Causal association of immune effector proteins with sepsis: A Mendelian randomization study.

Sepsis is an infection-induced systemic inflammatory response syndrome. Immune regulation plays a crucial role in sepsis. We looked into the link between immune effector-related proteins and sepsis in this study by using both univariate and multivariate Mendelian randomization (MR) analyses. We accessed and collected data from the Integrative Epidemiology Unit's Open About Sepsis genome-wide association study database. The 6 immune effector-associated proteins each contained 10,534,735 single-nucleotide polymorphisms from 3301 samples. Using the weighted median, MR-Egger, simplex, inverse-variance weighting, and weighted mode methods, univariate MR then investigated the link between complement factor H-related protein-5 (CFHR5), Fc epsilon receptor II (FCER2), granzyme B (GZMB), major histocompatibility complex, class II, DQ alpha (HLA-DQA2), mannose-binding lectin 2 (MBL2), or myeloperoxidase (MPO) and sepsis. In the inverse-variance weighted results, the P values of all 6 immune effector-related proteins were <0.05, suggesting a possible causal relationship between them and sepsis. MBL2 (odds ratio [OR] = 1.046) was a risk factor for sepsis, while the other proteins (FCER2: OR = 0.922; GZMB: OR = 0.908; CFHR5: OR = 0.858; HLA-DQA2: OR = 0.896; MPO: OR = 0.875) were safety factors. By revealing a causal link between sepsis and CFHR5, FCER2, GZMB, HLA-DQA2, MBL2, or MPO, our study offers an essential resource for additional investigations on the subject.

Shopping around: Comparing Cd(II) sorption performance of disparate functional groups-modified microcrystalline cellulose composites.

The structure-function relationship of functionalized microcrystalline cellulose (MCC) composites as adsorbents remains unclear. Herein, the orange peel-derived MCC (i.e., OP-OH-H-25) was treated by different functional agents to prepare adsorbents for cadmium (Cd(II)) removal. Mercaptoacetic acid and orthophosphoric acid did not apparently impact MCC's surface site types and contents. Alternatively, they efficiently purified OP-OH-H-25 and generated OP-OH-SH and OP-OH-P samples with increased cellulose amounts. In contrast, the glycine modification produced OP-OH-NH2 with fewer sulfhydryl/carboxyl functional groups and more amide/amino sites. The pH-dependent Cd(II) removal trends by the MCC-related materials showed three successive stages with disparate sorption modes. The Cd(II) sorption kinetics processes on OP-OH-SH, OP-OH-P, and OP-OH-NH2 reached equilibrium after 0.25 h, faster than 0.5 h on OP-OH-H-25. The maximum Cd(II) sorption capacities of MCC-related adsorbents were OP-OH-P (151.81 mg/g) > OP-OH-SH (150.80 mg/g) > OP-OH-H-25 (124.90 mg/g) > > OP-OH-NH2 (55.23 mg/g). OP-OH-P exhibited the strongest Cd(II) sorption ability under the interference of mixed aquatic components. The intrinsic Cd(II) sorption mechanisms were identified as inner-sphere complexation and cation-π bond interaction. Overall, the select priority of modifying agents is orthophosphoric acid > mercaptoacetic acid > > glycine when preparing functionalized MCC adsorbents for purifying Cd(II)-polluted water systems.

The Risk of Deep Vein Thrombosis and Optimal Timing of Breast Cancer Surgery After COVID-19 Infection.

PURPOSE: The aim of this study was to assess the risk of postoperative deep vein thrombosis (DVT) in breast cancer patients with coronavirus disease 2019 (COVID-19) to determine the optimal timing for surgery in the era of "post COVID-19 pandemic." METHODS: This prospective study included breast cancer patients who contracted COVID-19 and underwent surgery from December 20th, 2022, to March 20th, 2023 (n = 577). A control group comprised patients who underwent surgery from May 1st, 2019, to October 1st, 2019 (n = 327) and had not contracted COVID-19 prior to surgery. Patients were categorized based on the timing of their surgery relative to their COVID-19 infection. Data were analyzed using logistic regression. RESULTS: Patients with COVID-19 had a higher incidence of postoperative DVT compared to those without COVID-19 (3.64% vs. 1.21%). Multivariable logistic regression analysis indicated that the timing of surgery was significantly associated with the risk of DVT (odds ratio [OR], 2.795; 95% confidence interval [CI], 0.692-11.278; p = 0.024). Patients who underwent surgery within two weeks of COVID-19 infection experienced the highest DVT rates (OR, 10.556; 95% CI, 1.095-303.313; p = 0.003). However, the incidence decreased to 2.85% when surgery was delayed until two weeks or more after infection. The median follow-up period was 10 months, all patients with DVT after surgery were recovered without serious complications or death. There were no adverse effects on subsequent anti-tumor therapy. CONCLUSION: Caution is advised when performing breast cancer surgery within two weeks after a COVID-19 infection. Although the risk of DVT remains somewhat elevated even after two weeks, surgery can be considered safe given the urgency of treatment, favorable complication outcomes, and lack of impact on subsequent adjuvant therapy.

