 mm-diameter) isolation rubber bearings, encompassing a range of temperatures (-20 °C, 0 °C, and 23 °C), shear pressures (50%, 100%, and 250%), and frequencies (0.20 Hz, 0.25 Hz, and 0.30 Hz). Because the compression-shear tests were conducted at high velocities and pressures (specifically, vertical compressive stress of 15 MPa), the equipment used in these tests was capable of generating substantial inertial and frictional forces. Appropriate correction methodologies for the precise determination of mechanical performance metrics for bearings are presented. Then, a comprehensive investigation of the effects of various loading conditions on the characteristic strength, post-yield stiffness, horizontal equivalent stiffness, and equivalent damping ratio of LRB900 (lead-core rubber bearings 900 mm-diameter) and LNR900 (linear natural rubber bearings 900 mm-diameter) is conducted. The empirical results show a discernible relationship between these characteristics and ambient temperature as the number of loading cycles increases, except for the equivalent damping ratio. Finally, empirical fitting formulations incorporating the influence of ambient temperature are presented for each performance indicator. These formulas are intended to assist designers in performing seismic design analyses by allowing them to take into consideration the effects of ambient temperature comprehensively.

Optical assembly of multi-particle arrays by opto-hydrodynamic binding of microparticles close to a one-dimensional chain of magnetic microparticles.

Two-dimensional materials possess a large number of interesting and important properties. Various methods have been developed to assemble two-dimensional aggregates. Assembly of colloidal particles can be achieved with laser-heating-induced thermal convective flow. In this paper, an opto-hydrodynamic binding method is proposed to assemble colloidal particles dispersed in a solution into multilayer structures. First, we use polystyrene (PS) microspheres to study the feasibility and characteristics of the assembly method. PS microspheres and monodispersed magnetic silica microspheres (SLEs) are dispersed in a solution to form a binary mixture system. Under the action of an external uniform magnetic field, SLEs in the solution form chains. An SLE chain is heated by a laser beam. Due to the photothermal effect, the SLE chain is heated to produce a thermal gradient, resulting in thermal convection. The thermal convection drives the PS beads to move toward the heated SLE chain and finally stably assemble into multilayer aggregates on both sides of the SLE chain. The laser power affects the speed and result of the assembly. When the laser power is constant, the degree of constraint of the PS microbeads in different layers is also different. At the same time, this method can also assemble the biological cells, and the spacing of different layers of cells can be changed by changing the electrolyte concentration of the solution. Our work provides an approach to assembling colloidal particles and cells, which has a potential application in the analysis of the collective dynamics of microparticles and microbes.

Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

An integrated analysis revealing the angiogenic function of TP53I11 in tumor microenvironment.

Despite growing evidence suggesting an important contribution of Tumor Protein P53 Inducible Protein 11 (TP53I11) in cancer progression, the role of TP53I11 remains unclear. Our first pan-cancer analysis of TP53I11 showed some tumor tissues displayed reduced TP53I11 expression compared to normal tissues, while others exhibited high TP53I11 expression. Meanwhile, TP53I11 expression carries a particular pan-cancer risk, as high TP53I11 expression levels are detrimental to survival for BRCA, KIRP, MESO, and UVM, but to beneficial survival for KIRC. We demonstrated that TP53I11 expression negatively correlates with DNA methylation in most cancers, and the S14 residue of TP53I11 is phosphorylated in several cancer types. Additionally, TP53I11 was found to be associated with endothelial cells in pan-cancer, and functional enrichment analysis provided strong evidence for its role in tumor angiogenesis. In vitro angiogenesis assays confirmed that TP53I11 can promote angiogenic function of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistic investigations reveal that TP53I11 is transcriptionally up-regulated by HIF2A under hypoxia.

Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management.

Association of Concomitant MRI-Determined Anterolateral Complex Injury With Quantitative Measurements of Altered Rotational Tibiofemoral Position on MRI in Patients With ACL Injury.

