A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Association between Red Blood Cell Distribution Width and In-Hospital Mortality among Congestive Heart Failure Patients with Diabetes among Patients in the Intensive Care Unit: A Retrospective Cohort Study.

Background: Elevated red blood cell distribution width (RDW) levels are strongly associated with an increased risk of mortality in patients with congestive heart failure (CHF). Additionally, heart failure has been closely linked to diabetes. Nevertheless, the relationship between RDW and in-hospital mortality in the intensive care unit (ICU) among patients with both congestive heart failure (CHF) and diabetes mellitus (DM) remains uncertain. Methods: This retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, a comprehensive critical care repository. RDW was assessed as both continuous and categorical variables. The primary outcome of the study was in-hospital mortality at the time of hospital discharge. We examined the association between RDW on ICU admission and in-hospital mortality using multivariable logistic regression models, restricted cubic spline analysis, and subgroup analysis. Results: The cohort consisted of 7,063 patients with both DM and CHF (3,135 females and 3,928 males). After adjusting for potential confounders, we found an association between a 9% increase in mortality rate and a 1 g/L increase in RDW level (OR = 1.09; 95% CI, 1.05∼1.13), which was associated with 11 and 58% increases in mortality rates in Q2 (OR = 1.11, 95% CI: 0.87∼1.43) and Q3 (OR = 1.58, 95% CI: 1.22∼2.04), respectively, compared with that in Q1. Moreover, we observed a significant linear association between RDW and in-hospital mortality, along with strong stratified analyses to support the findings. Conclusions: Our findings establish a positive association between RDW and in-hospital mortality in patients with DM and CHF.

Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction.

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10mg QD) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (Statin: n=8, 76±6 yr; Placebo: n=8, 68±9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-Minute Walk Test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under-the-curve (LBFAUC), increased following the statin intervention (pre: 60 ± 68 mL; post: 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group (P=0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre: 0.68 ± 0.10; post: 0.51 ± 0.11; P < 0.01), while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.

CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Preoperative camrelizumab combined with chemotherapy for borderline resectable ESCC: A single-arm, prospective, phase 2 study.

BACKGROUND: We investigated the safety and efficacy of preoperative camrelizumab combined with chemotherapy for treating thoracic borderline resectable esophageal squamous cell carcinoma (Br-ESCC) (ChiCTR2200056728). METHODS: Patients with thoracic Br-ESCC received intravenous camrelizumab plus chemotherapy and underwent esophagectomy. The primary endpoint was the pathologic complete response (pCR) rate. We introduced computed tomography and endoscopic examination into the diagnostic criteria to increase its reproducibility. Additionally, we defined a new resection status, Rbr+/-, for Br-ESCC. FINDINGS: Thirty-one patients with Br-ESCC were ultimately enrolled in this study. Overall, 71.0% (22/31) of the patients underwent esophagectomy. R0 resection was achieved in 81.8% of patients (18/22). pCR and major pathological response were observed in 40.9% (9/22) and 63.6% (14/22) of the resected patients, respectively. Eighteen R0 resection patients were redefined according to our Rbr definition; 61.1% (11/18) were classified as Rbr+ resection, and 38.9% (7/18) were classified as Rbr- resection. With a median postoperative follow-up of 17.9 months, 4 patients out of 11 who underwent Rbr+ resection experienced local recurrence (2 of whom achieved pCR). However, no patients (0/7) who underwent Rbr- resection experienced local recurrence. CONCLUSIONS: Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for Br-ESCC. R0 resection was achieved in 81.8% of patients, and a pCR was observed in 40.9% of resected patients. Even after complete excision, Rbr+ resection leads to a higher rate of local recurrence in patients with Br-ESCC. FUNDING: This study was supported by the Key Scientific Research Projects of the Institutions of Higher Learning in Henan Province (no. 21A320032).

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.

Tuning the Inter-Metal Interaction between Ni and Fe Atoms in Dual-Atom Catalysts to Boost CO2 Electroreduction.

