Predictive value of risk factors for bladder dysfunction in Chinese patients with type 2 diabetes mellitus: A case-control study.

OBJECTIVE: To analyze risk factors associated with bladder dysfunction in patients with type 2 diabetes mellitus (T2DM) and to construct a prediction model for early prediction of diabetic bladder dysfunction (DBD). METHODS: We included hospitalized patients with T2DM from the endocrinology department of Shenzhen Hospital, Southern Medical University, Shenzhen, China, from January 2019 to 2022. Factors associated with DBD in bivariate analysis with a p < 0.05 were included in a multivariate logistic regression analysis. Multivariate logistic regression analysis was used to determine independent risk factors and to construct a prediction model. The prediction model was presented as the model formula. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above risk factors and the prediction model for DBD. The model was internally verified by Boostrap resampling 1000 times. RESULTS: Two hundred and eleven patients were included in this study, and they were divided into the DBD group (n = 101) and the non-DBD group (n = 110). Eight variables showed significant significance in the bivariate analysis, including age, diabetic peripheral neuropathy (DPN), glycated hemoglobin (HbA1c), urinary microalbumin (mALB), red blood cell count (RBC), white blood cell count (WBC), absolute neutrophil count (ANC), percentage of monocyte (Mono%). Furthermore, multivariate logistic regression analysis revealed that age (OR [95% CI]: 1.077 [1.042-1.112]), p < 0.001; DPN (OR [95% CI]: 2.373 [1.013-5.561]), p = 0.047; HbA1c (OR [95% CI]: 1.170 [1.029-1.330]), p = 0.017 and ANC (OR [95% CI]: 1.234 [1.059-1.438]), p = 0.007 were independent risk factors for the DBD. The prediction model formula was Logit (p) = -6.611 + 0.074 age + 0.864 DPN + 0.157 HbA 1 c + 0.078 ANC. The area under the ROC curve (AUC) for the four risk factors were 0.676, 0.582, 0.618, and 0.674, respectively. The prediction model predicted DBD with higher accuracy than the individual risk factors, AUC = 0.817 (95% CI: 0.757-0.877), and the sensitivity and specificity were 88.1% and 50.0%, respectively. The model internal validation results showed that the AUC = 0.804 (95% CI: 0.707-0.901), and the calibration curve is close to the ideal diagonal line. CONCLUSIONS: Age, DPN, HbA1c, and ANC were risk factors for DBD. The prediction model constructed based on the four risk factors had a good predictive value for predicting the occurrence of DBD.

Quality and spatial intensity distribution characteristics of short-exposure spot images of a supercontinuum laser in a turbulent atmosphere.

In this study, considering the combined effects of atmospheric attenuation and turbulence, we examine the spot quality and spatial intensity distribution characteristics of a supercontinuum (SC) laser propagating in a turbulent atmosphere using the multi-layer phase-screen method. An increase in turbulence strength or a decrease in the initial beam radius resulted in a greater impact of the atmospheric turbulence on the SC laser. A decrease in source coherence results in the deterioration of the image quality of the far-field spot. Under moderate to strong turbulence, the scintillation index decreased as the source coherence decreased; however, the opposite trend was observed under weak turbulence. These results are significant for the advancement and optimization of SC laser systems.

Differential renal proteomics analysis in a novel rat model of iodinated contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI), which occurs after the use of iodinated contrast media, has become the third leading cause of hospital-acquired acute kidney injury (AKI). It is associated with prolonged hospitalization and increased risks of end-stage renal disease and mortality. The pathogenesis of CI-AKI is unclear and effective treatments are lacking. By comparing different post-nephrectomy times and dehydration times, we constructed a new, short-course CI-AKI model using dehydration for 24 h two weeks after unilateral nephrectomy. We found that the low-osmolality contrast media iohexol caused more severe renal function decline, renal morphological damage, and mitochondrial ultrastructural alterations compared to the iso-osmolality contrast media iodixanol. The shotgun proteomics based on Tandem Mass Tag (TMT) was used to conduct proteomics research on renal tissue in the new CI-AKI model, and 604 distinct proteins were identified, mainly involving complement and coagulation cascade, COVID-19, PPAR signalling pathway, mineral absorption, cholesterol metabolism, ferroptosis, staphylococcus aureus infection, systemic lupus erythematosus, folate biosynthesis, and proximal tubule bicarbonate reclamation. Then, using parallel reaction monitoring (PRM), we validate 16 candidate proteins, of which five were novel candidates (Serpina1, Apoa1, F2, Plg, Hrg) previously unrelated to AKI and associated with an acute response as well as fibrinolysis. The pathway analysis and 16 candidate proteins may help to discover new mechanisms in the pathogenesis of CI-AKI, allowing for early diagnosis and outcome prediction.