Background: Reduced graft failure rates have been reported after anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex (ALC) augmentation. However, the preoperative diagnosis of concomitant ALC injury remains a clinical challenge. Purpose: To identify the altered rotational tibiofemoral position on magnetic resonance imaging (MRI) in ACL-injured patients with concomitant ALC injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Based on the evaluation of ALC abnormalities on MRI scans by experienced surgeons, 123 patients with nonchronic (<3 months) ACL injury confirmed by arthroscopy were included. The patients were divided into 2 groups-an ALC-injured group (n = 57) and an ALC-intact group (n = 66). The altered rotational tibiofemoral position was evaluated and compared by quantitatively measuring internal rotational tibial subluxation (IRTS) and axial internal tibial rotation (ITRa) on MRI. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed to identify the factors associated with concomitant MRI-determined ALC injury. Results: The ALC-injured group showed significantly increased IRTS (P < .001), ITRa (P < .001), lateral anterior tibial subluxation (ATS) (P < .001), and global ATS (GATS) (P = .002) compared with the ALC-intact group, while no significant difference in medial ATS (P = .810) was observed. A strong positive correlation was identified between IRTS and ITRa (rP = 0.809; P < .001). Multivariate analyses revealed that IRTS (P < .001) and GATS (P = .016) were associated factors for the presence of concomitant MRI-determined ALC injury. IRTS (area under the curve [AUC] = 0.734) was more strongly associated with the outcome than GATS (AUC = 0.658) in ROC analyses, suggesting a more significant internal rotational subluxation than anterior subluxation of the tibia. An IRTS threshold of 3.1 mm demonstrated a specificity of 84.2% for indicating the presence of concomitant MRI-determined ALC injury. Conclusion: The presence of concomitant MRI-determined ALC injury in ACL-injured patients was associated with a significant increase in IRTS and ITRa compared with those with intact ALC, indicating that these MRI measurements of the altered rotational tibiofemoral position could serve as potential quantifiable indicators for identifying concomitant ALC injury in clinical practice.

Engineering of Bacillus thuringiensis Cry2Ab toxin for improved insecticidal activity.

Bacillus thuringiensis Cry2Ab toxin was a widely used bioinsecticide to control lepidopteran pests all over the world. In the present study, engineering of Bacillus thuringiensis Cry2Ab toxin was performed for improved insecticidal activity using site-specific saturation mutation. Variants L183I were screened with lower LC50 (0.129 µg/cm2) against P. xylostella when compared to wild-type Cry2Ab (0.267 µg/cm2). To investigate the molecular mechanism behind the enhanced activity of variant L183I, the activation, oligomerization and pore-formation activities of L183I were evaluated, using wild-type Cry2Ab as a control. The results demonstrated that the proteolytic activation of L183I was the same as that of wild-type Cry2Ab. However, variant L183I displayed higher oligomerization and pore-formation activities, which was consistence with its increased insecticidal activity. The current study demonstrated that the insecticidal activity of Cry2Ab toxin could be assessed using oligomerization and pore-formation activities, and the screened variant L183I with improved activity might contribute to Cry2Ab toxin's future application.

Inhibiting the m6A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown. Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition. Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression. Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

Effects of fertilizer application on the growth of Stranvaesia davidiana D. seedlings.

Wild plants represent a potential source of urban landscape trees. Stranvaesia davidiana Dcne. is a member of the Stranvaesia Lindl. Genus, which belongs to family Rosaceae Juss. It has great ornamental value. It can contribute to urban color foliage and fruit species. However, the most effective fertilizer application strategy required for its cultivation is unknown. Therefore, we conducted an orthogonal experiment to investigate the fertilizer type and level (pure nitrogen) using ten experimental groups, including an untreated control group. Pot experiments were used to determine the growth indices of seedlings, including plant height, basal diameter, and chlorophyll content post-fertilizer treatment. This study explored the most appropriate fertiler application model for the growth of S. davidiana seedlings. The results revealed that enhanced seedling growth depended on the type and amount of fertilizer used, and their interaction. Fertilizer application increased the plant height by 2.67 cm to 12.26 cm, basal diameter by 0.39 cm to 0.75 cm, and chlorophyll content by 5.66 to 19.86. Among the different types of fertilizer, organic fertilizer increased the plant height by 0.42 cm to 9.59 cm and basal diameter by 0.01 cm to 0.05 cm, compared with the control group. Organic fertilizer had the maximum effect on seedling growth, especially at medium levels. The total growth of basal diameter and chlorophyll content was 1.58 ± 0.04 cm and 39.53 ± 2.37, respectively. Basal diameter is the most critical index in seedling reproduction . The study results suggest that the application of 4.06 g of organic fertilizer per plant was the most effective, and served as a basis for further field trials.

N-acetylcysteine and Hydroxychloroquine Ameliorate ADMA-Induced Fetal Growth Restriction in Mice via Regulating Oxidative Stress and Autophagy.

