Synthesis and clinical application of representative small-molecule dipeptidyl Peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus (T2DM).

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels, which can cause many diseases, including osteoporosis, fractures, arthritis, and foot complications. The inhibitors of dipeptidyl peptidase-4 (DPP-4), an enzyme involved in glucose metabolism regulation, are essential for managing Type 2 Diabetes Mellitus (T2DM). The inhibition of DPP-4 has become a promising treatment approach for T2DM because it can increase levels of active glucagon-like peptide-1 (GLP-1), leading to improved insulin secretion in response to glucose and reduced release of glucagon. The review commences by elucidating the role of DPP-4 in glucose homeostasis and its significance in T2DM pathophysiology. Furthermore, it presents the mechanism of action, preclinical pharmacodynamics, clinical efficacy, and toxicity profiles of small-molecule DPP-4 inhibitors across various clinical stages. This comprehensive review provides valuable insights into the synthesis and clinical application of DPP-4 inhibitors, serving as an invaluable resource for researchers, clinicians, and pharmaceutical professionals interested in diabetes therapeutics and drug development.

DDIT3 aggravates TMJOA cartilage degradation via Nrf2/HO-1/NLRP3-mediated autophagy.

OBJECTIVE: DNA damage-inducible transcript 3 (DDIT3), as a downstream transcription factor of endoplasmic reticulum (ER) stress, is reported to regulate chondrogenic differentiation under physiological and pathological state. However, the specific involvement of DDIT3 in the degradation of condylar cartilage of TMJOA is unclarified. DESIGN: The expression patterns of DDIT3 in condylar cartilage from monosodium iodoacetate (MIA)-induced TMJOA mice were examined to uncover the potential role of DDIT3 in TMJOA. The Ddit3 knockout (Ddit3-/-) mice and their wildtype littermates (Ddit3+/+) were used to clarify the effect of DDIT3 on cartilage degradation. Primary condylar chondrocytes and ATDC5 cells were applied to explore the mechanisms of DDIT3 on autophagy and extracellular matrix (ECM) degradation in chondrocytes. The autophagy inhibitor chloroquine (CQ) was used to determine the effect of DDIT3-inhibited autophagy in vivo. RESULTS: DDIT3 were highly expressed in condylar cartilage from TMJOA mice. Ddit3 knockout alleviated condylar cartilage degradation and subchondral bone loss, compared with their wildtype littermates. In vitro study demonstrated that DDIT3 exacerbated ECM degradation in chondrocytes induced by TNF-α through inhibiting autophagy. The intraperitoneal injection of CQ further confirmed that Ddit3 knockout alleviated cartilage degradation in TMJOA through activating autophagy in vivo. CONCLUSIONS: Our findings identified the crucial role of DDIT3-inhibited autophagy in condylar cartilage degradation during the development of TMJOA.

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.

Status and influencing factors of nurses' burnout: A cross-sectional study during COVID-19 regular prevention and control in Jiangsu Province, China.

Background: Chinese nurses working with immense stress may have issues with burnout during COVID-19 regular prevention and control. There were a few studies investigating status of burnout and associated factors among Chinese nurses. However, the relationships remained unclear. Objectives: To investigate status and associated factors of nurses' burnout during COVID-19 regular prevention and control. Methods: 784 nurses completed questionnaires including demographics, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, Impact of Event Scale-revised, Perceived Social Support Scale, Connor-Davidson Resilience Scale, General Self-efficacy Scale and Maslach Burnout Inventory. Results: 310 (39.5%), 393 (50.1%) and 576 (73.5%) of respondents were at high risk of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). The risk of EE, DP and reduced PA were moderate, high and high. Nurses with intermediate and senior professional rank and title and worked >40 h every week had lower scores in EE. Those worked in low-risk department reported lower scores in PA. Anxiety, post-traumatic stress disorder (PTSD), self-efficacy and social support were influencing factors of EE and DP, while social support and resilience were associated factors of PA. Conclusion: Chinese nurses' burnout during COVID-19 regular prevention and control was serious. Professional rank and title, working unit, weekly working hours, anxiety, PTSD, self-efficacy, social support and resilience were associated factors of burnout.