A Neuropeptide Y/F-like Polypeptide Derived from the Transcriptome of Turbinaria peltata Suppresses LPS-Induced Astrocytic Inflammation.

Neuropeptides are a group of neuronal signaling molecules that regulate physiological and behavioral processes in animals. Here, we used in silico mining to predict the polypeptide composition of available transcriptomic data of Turbinaria peltata. In total, 118 transcripts encoding putative peptide precursors were discovered. One neuropeptide Y/F-like peptide, named TpNPY, was identified and selected for in silico structural, in silico binding, and pharmacological studies. In our study, the anti-inflammation effect of TpNPY was evaluated using an LPS-stimulated C8-D1A astrocyte cell model. Our results demonstrated that TpNPY, at 0.75-3 µM, inhibited LPS-induced NO production and reduced the expression of iNOS in a dose-dependent manner. Furthermore, TpNPY reduced the secretion of proinflammatory cytokines. Additionally, treatment with TpNPY reduced LPS-mediated elevation of ROS production and the intracellular calcium concentration. Further investigation revealed that TpNPY downregulated the IKK/IκB/NF-κB signaling pathway and inhibited expression of the NLRP3 inflammasome. Through molecular docking and using an NPY receptor antagonist, TpNPY was shown to have the ability to interact with the NPY Y1 receptor. On the basis of these findings, we concluded that TpNPY might prevent LPS-induced injury in astrocytes through activation of the NPY-Y1R.

Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7.

INTRODUCTION: Transforming growth factor-ß (TGF-ß), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. OBJECTIVE: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. METHODS: HK-2 cells were induced with 5 ng/mL TGF-ß1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-ß1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-ß1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. RESULTS: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-ß1-induced cells. CONCLUSION: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.

The epidemiology and clinical information about COVID-19.

In December 2019, pneumonia of unknown cause occurred in Wuhan, Hubei Province, China. On 7 January 2020, a novel coronavirus, named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was identified in the throat swab sample of one patient. The World Health Organization (WHO) announced the epidemic disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). Currently, COVID-19 has spread widely around the world, affecting more than seventy countries. China, with a huge burden of this disease, has taken strong measures to control the spread and improve the curative rate of COVID-19. In this review, we summarized the epidemiological characteristics, clinical features, diagnosis, treatment, and prognosis of COVID-19. A comprehensive understanding will help to control the disease.

Role of Artificial Intelligence in Kidney Disease.

Artificial intelligence (AI), as an advanced science technology, has been widely used in medical fields to promote medical development, mainly applied to early detections, disease diagnoses, and management. Owing to the huge number of patients, kidney disease remains a global health problem. Challenges remain in its diagnosis and treatment. AI could take individual conditions into account, produce suitable decisions and promise to make great strides in kidney disease management. Here, we review the current studies of AI applications in kidney disease in alerting systems, diagnostic assistance, guiding treatment and evaluating prognosis. Although the number of studies related to AI applications in kidney disease is small, the potential of AI in the management of kidney disease is well recognized by clinicians; AI will greatly enhance clinicians' capacity in their clinical practice in the future.

Toxicity assessment of p-choroaniline on Platymonas subcordiformis and its biodegradation.

The use of p-chloroaniline (PCA) in various aspects leads to its existence and accumulation in the environment. Relevant researches showed that PCA was a prime toxic pollutant that had imposed a serious risk to public health and the environment. This paper investigated the toxicity effects of PCA on Platymonas subcordiformis (P. subcordiformis) and the biodegradation of PCA by the marine microalga. In the toxicity experiments, the EC50 of PCA on P. subcordiformis at 24 h, 48 h, 72 h and 96 h was 41.42, 24.04, 17.15 and 13.05 mg L-1, respectively. The pigment parameters including chlorophyll a, chlorophyll b, carotenoids, photosynthetic O2 release rate, respiration O2 consumption rate and the chlorophyll fluorescence parameters including Fv/Fm, ETR and qP decreased greatly while antioxidant enzyme activities (SOD, CAT) and the chlorophyll fluorescence parameter NPQ increased when P. subcordiformis exposed to PCA compared with the control group. Fv/Fm would be a suitable indicator for assessing the toxicity of PCA in marine environment based on the analysis of Pearson's correlation coefficient and Integrated Biomarker Response (IBR). The degradation assay in P. subcordiformis indicated that the green marine microalga had the ability to remove and degrade PCA, and the order of removal and degradation proportion of PCA was 2 mg L-1 > 5 mg L-1>10 mg L-1. The maximum removal and biodegradation percentage was 54% and 34%, respectively.