Fetal growth restriction (FGR) seriously threatens perinatal health. The main cause of FGR is placental malperfusion, but the specific mechanism is still unclear, and there is no effective treatment for FGR. We constructed a FGR mouse model by adding exogenous asymmetric dimethylarginine (ADMA) through in vivo experiments and found that ADMA could cause placental dysplasia and induce the occurrence of FGR. Compared with the control group, reactive oxygen species (ROS) production in the placenta was increased in mice with FGR, and the expression of autophagy-related proteins p-AKT/AKT, p-mTOR/mTOR, and P62 was significantly decreased, while the expression of Beclin-1 and LC3-II was significantly increased in the FGR group. Furthermore, ADMA had a favorable effect in promoting the formation of autophagosomes. Hydroxychloroquine (HCQ) and N-acetylcysteine (NAC) improved ADMA-induced disorders of placental development and alleviated ADMA-induced FGR. This study found that ADMA could cause excessive autophagy of trophoblasts by increasing the level of oxidative stress, ultimately leading to the occurrence of FGR, and HCQ and NAC had therapeutic effects on ADMA-induced FGR.

The Crosstalk Between Immune Cells After Intracerebral Hemorrhage.

The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood-brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve.

Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps.

Objective: To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Methods: The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S-transferase 1 (MGST1) were examined using quantitative real-time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients. Results: The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve. Conclusion: These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

[Unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly].

OBJECTIVE: To investigate the clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the Interlaminar Endoscopic Surgical System(iLESSYS) Delta for the treatment of lumbar spinal stenosis (LSS) in the elderly. METHODS: Total of 29 patients with LSS treated with the iLESSYS Delta from December 2018 to January 2021 were retrospectively analyzed, including 12 males and 17 females with an average age of (71.52±10.82) years old ranging from 63 to 83 years old. All patients had definite intermittent claudication, mainly neurogenic symptoms of both lower limbs. All patients had single-level spinal stenosis, including L3,4 5 cases, L4,5 21 cases, and L5S1 3 cases. Visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified Macnab assessment criteria were used to evaluate pain, low back pain dysfunction index and clinical efficacy, respectively. RESULTS: All 29 cases were successfully completed. The operation time was (73.45±5.89) min, the intraoperative blood loss was (9.93±0.83) ml, the hospital stay was (4.03±0.41) days, and the follow-up was more than 12 months. The VAS scores of low back pain before surgery and 1 day, 1 month, 3 months, 1 year after surgery were 2.31±0.88, 1.45±0.62, 1.21±0.61, 1.10±0.55, 1.03±0.49;VAS of leg pain were 6.48±0.49 0.56, 1.97±0.61, 1.31±0.59, 1.17±0.59, 1.10±0.55;ODI scores were 38.41±2.74, 18.14±1.17, 5.17±0.53, 5.07±0.45, 4.90±0.48;low back and leg pain VAS score and ODI score have statistically significant differences between preoperative and postoperative follow-up time points (P<0.05). The MacNab efficacy evaluation at 1-year follow-up:excellent in 22 cases, good in 5 cases and fair in 2 cases. CONCLUSION: The clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly is satisfactory, with the advantages of less trauma and less bleeding, large microscopic operation space, sufficient decompression, and ideal post-operative recovery, and at the same time, it can minimize the damage to the stable structure of the lumbar spine, which is an ideal surgical method for the treatment of elderly lumbar spinal stenosis.

Imidazolone as an Amide Bioisostere in the Development of ß-1,3-N-Acetylglucosaminyltransferase 2 (B3GNT2) Inhibitors.

B3GNT2 is responsible for elongation of cell surface long-chain polylactosamine, which influences the regulation of the immune response, making it an attractive target for immunomodulation. In the development of amide containing B3GNT2 inhibitors guided by structure-based drug design, imidazolones were found to successfully serve as amide bioisosteres. This novel imidazolone isosteric strategy alleviated torsional strain of the amide bond on binding to B3GNT2 and improved potency, isoform selectivity, as well as certain physicochemical and pharmacokinetic properties. Herein, we present the synthesis, SAR, X-ray cocrystal structures, and in vivo PK properties of imidazol-4-ones in the context of B3GNT2 inhibition.

Impacts of physiological characteristics and human activities on the species distribution models of orchids taking the Hengduan Mountains as a case.