Dual-atom catalysts (DACs) are promising for applications in electrochemical CO2 reduction due to the enhanced flexibility of the catalytic sites and the synergistic effect between dual atoms. However, precisely controlling the atomic distance and identifying the dual-atom configuration of DACs to optimize the catalytic performance remains a challenge. Here, the Ni and Fe atomic pairs were constructed on nitrogen-doped carbon support in three different configurations: NiFe-isolate, NiFe-N bridge, and NiFe bonding. It was found that the NiFe-N bridge catalyst with NiN4 and FeN4 sharing two N atoms exhibited superior CO2 reduction activity and promising stability when compared to the NiFe-isolate and NiFe-bonding catalysts. A series of characterizations and density functional theory calculations suggested that the N-bridged NiFe sites with an appropriate distance between Ni and Fe atoms can exert a more pronounced synergy. It not only regulated the suitable adsorption strength for the *COOH intermediate but also promoted the desorption of *CO, thus accelerating the CO2 electroreduction to CO. This work provides an important implication for the enhancement of catalysis by the tailoring of the coordination structure of DACs, with the identification of distance effect between neighboring dual atoms.

Preoperative administration of camrelizumab combined with chemotherapy for borderline resectable esophageal squamous cell carcinoma (BRES-1): study protocol of a single-arm, open-label, phase II study.

Background: The prognosis and first-line treatment response of patients with borderline resectable esophageal squamous cell carcinoma (ESCC) are unsatisfactory. We are conducting the borderline resectable esophageal squamous (BRES-1) study to evaluate the safety and efficacy of camrelizumab combined with chemotherapy in patients with borderline resectable ESCC. Methods: A total of 30 patients with borderline resectable ESCC will be enrolled in the BRES-1 study. These patients will undergo three stages of treatment: neoadjuvant therapy, surgery, and adjuvant therapy. Preoperative therapies will include camrelizumab, cisplatin, and nab-paclitaxel. Preoperative therapies will include camrelizumab, which will be given every 3 weeks for 6 weeks at a dose of 200 mg (baseline weight <50 kg, 3 mg/kg), nab-paclitaxel (130 mg/m2 on days 1 and 8 of one period with 21 days, a total of two cycles), and cisplatin (75 mg/m2 on day 1 of one period with 21 days, a total of two cycles). Patients will undergo esophagectomy 3-6 weeks after completing the neoadjuvant treatment. Three weeks after surgery, camrelizumab combined with chemotherapy will continue to be used for two cycles of maintenance therapy. Then, only camrelizumab will be administered for an entire year. The primary endpoint of this study will be pathological complete response (pCR). Discussion: The BRES-1 trial will evaluate the efficacy and safety of camrelizumab combined with chemotherapy for patients with borderline resectable ESCC. Translational research will explore perioperative complications and drug-related adverse events (AEs). Trial Registration: ChiCTR, ChiCTR2200056728. Registered 11 February 2022. https://www.chictr.org.cn/index.aspx.

Short-term outcomes of three- and two-field lymphadenectomy with minimally invasive esophagectomy for esophageal cancer: a propensity score-matching analysis.

Background: Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL. Methods: There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay. Results: There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 vs. 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 vs. 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group. Conclusions: Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging.

(+)-Catechin attenuates CCI-induced neuropathic pain in male rats by promoting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome.

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1ß. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.

Correlation of time trends of air pollutants, greenspaces and tracheal, bronchus and lung cancer incidence and mortality among the adults in United States.

Background: Tracheal, Bronchus, and Lung (TBL) cancer continues to represent the majority of cancer-related incidence and mortality in United States (U.S.). While air pollutants are considered essential risk factors, both global and national average concentrations of major harmful air pollutants have significantly decreased over the decades. Green space may have a beneficial effect on human health. Methods: We obtained data on national and state-level burden of TBL cancer, the annual average concentration of main air pollutants, and levels of green spaces in 2007, 2013, and 2019. According to generalized estimating equation (GEE), we examine the associations among incidence and mortality of TBL cancer, air pollutants, and greenspaces, represented by the Normalized Difference Vegetation Index (NDVI) in different age groups with models adjusted with meteorological, and socio-demographic. We observed additional effects of the interaction between the NDVI, Ozone, PM2.5, and other factors, which helped us to interpret and understand our results. Also, we collated states that witnessed net increments in forest coverage and conducted the same analysis separately. Results: In our analysis, the majority of associations between NDVI and air pollutants with TBL cancer remained significantly positive, particularly noticeable among individuals aged 20 to 54. However, our findings did not explore air pollution as a potential mediator between greenspace exposure and TBL cancer. While the associations of PM2.5 with TBL cancer remained positive, the other four pollutants showed positive but statistically insignificant associations. Our interaction analysis yielded that there were positive associations between NDVI and ozone, PM2.5, and tobacco use. Max NDVI acts as a protective factor along with high HDI. Additionally, PM2.5 and HDI also showed a negative association. In 18 states with more forest, NDVI acts as a protective factor along with higher health care coverage, better health status, and participation in physical activities. Conclusion: In the state-level of U.S., the effects of total greenspace with TBL cancer are mixed and could be modified by various socio-economic factors. PM2.5 has a direct correlation with TBL cancer and the effects can be influenced by underlying socioeconomic conditions.