Optimal management of breast cancer with physical exam negative/radiological abnormal axilla.

For breast cancer patients with physical exam node negative but radiological finding node abnormal (cN0/rNa), the NCCN and ASCO guidelines recommend sentinel lymph node biopsy (SLNB) as the first-line axillary staging. However, patients who undergo surgery firstly may be upstaged to pathological II-III status, and these patients happen to be the adaptive population of neoadjuvant therapy (NAT). There is no consensus on the optimal management of cN0/rNa patients. The aim is to explore the optimal management strategy of these patients. We performed a retrospective real-world study of 1414 cN0/rNa patients from June 2014 to October 2022. There were 1003 patients underwent surgery first and 411 patients underwent surgery after NAT. We analyzed the real-world conditions of these patients, compared axilla tumor burden between these two groups. In addition, we compared benefit ratio of axillary surgery and regional nodal irradiation (RNI) de-escalation under the two strategies. Among 1003 patients underwent surgery first, the positive and negative rates of fine needle aspiration (FNA) were 18.5% and 81.5%, respectively. There were 66.1% had ≤ 2 lymph nodes+. There were 40.8% of FNA+ patients could be exempted from ALND underwent surgery first. In 411 patients underwent surgery after NAT, the FNA positive and negative rates were 60.8% and 49.2%, respectively. There were 54.4% of FNA+ patients achieved axilla pathologic complete response (apCR) and could omit ALND after NAT. The apCR was 67.3% in HER2+/TNBC subtypes. According to the NSABP-B51 trial, there were 0 and 54.4% of FNA+ patients could omit RNI among surgery first and after NAT, respectively. Among 1-2 sentinel lymph node (SLN)-positive patients underwent surgery first, with a median follow-up 49 months, there was no difference of survival benefit between SLNB-only and SLNB-ALND. Compared with 1-2 SLN+ patients without RNI, RNI could bring better invasive disease-free survival (97.38% vs. 89.36%, P = 0.046) and breast cancer special survival (100% vs. 94.68%, P = 0.020). It is safe to perform SLNB omitting ALND when detected 1-2 positive SLNs in cN0/rNa patients. Patients with HER2+/TNBC subtypes underwent surgery after NAT had more chance to benefit from dual de-escalation, including axillary surgery and RNI de-escalation.

InDel mutations within the bovine PER2 gene are significantly associated with reproductive traits.

Functioning as a key regulator of circadian rhythms, the PER2 gene exerts a substantial impact on the reproductive traits of animals. However, the effect of the PER2 gene on ovarian development remains unclear. In order to examine the relationship between bovine reproductive trait and the PER2 gene, a total of 901 ovarian samples were collected, categorized into different oestrus cycles (proestrus, oestrus, post-oestrus, anoestrous), and subjected to analysis for two potential insertion/deletions (InDels) in the PER2 gene. Through agarose gel electrophoresis and DNA sequencing, two polymorphic deletion mutations (P2-D5-bp, P3-D13-bp) were identified. Furthermore, a significant association between mature follicle diameter and P2-D5-bp was found (P < 0.05). Additionally, several significant correlations with ovarian length, width, height, and white body diameter were found for P3-D13-bp (P < 0.05). These findings suggested that the bovine PER2 gene plays an important role in above-mentioned reproductive traits, offering new avenues for improving cow fertility through marker-assisted selection (MAS).

JAK2 inhibitor protects the septic heart through enhancing mitophagy in cardiomyocytes.

Sepsis-induced myocardial dysfunction (SIMD) is a severe complication in sepsis, manifested as myocardial systolic dysfunction, which is associated with poor prognosis and higher mortality. Mitophagy, a self-protective mechanism maintaining cellular homeostasis, plays an indispensable role in cardioprotection. This study aimed to unveil the cardioprotective effects of Baricitinib on LPS-induced myocardial dysfunction and its effect on mitophagy. Herein, we demonstrated that LPS induced severe myocardial dysfunction and initiated mitophagy in septic mice hearts. Despite the initiation of mitophagy, a significant number of apoptotic cells and damaged mitochondria persisted in the myocardium, and myocardial energy metabolism remained impaired, indicating that the limited mitophagy was insufficient to mitigate LPS-induced damage. The JAK2-AKT-mTOR signaling pathway is activated in LPS-induced cardiomyocytes and in the hearts of septic mice. Baricitinib administration remarkably improved cardiac function, suppressed systemic inflammatory response, attenuated histopathological changes, inhibited cardiac cell apoptosis and alleviated myocardial damage in septic mice. Furthermore, Baricitinib treatment significantly enhanced PINK1-Parkin-mediated mitophagy, increased autophagosomes, decreased impaired mitochondria, and restored myocardial energy metabolism. Mechanically, the limited mitophagy in septic myocardium was associated with increased p-ULK1 (Ser757), which was regulated by p-mTOR. Baricitinib reduced p-ULK1 (Ser757) and enhanced mitophagy by inhibiting the JAK2-AKT-mTOR signaling pathway. Inhibition of mitophagy with Mdivi-1 reversed the cardiac protective and anti-inflammatory effects of Baricitinib in septic mice. These findings suggest that Baricitinib attenuates SIMD by enhancing mitophagy in cardiomyocytes via the JAK2-AKT-mTOR signaling pathway, providing a novel mechanistic and therapeutic insight into the SIMD.