The biogeography research of orchids through species distribution models (SDMs), a vital tool in the biogeography field, is critical to understanding the fundamental geographic distribution patterns and identifying conservation priorities. The correspondence between species occurrence and environmental information is crucial to the model's performance. However, ecological preferences unique to different orchid species, such as their life forms, are often overlooked during the modeling process. This oversight can introduce bias and increase model uncertainty. Additionally, human activities, as an important potential predictor, have not been quantified in any orchid SDMs. Taking the Hengduan Mountains as an example, we preprocessed all orchid species' occurrences based on physiological characteristics. Choosing five spatial factors related to human activities to quantify the interference and enter into models as HI factor. Using different modeling methods (GLM, MaxEnt, and RF) and evaluation indices (AUC, TSS, and Kappa), diverse modeling strategies have been constructed in the study. A double-ranking method has been adopted to select the critical orchid distribution regions. The results showed that classification models based on physiological characteristics significantly improved the model's accuracy while adding the HI factor had the same effect but the absence of enough significance. Suitability maps indicated that highly heterogeneous mountainous areas were vital for the distribution of orchids in the Hengduan Mountains. Different distribution patterns and critical regions existed between various orchid life forms geographically - terrestrial orchids were dominant in the mountain, and mycoherterophical orchids were primarily located in the north, more influenced by vegetation and temperature. Critical regions of epiphytic orchids were in the south due to a greater dependence on precipitation and temperature. These studies are informative for understanding the orchids' geographic distribution patterns in the Hengduan Mountains, promoting conservation and providing references for similar research beyond orchids.

Favorable impact of a novel endoscopic auxiliary system (NEAS) on fluoroscopy-guided lithotripsy for difficult bile duct stones: A pilot study.

OBJECTIVES: Laser lithotripsy under fluoroscopic guidance is difficult to perform and risky due to its invisibility. In this study we aimed to investigate the efficacy and safety of a novel endoscopic auxiliary system (NEAS)-assisted lithotripsy under fluoroscopy for treating difficult common bile duct (CBD) stones. METHODS: Patients with difficult CBD stones who were treated with NEAS-assisted laser lithotripsy (NEAS group) or conventional mechanical lithotripsy (ML) under fluoroscopy (ML group) were retrospectively evaluated. The primary outcome was the complete stone clearance rate and the secondary outcomes included operation time, complications, and medical cost. RESULTS: Seventeen patients were treated with NEAS-assisted laser lithotripsy and 144 patients underwent ML. Using the propensity score matching analysis, 17 pairs of cases treated with NEAS-assisted lithotripsy and ML were included. Patients in the NEAS group showed a higher stone clearance rate than the ML group (94.1% vs 58.8%, P = 0.039), as well as shorter operation time (41.9 min vs 49.4 min, P < 0.001) and lower medical cost (USD 4607 vs USD 5014, P < 0.001). There was no significant difference in the complication rate between the two groups (5.9% vs 17.6%, P = 0.601). CONCLUSION: NEAS-assisted fluoroscopy-guided laser lithotripsy is feasible and safe, which may be a promising technique in fluoroscopy-guided laser lithotripsy for difficult CBD stones.

Hyperglycemia-regulated tRNA-derived fragment tRF-3001a propels neurovascular dysfunction in diabetic mice.

Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived RNA fragment, tRF-3001a, is significantly upregulated under diabetic conditions. tRF-3001a downregulation inhibits Müller cell activation, suppresses endothelial angiogenic effects, and protects against high-glucose-induced retinal ganglion cell injury in vitro. Furthermore, tRF-3001a downregulation alleviates retinal vascular dysfunction, inhibits retinal reactive gliosis, facilitates retinal ganglion cell survival, and preserves visual function and visually guided behaviors in STZ-induced diabetic mice and db/db diabetic mice. Mechanistically, tRF-3001a regulates neurovascular dysfunction in a microRNA-like mechanism by targeting GSK3B. Clinically, tRF-3001a is upregulated in aqueous humor (AH) samples of DR patients. tRF-3001a downregulation inhibits DR-induced human retinal vascular endothelial cell and Müller cell dysfunction in vitro and DR-induced retinal neurovascular dysfunction in C57BL/6J mice. Thus, targeting tRF-3001a-mediated signaling is a promising strategy for the concurrent treatment of vasculopathy and neuropathy in diabetes mellitus.