Experimental Study on Enhanced Methane Detection Using an MEMS-Pyroelectric Sensor Integrated with a Wavelet Algorithm.

An optical sensing approach that balances portability with cost efficiency has been designed for the reliable monitoring of fugitive methane (CH4) emissions. Employing a LiTaO3-based pyroelectric detector integrated with micro-electro-mechanical systems and a broad infrared source, the developed gas sensor adeptly measured CH4 concentrations with a low limit of detection of about 5.6 ppmv and showed rapid response times with t90 consistently under 3 s. Notably, the novelty of our method lies in its precise control and reduction of CH4 levels, enhanced by wavelet denoising. This technique, optimized through meticulous grid search, effectively mitigated noise interference noticeable at CH4 levels below 10 ppmv. Postdenoising, nonlinear regression analyses based on the modified Beer-Lambert equation returned R2 values of 0.985 and 0.982 for the training and validation sets, respectively. In conclusion, this gas sensor has been shown to be able to meet the requirements for early warning of CH4 leakage on the surface in various carbon capture, utilization, and storage projects such as enhanced oil or gas recovery projects using CO2 injection.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

[Applicability of H2FPEF and HFA-PEFF Scores in Chinese Patients Suffering From Heart Failure With Preserved Ejection Fraction and Heart Failure With Preserved Ejection Fraction Complicated With Atrial Fibrillation].

Objective To analyze the diagnostic values of H2FPEF and HFA-PEFF scores for heart failure with preserved ejection fraction (HFpEF) and HFpEF complicated with atrial fibrillation (HFpEF-AF) in Chinese patients and explore the related factors. Methods A cross-sectional study was conducted.A total of 835 consecutive HFpEF patients treated in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from 2009 to 2020 were selected and assigned to a HFpEF-AF group (n=267) and a HFpEF group (n=568) according to the presence of AF or not.HFA-PEFF and H2FPEF scores were used for retrospective diagnosis and the diagnostic consistency of the two scores was assessed.One hundred and thirty-six healthy volunteers with age and sex matching the patients during the same period were selected as healthy controls.The receiver operating characteristic (ROC) curves were established for H2FPEF and HFA-PEFF scores in diagnosing HFpEF-AF and HFpEF,on the basis of which the diagnostic performance of the two scores was evaluated. Results There was no difference in the HFA-PEFF score between the two groups (P=0.070).However,the HFpEF-AF group had higher mean H2FPEF score and higher proportion of patients with the score no less than 6 than the HFpEF group (P<0.001).According to the ROC curves,HFA-PEFF and H2FPEF scores demonstrated high performance in diagnosing all HFpEF patients,with the area under the curve (AUC) of 0.892 and 0.922 and the optimal cut-offs of 4 and 4,respectively.The HFA-PEFF score showed similar performance in diagnosing HFpEF and HFpEF-AF,with the AUC of 0.899 and 0.911,respectively.The H2FPEF score had higher performance in diagnosing HFpEF-AF (AUC of approximately 1.000) and low performance in diagnosing HFpEF (AUC of 0.885). Conclusions The HFA-PEFF score is applicable in the diagnosis of both HFpEF and HFpEF-AF.The H2FPEF score may underestimate HFpEF in Chinese patients,and its applicability in the Chinese patients with HFpEF alone remains to be investigated.