Mechanism of Autocatalytic Reduction of CO2 over MgCO3 to High Value-Added Chemicals: A DFT & AIMD Study.

Calcination of MgCO3 is an important industrial reaction, but it causes significant and unfavorable CO2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*→ COOH*trans→ COOH*cis→ CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O-CH2 → sur-O-CH3 → sur-O + CH4*).

Knocking out isopropylmalate synthase simultaneously improves grain appearance and nutritional quality in rice.

Grain appearance and nutritional quality are critical traits for rice marketing. However, how to simultaneously improve grain appearance (slender grain and low chalkiness) and nutritional quality (improved protein and amino acid contents) in rice remains a major challenge. Here, we show that knocking out rice isopropylmalate synthase genes OsIPMS1 and OsIPMS2 can improve both grain appearance and nutritional quality. We find that OsIPMS1 directly interacts with OsIPMS2 to form heterodimers. Meanwhile, we observe that OsIPMS1 and OsIPMS2 influence the expression of genes previously reported to be involved in the determination of grain size and nutritional quality in the developing panicles and grains. Furthermore, we show that Osipms1/2 double mutants exhibit significantly improved grain appearance and nutritional quality in polished rice in both the japonica (Wuyungeng 23) and indica (Huanghuazhan) varieties. Our findings indicate that OsIPMS is a useful target gene for breeding of rice varieties appealing for marketing and with health-benefiting properties.

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

Non-classical Deactivation Mechanism in a Supported Intermetallic Catalyst for Propane Dehydrogenation.

Platinum-based supported intermetallic alloys (IMAs) demonstrate exceptional performance in catalytic propane dehydrogenation (PDH) primarily because of their remarkable resistance to coke formation. However, these IMAs still encounter a significant hurdle in the form of catalyst deactivation. Understanding the complex deactivation mechanism of supported IMAs, which goes beyond conventional coke deposition, requires meticulous microscopic structural elucidation. In this study, we unravel a nonclassical deactivation mechanism over a PtZn/γ-Al2O3 PDH catalyst, dictated by the PtZn to Pt3Zn nanophase transformation accompanied with dezincification. The physical origin lies in the metal support interaction (MSI) that enables strong chemical bonding between hydroxyl groups on the support and Zn sites on the PtZn phase to selectively remove Zn species followed by the reconstruction towards Pt3Zn phase. Building on these insights, we have devised a solution to circumvent the deactivation by passivating the MSI through surface modification of γ-Al2O3 support. By exchanging protons of hydroxyl groups with potassium ions (K) on the γ-Al2O3 support, such a strategy significantly minimizes the dezincification of PtZn IMA via diminished metal-support bonding, which dramatically reduces the deactivation rate from 0.2044 to 0.0587 h-1.

Molecular Modification Strategies of Nitrilase for Its Potential Application in Agriculture.

Some feed source plants will produce secondary metabolites such as cyanogenic glycosides during metabolism, which will produce some poisonous nitrile compounds after hydrolysis and remain in plant tissues. The consumption of feed-source plants without proper treatment affect the health of the animals' bodies. Nitrilases can convert nitriles and have been used in industry as green biocatalysts. However, due to their bottleneck problems, their application in agriculture is still facing challenges. Acid-resistant nitrilase preparations, high-temperature resistance, antiprotease activity, strong activity, and strict reaction specificity urgently need to be developed. In this paper, the application potential of nitrilase in agriculture, especially in feed processing industry was explored, the source properties and catalytic mechanism of nitrilase were reviewed, and modification strategies for nitrilase application in agriculture were proposed to provide references for future research and application of nitrilase in agricultural and especially in the biological feed scene.

Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.

Regulated cell death (RCD) is a controlled form of cell death orchestrated by one or more cascading signaling pathways, making it amenable to pharmacological intervention. RCD subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis, facilitating development, and modulating immunity. Accumulating evidence has recently revealed that RCD evasion is frequently the primary cause of tumor survival. Several non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse, comparable to apoptosis. Moreover, they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic drugs. With an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines, a growing number of small-molecule compounds targeting single or multiple pathways have been discovered, providing novel strategies for current cancer therapy. In this review, we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines, mainly including autophagy-dependent cell death, ferroptosis, cuproptosis, disulfidptosis, necroptosis, pyroptosis, alkaliptosis, oxeiptosis, parthanatos, mitochondrial permeability transition (MPT)-driven necrosis, entotic cell death, NETotic cell death, lysosome-dependent cell death, and immunogenic cell death (ICD). Furthermore, we focused on discussing the pharmacological regulatory mechanisms of related small-molecule compounds. In brief, these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines, ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.

Effect of different endometrial preparation methods on pregnancy outcome of FET in women with a normal menstrual cycle.

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

Coronary Artery Calcium Score-Weighted Clinical Likelihood Model Performance in Patients with Stable Chest Pain and Coronary Artery Calcium Scores of Zero.

Background: For individuals with persistent stable chest pain (SCP) and a coronary artery calcium score (CACS) of 0, it might be challenging to establish the best risk assessment method for determining the individuals who will not benefit from further cardiovascular imaging testing (CIT). Thus, we investigated the CACS-weighted clinical likelihood (CACS-CL) model in SCP patients with a CACS of 0. Methods: Thus, to assess SCP, we originally enrolled 14,232 individuals for CACS and coronary computed tomography angiography (CCTA) scans between January 2016 and January 2018. Finally, patients with a CACS of 0 were included and followed up ​until January 2022. According to the established CACS-CL cutoffs of 15% and 5%, the associations between coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in risk groups were evaluated, alongside the net reclassification improvement (NRI). Results: Of the 6689 patients with a CACS of 0, the prevalence of CAD increased significantly (p < 0.0001) in patients with higher CACS-CL. However, there was no significant difference in the CAD distribution (p = 0.0637) between patients with CACS-CL < 5% and 5-15%. The association between the CACS-CL = 15%-determined risk groups and the occurrence of MACEs was stronger than for a CACS-CL = 5% (adjusted hazard ratio (HR): 7.24 (95% CI: 1.93-16.42) versus 3.68 (95% CI: 1.50-8.26)). Compared with the cutoff for CACS-CL = 5%, the NRI was 10.61% when using a cutoff for CACS-CL = 15%. Conclusions: Among patients with an SCP and CACS of 0, the CACS-CL model provided accurate predictions of CAD and MACEs. Compared to the cutoff for CACS-CL = 5%, the cutoff for CACS-CL = 15% seemed to be more effective and safer for deferring further CIT. Clinical Trial registration: NCT04691037.

Rationally designed Ru catalysts supported on TiN for highly efficient and stable hydrogen evolution in alkaline conditions.

Electrocatalysis holds the key to enhancing the efficiency and cost-effectiveness of water splitting devices, thereby contributing to the advancement of hydrogen as a clean, sustainable energy carrier. This study focuses on the rational design of Ru nanoparticle catalysts supported on TiN (Ru NPs/TiN) for the hydrogen evolution reaction in alkaline conditions. The as designed catalysts exhibit a high mass activity of 20 A mg-1Ru at an overpotential of 63 mV and long-term stability, surpassing the present benchmarks for commercial electrolyzers. Structural analysis highlights the effective modification of the Ru nanoparticle properties by the TiN substrate, while density functional theory calculations indicate strong adhesion of Ru particles to TiN substrates and advantageous modulation of hydrogen adsorption energies via particle-support interactions. Finally, we assemble an anion exchange membrane electrolyzer using the Ru NPs/TiN as the hydrogen evolution reaction catalyst, which operates at 5 A cm-2 for more than 1000 h with negligible degradation, exceeding the performance requirements for commercial electrolyzers. Our findings contribute to the design of efficient catalysts for water splitting by exploiting particle-support interactions.