Novel neurotoxic peptides from Protopalythoa variabilis virtually interact with voltage-gated sodium channel and display anti-epilepsy and neuroprotective activities in zebrafish.

We previously reported a novel toxic peptide identified from the anthozoan Protopalythoa variabilis transcriptome which is homologous to a novel structural type of sodium channel toxin isolated from a parental species (Palythoa caribaeorum). The peptide was named, according to its homologous, as Pp V-shape α-helical peptide (PpVα) in the present study. Through molecular docking and dynamics simulation, linear and hairpin folded PpVα peptides were shown to be potential voltage-gated sodium channel blockers. Nowadays, sodium channel blockers have been the mainstream of the pharmacological management of epileptic seizures. Also, sodium channel blockers could promote neuronal survival by reducing sodium influx and reducing the likelihood of calcium importation resulting in suppressing microglial activation and protecting dopaminergic neurons from degeneration. The folded PpVα peptide could decrease pentylenetetrazol (PTZ)-induced c-fos and npas4a expression level leading to reverse PTZ-induced locomotor hyperactivity in zebrafish model. In vitro, the folded PpVα peptide protected PC12 cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity via activating heme oxygenase-1 (HO-1) and attenuating inducible nitric oxide synthase (iNOS) expression. In vivo, PpVα peptide suppressed the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish and, importantly, prevented the 6-OHDA-induced excessive ROS generation and subsequent dopaminergic neurons loss. This study indicates that the single S-S bond folded PpVα peptide arises as a new structural template to develop sodium channel blockers and provides an insight on the peptide discovery from cnidarian transcriptome to potentially manage epilepsy and neurodegenerative disorders.

Toxicity effects of p-choroaniline on the growth, photosynthesis, respiration capacity and antioxidant enzyme activities of a diatom, Phaeodactylum tricornutu.

The environmental risk issues of p-choroaniline have been concerned by the widespread application and transportation of this important chemical intermediate. The information about the toxicity of p-chloroaniline was mainly concentrated on freshwater organisms while the current knowledge on marine organisms was scarce yet. In this study, acute toxicity and toxic physiology characteristic of p-chloroaniline to Phaeodactylum tricornutum (P. tricornutum) were first determined. In the acute experiments, the effect of the p-choroaniline to P. tricornutum showed time- and dose-dependent response, which the half maximum effective concentration (EC50) at 24 h, 48 h and 96 h was 35.35, 20.10 and 10.00 mgL-1, respectively. Toxic physiology assays in P. tricornutum indicated that the p-choroaniline induced significant changes of photosynthetic pigments (Chl-a, Chl-b, Caro, Chl-a/b and Chl-(a+b)/Caro), Chlorophyll fluorescence parameters (Fv/Fm, ETR, qP and NPQ), rates of photosynthetic O2 release and respiration O2 consumption, and antioxidant enzyme activities (SOD, CAT). The obvious decrease of Fv/Fm, ETR and chl-a in low p-choroaniline treatments (≤ 5.00 mgL-1) compared with the control could be observed, which implied that these parameters could be taken as sensitive indicators for the environmental assessment. Meanwhile, the activities of SOD and CAT significant increase in p-choroaniline stress after 24 h and the extent of the increase has fallen after 96 h. These toxicity data obtained here might provide available basic data for the ecological risk assessment of p-choroaniline pollution.

Comparison of lipid profiles and inflammation in pre- and post-menopausal women with cerebral infarction and the role of atorvastatin in such populations.