Independent effect of the triglyceride-glucose index on all-cause mortality in critically ill patients with chronic obstructive pulmonary disease and asthma: A retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index serves as a reliable proxy for insulin resistance (IR). IR has been linked to heightened incidence, prevalence, or severity of chronic obstructive pulmonary disease (COPD) and asthma. Prior research indicates that critically ill patients are prone to developing IR. Nevertheless, few studies have delved into the correlation between IR and all-cause mortality in critically ill patients with COPD and asthma. Therefore, the aim of this study is to explore the association between the TyG index and all-cause mortality in patients with COPD and asthma, with the goal of assessing the impact of IR on the prognosis of this patient population. METHODS: This is a retrospective study, and all data are from the Medical Information Mart for Intensive Care IV (MIMIC-IV) critical care database. This study included 684 ICU patients with COPD and asthma and divided them into quartiles based on TyG index levels. The primary outcomes of this study were all-cause mortality during follow-up, encompassing mortality at 30 days, 90 days, and 180 days. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality in critically ill patients with COPD and asthma. Restricted cubic spline analysis was used to assess potential nonlinear association between the TyG index and the primary outcome. RESULTS: A total of 684 patients (53.9% female) were included. The 90-days all-cause mortality rate and 180-days all-cause mortality were 11.7% and 12.3%, respectively. Kaplan-Meier analysis revealed a significant association between the TyG index and both 90-days all-cause mortality (log-rank p = .039) and 180-days all-cause mortality (log-rank p = .017). Cox proportional hazards analysis revealed a significant association between the TyG index and 90-days all-cause mortality in both the unadjusted model (HR, 1.30 [95% CI 1.08-1.57] p = .005) and the model adjusted for age, gender, and diabetes (HR, 1.38 [95% CI 1.15-1.67] p < .001). Similarly, the TyG index was associated with 180-days all-cause mortality in the unadjusted model (HR, 1.30 [95% CI 1.09-1.56] p = .004) and the model adjusted for age, sex, and diabetes (HR, 1.38 [95% CI 1.15-1.66] p < .001). The restricted cubic splines (RCS) regression model indicated a significant nonlinear association between the TyG index and both 90-days and 180-days all-cause mortality. Specifically, TyG index >4.8 was associated with an increased risk of mortality at both 90 days and 180 days. CONCLUSIONS: In summary, our results extend the utility of the TyG index to critically ill patients with COPD and asthma. Our study shows that the TyG index is a potential predictor of all-cause mortality in critically ill patients with COPD and asthma. In addition, in patients with a TyG index exceeding 4.8, there was a heightened risk of mortality. Measuring the TyG index may help with risk stratification and prognosis prediction in critically ill patients with COPD and asthma. Further prospective studies are needed to confirm our findings.

Rice quality prediction and assessment of pesticide residue changes during storage based on Quatformer.

Rice serves as a fundamental food staple for humans. Its production process, however, unavoidably exposes it to pesticides which may detrimentally impact its quality due to residues. Therefore, it is extremely necessary to monitor pesticide residues on rice during storage. In this research, the Quatformer model, which considers the effects of temperature and humidity on pesticide residues in rice grains, was utilized to forecast the amount of pesticide residues in rice grains during the storage process, and the predicted results were combined with actual observations to form a quality assessment index. By applying the K-Means algorithm, the quality of rice grains was graded and assessed. The findings indicated that the model had high prediction accuracy, and the MAE, MSE, MAPE, RMSE and SMAPE indexes were calculated to be 0.0112, 0.0814, 0.1057, 0.1055 and 0.0204, respectively. These findings provide valuable technical and theoretical support for planning storage conditions, enhancing pesticide residue decomposition, and monitoring rice quality during storage.

Rare retroperitoneal giant sacral schwannoma: A case report.

Schwannomas localized in the sacrum are relatively infrequent, accounting for 1-5% of all spinal axis schwannomas; they present with vague symptoms or are symptomless, so often grow to a considerable size before detection. Sacral schwannomas occasionally present with enormous dimensions, and these tumors are termed giant sacral schwannomas. However, their surgical removal is challenging owing to an abundant vascularity. The present study retrospectively analyzed the clinical and follow-up data of a patient with a giant sacral schwannoma. The patient experienced numbness in the left buttock and lower extremity, with radiating pain in the sole of the foot that had persisted for 3 years. A presacral mass was found by computed tomography examination 6 months after the stool had become thin. A tumor resection was performed using the anterior abdominal approach. A schwannoma was diagnosed by postoperative pathology. The postoperative course was uneventful, with the complete resolution of symptoms during the 21-month clinical follow-up. Overall, the present study reports the case of a giant sacral schwannoma with pelvic pain that was resected without complications and also discusses its successful management. Additionally, the study presents a systematic review of the literature. We consider that the surgical treatment of giant sacral schwannomas with piecemeal subtotal excision can achieve good outcomes, avoiding unnecessary neurological deficits.

Three Novel Cheiroid Hyphomycetes in Dictyocheirospora and Dictyosporium (Dictyosporiaceae) from Freshwater Habitats in Guangdong and Guizhou Provinces, China.

Over the past two decades, numerous novel species have been identified within Dictyosporiaceae, primarily in Dictyocheirospora and Dictyosporium. A recent monograph has revealed that these two genera exhibit a distinct preference for freshwater habitats, particularly in southern China. However, further investigation into the distribution and diversity of the two genera in Guangdong and Guizhou Provinces remains insufficient. In this study, we conducted an analysis of four intriguing cheiroid hyphomycetes collected from flowing rivers in these two regions. Through morphological and phylogenetic analyses incorporating combined LSU, SSU, ITS, and tef1-α sequence data, we have identified them as a novel species in Dictyocheirospora (Dictyoc. submersa sp. nov.), two novel species in Dictyosporium (Dictyos. guangdongense sp. nov. and Dictyos. variabilisporum sp. nov.), and one previously documented species (Dictyos. digitatum). Specifically, the identification of Dictyos. guangdongense is primarily based on its distinct morphology, characterized by complanate, cheiroid, and brown to dark brown conidia, with a hyaline, short, and atrophied appendage arising from the apical cell of the outer row. In addition, the morphological distinctions between Dictyocheirospora and Dictyosporium are further clarified based on our new data. This study also highlights a few phylogenetic matters regarding Dictyosporiaceae.

WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

E93 is indispensable for reproduction in ametabolous and hemimetabolous insects.

Ecdysone-induced protein 93 (E93), known as the "adult-specifier" transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. While E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discovered that in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNAs are broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we revealed that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

[Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome].

OBJECTIVE: To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) transformed from myelodysplastic syndrome (MDS). METHODS: The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed. The demographic data and laboratory parameters, cytogenetic karyotypes, target genes of AML detected by next generation sequence, risk stratification, treatment regimen, therapeutic efficacy and survival outcome were documented. Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy. The effects of clinical parameters, risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis. RESULTS: The median overall survival (OS) of the AML-MRC patients was 4.5 months, the 1-year OS rate was 28.3%, and the complete remission (CR) rate after treatment was 33.3%. The univariate analysis showed that age≥60 years, leukocytosis, severe thrombocytopenia, poor-risk group and only accepted hypomethylating agents(HMAs) or supportive therapy were the risk factors affecting OS. COX multivariate analysis showed that thrombocytopenia ( HR=4.46), HMAs therapy (compared to transplantation, HR=10.47), supportive therapy (compared to transplantation, HR=25.80) and poor-risk group (compared to medium-risk group, HR=13.86) were independent hazard factors for median OS of patients with AML-MRC. The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age≥60 years, thrombocytopenia, time of transformation from MDS to AML (TTA)≥3 months, fibrinogen-albumin ratio index (FARI)≥0.07, CONUT score≥5, poor-risk group and supportive therapy. Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age≥60 years ( HR=11.23), thrombocytopenia ( HR=8.71), FARI≥0.07 ( HR=5.19) and poor-risk group ( HR=14.00). The risk factors affecting CR of AML-MRC patients in univariate analysis were age≥60 years, thrombocytopenia, FARI≥0.1, CONUT score≥5, poor-risk group and supportive therapy, while binary logistic regression analysis showed that age≥60 years( HR=7.35), CONUT score≥5 ( HR=9.60), thrombocytopenia ( HR=12.05) and poor-risk group ( HR=32.5) were independent risk factors affecting CR of the patients. CONCLUSION: The OS of AML-MRC patients is poor, old age(≥60 years old), supportive therapy, HMA therapy, poor-risk, thrombocytopenia, FARI≥0.07 and CONUT score≥5 may be associated with poor prognosis.