BACKGROUND: The risks of atherosclerotic cardiovascular and cerebrovascular diseases in women rapidly increase with age in post-menopausal women. We aimed to investigate the lipid profiles in peri-menopausal women with cerebral infarction and to explore the effects of atorvastatin intervention. METHODS: We collected women aged 40-60 with cerebral infarction between January 2013 and December 2016. Atorvastatin was applied for 6 months in all included patients. Blood lipid profiles, serum pro-inflammation cytokines, intracranial plaque and NIH stroke scale (NIHSS) scores were evaluated before and after atorvastatin treatment. RESULTS: Totally 210 patients were included. Before atorvastatin treatment, post-menopausal patients had significantly higher levels of triglyceride, cholesterol, low-density lipoprotein and a reduced level of high-density lipoprotein than those in pre-menopausal patients. Blood levels of pro-inflammatory cytokines including interleukin (IL)-1, IL-6 and tumor necrosis factor-α were higher in post-menopausal patients, who had larger intracranial plaques than pre-menopausal patients. Consistently, post-menopausal patients had higher NIHSS scores than pre-menopausal ones. Atorvastatin reduced NIHSS scores and improved dyslipidemia in patients and eliminated the differences of these parameters between pre- and post-menopausal patients. CONCLUSIONS: Post-menopausal patients were severer than pre-menopausal patients in terms of dyslipidemia, systemic inflammation and NIHSS scores. Atorvastatin may be beneficial for women with cerebral infarction.

The immune-regulating effect of Xiao'er Qixingcha in constipated mice induced by high-heat and high-protein diet.

BACKGROUND: Xiao'er Qixingcha (EXQ) has been extensively applied to relieve dyspepsia and constipation in children for hundreds of years in China. However, the therapeutic mechanism underlying its efficacy remained to be defined. The present study aimed to clarify the possible laxative and immune-regulating effects of EXQ on two models of experimental constipation in mice, which mimicked the pediatric constipation caused by high-heat and high-protein diet (HHPD). METHODS: The two models of constipated mice were induced by HHPD or HHPD + atropine respectively. To investigate the laxative and immune-regulating activities of EXQ, animals were treated with three doses of EXQ (0.75, 1.5 and 3 g/kg) for 7 consecutive days. The fecal output parameters (number and weight), weight of intestinal content and, the thymus and spleen indexes were measured. The levels of sIgA, IL-10, TNF-α and LPS in colon and serum were determined by ELISA. Furthermore, the pathological changes of colon tissue were examined after routine H&E staining. RESULTS: Both HHPD and HHPD + atropine treatments obviously inhibited the fecal output and reduced the colonic sIgA, prominently increased the levels of IL-10 and TNF-α in colonic tissue and elevated the contents of LPS in serum and colonic tissues. In contrast, oral administration of EXQ significantly improved the feces characters and dose-dependently decreased the intestinal changes in both models. In HHPD model test, EXQ efficaciously boosted the sIgA level in a dose-dependent manner, significantly elicited decreases in TNF-α and IL-10 levels, and evidently decreased the spleen and thymus indexes. In HHPD + atropine model test, EXQ treatment reversed the pathological changes by not only dramatically decreasing the spleen index and the levels of LPS and IL-10, but also markedly elevating the thymus index. Furthermore, microscopic observation revealed that EXQ treatment maintained the integrity of colonic mucosa, and protected the colonic tissues from inflammation in the both models. CONCLUSIONS: EXQ exhibited prominent laxative activity and effectively protected the colonic mucosal barrier in two models of constipated mice, of which the mechanism might be closely associated with its propulsive and immune-regulating properties. The current results not only validated the rationale for the clinical application of EXQ in pediatric constipation related symptoms, but also threw new light on the immune-inflammatory responses accompanied with chronic constipation pathology.

microRNA-340 induces apoptosis by downregulation of BAG3 in ovarian cancer SKOV3 cells.

Aberrant expression of miR-340 has been found in several kinds of cancers including ovarian cancer. Pro-apoptotic and anti-metastasis roles of miR-340 in ovarian cancer have also been reported; however, the underling molecular mechanisms by which miR-340 suppresses ovarian cancer are still unclear. This study focused on the role and molecular mechanism of miR-340 in ovarian cancer. Human ovarian carcinoma SKOV3 cells were used and transfected with miR-340 mimic, miR-340 inhibitor and their correspondingly negative controls (mimic control and inhibitor control). Thereafter, cell viability, apoptosis, and the expressions of apoptosis-associated factors and BAG3 were respectively assessed by MTT assay, flow cytometry, qRT-PCR and Western blotting. SKOV3 cells were then co-transfected with miR-340 inhibitor and BAG3 targeted siRNA, then cell viability, apoptosis and the expression of apoptosis-associated factors were retested. Besides, the expressions of main factors in PI3K/AKT pathway were detected. Overexpression of miR-340 suppressed BAG3 cells viability (P < 0.05), but improved apoptosis (P < 0.001). BAG3 was negatively regulated by miR-340 (P < 0.05 or P < 0.01). BAG3 silence significantly induced cell apoptosis (P < 0.001), and abolished miR-340 suppression-induced increase in cell viability (P < 0.001). Besides, BAG3 silence abolished miR-340 suppression-induced activation of PI3K and AKT. This study revealed the tumor suppressive role of miR-340 in SKOV3 cells by negative regulation of BAG3. PI3K/AKT pathway might be involved in the regulation of miR-340 and BAG3.

Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation.

Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1ß, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent.

[Baseline Correction Algorithm for Raman Spectroscopy Based on Non-Uniform B-Spline].

As one of the necessary steps for data processing of Raman spectroscopy, baseline correction is commonly used to eliminate the interference of fluorescence spectra. The traditional baseline correction algorithm based on polynomial fitting is simple and easy to implement, but its flexibility is poor due to the uncertain fitting order. In this paper, instead of using polynomial fitting, non-uniform B-spline is proposed to overcome the shortcomings of the traditional method. Based on the advantages of the traditional algorithm, the node vector of non-uniform B-spline is fixed adaptively using the peak position of the original Raman spectrum, and then the baseline is fitted with the fixed order. In order to verify this algorithm, the Raman spectra of parathion-methyl and colza oil are detected and their baselines are corrected using this algorithm, the result is made comparison with two other baseline correction algorithms. The experimental results show that the effect of baseline correction is improved by using this algorithm with a fixed fitting order and less parameters, and there is no over or under fitting phenomenon. Therefore, non-uniform B-spline is proved to be an effective baseline correction algorithm of Raman spectroscopy.

[Research of the Raman Signal De-Noising Method Based on Feature Extraction].

To improve time resolution of the Raman measurement system, we need to adopt short scanning time. In this case, the weak Raman signal with vibrational spectrum of the molecular structure is easily to be buried by the high background noise, which influences the further analysis seriously. So it is necessary to de-noise the raw Raman signals. Conventional methods manage to de-noise signal by means of smoothing or averaging based on the difference between signal and noise in frequency characteristic or statistical features. They are commonly applied in the situation where the background noise is not so strong, and cannot give satisfactory results to the Raman signals with low signal-to-noise ratio. In this paper, the algorithm proposed detects peak positions and get peak half-width based on wavelet transform, and then reconstructs the Raman signals by least square fitting algorithm with characteristic parameters obtained, which extracts the useful signal from high background noise efficiently. In the simulation, the Raman curve fitted by the proposed algorithm was smooth, and the peak positions obtained were accurate, so the signal-to-noise ratio improved significantly. In the experiment, we adopted this algorithm to de-noise the tested Raman signal of Cefuroxime Axetil Tablets and Roxithromycin, respectively. The peak positions, peak half-width and amplitude were obtained and proved to be accurate. Therefore, the useful pure Raman signal could be recovered from the high background noise efficiently by the proposed algorithm, which improved the time resolution of Raman system. Both the simulation and the experiment showed that the proposed method could be easily performed with only a few parameters. Comparing with conventional methods, it could achieve satisfactory results under high background noise and provide accurate and reliable information for further analysis.

Andrographolide sodium bisulphite-induced inactivation of urease: inhibitory potency, kinetics and mechanism.

BACKGROUND: The inhibitory effect of andrographolide sodium bisulphite (ASB) on jack bean urease (JBU) and Helicobacter pylori urease (HPU) was performed to elucidate the inhibitory potency, kinetics and mechanism of inhibition in 20 mM phosphate buffer, pH 7.0, 2 mM EDTA, 25 °C. METHODS: The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of ASB was characterized with IC50 values. Lineweaver-Burk and Dixon plots for JBU inhibition of ASB was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni2+ binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. RESULTS: The IC50 of ASB against JBU and HPU was 3.28±0.13 mM and 3.17±0.34 mM, respectively. The inhibition proved to be competitive and concentration- dependent in a slow-binding progress. The rapid formation of initial ASB-JBU complex with an inhibition constant of Ki=2.86×10(-3) mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.33×10(-4) mM. The protective experiment proved that the urease active site is involved in the binding of ASB. Thiol reagents (L-cysteine and dithiothreithol) strongly protect the enzyme from the loss of enzymatic activity, while boric acid and fluoride show weaker protection, indicating that the active-site sulfhydryl group of JBU was potentially involved in the blocking process. Moreover, inhibition of ASB proved to be reversible since ASB-inactivated JBU could be reactivated by dithiothreitol application. Molecular docking assay suggested that ASB made contacts with the important sulfhydryl group Cys-592 residue and restricted the mobility of the active-site flap. CONCLUSIONS: ASB was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for the treatment of urease-related diseases.