A single-chain antibody construct with specificity of a natural IgM antibody reduces hepatic ischemia reperfusion injury in mice.

Natural immunoglobulin M (IgM) antibodies have been shown to recognize post-ischemic neoepitopes following reperfusion of tissues and to activate complement. Specifically, IgM antibodies and complement have been shown to drive hepatic ischemia reperfusion injury (IRI). Herein, we investigate the therapeutic effect of C2 scFv (single-chain antibody construct with specificity of a natural IgM antibody) on hepatic IRI in C57BL/6 mice. Compared with PBS-treated mice, C2 scFv-treated mice displayed almost no necrotic areas, significant reduction in serum ALT, AST and LDH levels, and significantly reduced in the number of TUNEL positive cells. Moreover, C2 scFv-treated mice exhibited a notable reduction in inflammatory cells after hepatic IRI than PBS-treated mice. The serum IL-6, IL-1ß, TNF-α and MPC-1 levels were also severely suppressed by C2 scFv. Interestingly, C2 scFv reconstituted hepatic inflammation and IRI in Rag1-/- mice. We found that C2 scFv promoted hepatic cell death and increased inflammatory cytokines and infiltration of inflammatory cells after hepatic IRI in Rag1-/- mice. In addition, IgM and complement 3d (C3d) were deposited in WT mice and in Rag1-/- mice reconstituted with C2 scFv, indicating that C2 scFv can affect IgM binding and complement activation and reconstitute hepatic IRI. C3d expression was significantly lower in C57BL/6 mice treated with C2 scFv compared to PBS, indicating that excessive exogenous C2 scFv inhibited complement activation. These data suggest that C2 scFv alleviates hepatic IRI by blocking complement activation, and treatment with C2 scFv may be a promising therapy for hepatic IRI.

Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits.

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

The influence of two distinct surface modification techniques on the clinical efficacy of titanium implants: A systematic review and meta-analysis.

PURPOSE: To compare the effectiveness of anodized and sandblasted large-grit acid-etched surface modification implants in clinical applications. METHODS: This systematic review has been registered at PROSPERO (CRD42023423656). A systematic search was performed using seven databases. The meta-analysis was performed using the RevMan 5.4 program and Stata 17.0 software. An analysis of the risk of bias in the included studies was conducted using the Cochrane Handbook for Systematic Reviews of Interventions and the Newcastle-Ottawa scale. RESULTS: A comprehensive analysis of 16 studies, which collectively encompassed a total of 2768 implants, was finished. Following a five years follow-up, the meta-analysis showed that the cumulative survival rate of implants was lower in the anodized group compared to the sandblasted large-grit acid-etched group (RR, 3.47; 95 % confidence interval [CI], 1.23 to 9.81; P = 0.02). Furthermore, the anodized group and the sandblasted large-grit acid-etched group had similar marginal bone loss over the one to three years follow-up period. However, it was observed that the marginal bone loss increased at the five years follow-up period in the anodized group in comparison to the sandblasted large-grit acid-etched group (SMD, 2.98; 95 % CI, 0.91 to 5.06; P = 0.005). In terms of biological complications, plaque index, bleeding on probing, and probing pocket depth, we found no statistically significant differences between the anodized and sandblasted large-grit acid-etched group. CONCLUSIONS: The sandblasted large-grit acid-etched group exhibited higher implants cumulative survival rate and less marginal bone loss compared to the anodized group. Moreover, both groups demonstrated similar incidences of biological complications, plaque index, bleeding on probing, and probing pocket depth, suggesting overall equivalence in these aspects.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Discovery of palmatine derivatives as potent neuroprotective agents.

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.