Risk Factors of Tuberculosis Destroyed Lung in Patients with Pulmonary Tuberculosis and Structural Lung Diseases: A Retrospective Observational Study.

Background: Tuberculosis destroyed lung constitutes a significant worldwide public health challenge, little is known about its associated risk factors and prognosis. Our study aimed to identify the risk factors of tuberculosis destroyed lung among pulmonary tuberculosis and structural lung diseases. Methods: Between January 2019 and December 2021, a case-control study was conducted at the Third People's Hospital of Shenzhen in China. We collected the clinical data among patients with pulmonary tuberculosis and structural lung diseases. Cases were defined as patients with tuberculosis destroyed lung. Controls were not diagnosed with the tuberculosis destroyed lung. A binary logistic regression was performed. Results: In our study, a total of 341 patients met the inclusion criteria, including 182 cases and 159 controls. We found that age ranges of 46-60 years (aOR: 4.879; 95% CI: 2.338-10.180), >60 years (aOR: 3.384; 95% CI: 1.481-7.735); history of TB treatment (aOR: 2.729; 95% CI: 1.606-4.638); malnutrition (aOR: 5.126; 95% CI: 1.359-19.335); respiratory failure (aOR: 5.080; 95% CI: 1.491-17.306); and bronchiarctia (aOR: 3.499; 95% CI: 1.330-9.209) were the independent risk factors for tuberculosis destroyed lung. Conversely, having a normal (aOR: 0.207; 95% CI: 0.116-0.371) or overweight BMI (aOR: 0.259; 95% CI: 0.090-0.747) emerged as a protective factor against tuberculosis destroyed lung. Conclusion: This study indicated that tuberculosis destroyed lung is a common condition among patients with pulmonary tuberculosis and structural lung diseases. The independent risk factors for tuberculosis destroyed lung were identified as being within the age groups of 46-60 and over 60 years, having a previous history of TB treatment, malnutrition, respiratory failure, and bronchiarctia. It is essential to closely monitor patients possessing these risk factors to prevent the progression towards tuberculosis destroyed lung.

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen-thawed embryo transfer cycles.

OBJECTIVE: To compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. MATERIALS AND METHODS: This was a retrospective cohort study on patients undergoing polypectomy who underwent frozen-thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. RESULTS: There were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046-2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). CONCLUSION: GnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

A natural small molecule aspidosperma-type alkaloid, hecubine, as a new TREM2 activator for alleviating lipopolysaccharide-induced neuroinflammation in vitro and in vivo.

Neuroinflammation and oxidative stress play a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease. The triggering receptor expressed on myeloid cells 2 (TREM2), highly expressed by microglia in the central nervous system (CNS), can modulate neuroinflammatory responses. Currently, there are no approved drugs specifically targeting TREM2 for CNS diseases. Aspidosperma alkaloids have shown potential as anti-inflammatory and neuroprotective agents. This study aimed to elucidate the potential therapeutic effect of Hecubine, a natural aspidosperma-type alkaloid, as a TREM2 activator in lipopolysaccharide (LPS)-stimulated neuroinflammation in in vitro and in vivo models. In this study, molecular docking and cellular thermal shift assay (CTSA) were employed to investigate the interaction between Hecubine and TREM2. Enzyme-linked immunosorbent assay (ELISA), quantitative PCR, immunofluorescence, Western blotting, and shRNA gene knockdown were used to assess the anti-neuroinflammatory and antioxidant effects of Hecubine in microglial cells and zebrafish. Our results revealed that Hecubine directly interacted with TREM2, leading to its activation. Knockdown of TREM2 mRNA expression significantly abolished the anti-inflammatory and antioxidant effects of Hecubine on LPS-stimulated proinflammatory mediators (NO, TNF-α, IL-6, and IL-1ß) and oxidative stress in microglia cells. Furthermore, Hecubine upregulated Nrf2 expression levels while downregulating TLR4 signaling expression levels both in vivo and in vitro. Silencing TREM2 upregulated TLR4 and downregulated Nrf2 signaling pathways, mimicking the effect of Hecubine, further supporting TREM2 as the drug target by which Hecubine inhibits neuroinflammation. In conclusion, this is the first study to identify a small molecule, namely Hecubine directly targeting TREM2 to mediate anti-neuroinflammation and anti-oxidative effects, which serves as a potential therapeutic agent for the treatment of neural inflammation-associated CNS diseases.