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistance, including on-target mechanisms and off-target mechanisms, as well as changes in the tumor histology and tumor microenvironment (intrinsic mechanisms). Additionally, we summarized current therapeutic approaches aiming at circumventing TKI resistance, including the development of next-generation TKIs and combination therapies. We also discussed emerging strategies such as the use of dual-targeted antibodies and PROteolysis Targeting Chimeras. Furthermore, we explored future directions in TKI-targeted therapy, including the methods for detecting and monitoring drug resistance during treatment, identification of novel targets, exploration of dual-acting kinase inhibitors, application of nanotechnologies in targeted therapy, and so on. Overall, this review provides a comprehensive overview of the challenges and opportunities in TKI-targeted therapy, aiming to advance our understanding of resistance mechanisms and guide the development of more effective therapeutic approaches in cancer treatment.

The feasibility of targeted axillary dissection for breast cancer axillary surgery de-escalation after neoadjuvant therapy: A prospective cohort study.

PURPOSE: Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. METHODS: From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). RESULTS: The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3 mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). CONCLUSION: Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

Associations among dietary 1-carbon metabolism nutrients, genetic risk, and Alzheimer disease: a prospective cohort study.

BACKGROUND: The associations between 1-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B-6, and vitamin B-12) and Alzheimer disease (AD) remains inconclusive. OBJECTIVES: This study aimed to investigate the association of dietary OCM nutrients with subsequent risk of AD and further assess whether participants with high genetic risk for AD might benefit from dietary OCM nutrients. METHODS: We analyzed data from 192,214 participants who completed at least one 24-h dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson's The Composition of Food and USDA's Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations. RESULTS: Over a median follow-up of 13.35 y, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared with those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for methionine, folate, vitamin B-6, and vitamin B-12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B-12 intake were associated with 70% (HR: 0.30; 95% CI: 0.10, 0.86) and 71% (HR: 0.29; 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had >75% reduced AD risk compared with high-risk, low-intake participants. CONCLUSIONS: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with reduced risk of AD. Participants with high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake.

Polyphenolic truxillic acid crosslinked sodium alginate film with notable antimicrobial and biodegradable properties for food packaging.

This work demonstrated an innovative antimicrobial and biodegradable food packaging film CBDA-10-SA which was prepared by crosslinking a natural polyphenolic truxillic acid (cyclobutane-dicarboxylic acid, CBDA-10) and sodium alginate (SA). The CBDA-10-SA film exhibited improved tensile strength (148 MPa) and UV shielding capabilities. The maximum thermal decomposition temperature was achieved of 249 °C. Compared to SA film, CBDA-10-SA showed increased antibacterial activities. In food packaging test, the CBDA-10-SA inhibited the rapid growth of potential of hydrogen (pH) value, slowed down the weight loss, reduced total plate count (TPC) value of pork, and delayed the spoilage process of pork. Notably, CBDA-10-SA displayed remarkable degradability in soil, with 60 % degrading in four weeks. In this study, CBDA-10-SA showed enhanced physicochemical and mechanical properties compared to traditional SA film. Those improvements make it anticipated to be used in not only food packaging but also mechanical, pharmaceutical, and agricultural fields.

Study of aging mechanisms in LiFePO4 batteries with various SOC levels using the zero-sum pulse method.

Investigating the correlation between aging mechanisms and state of charge (SOC) can optimize cycling conditions and prolong the life cycle of lithium-ion batteries (LIBs). A long-term cycle between a certain SOC range is usually employed to study this correlation. However, this method necessitates a lengthy period, running from months to years, prolonging the research duration significantly. The aging mechanisms obtained through this method are a result of the coupling of various SOC levels; the aging mechanisms at a specific SOC level are not accurately decoupled and analyzable. The proposed Zero-sum pulse method, using symmetrical pulses with small SOC amplitude variations on SOC, can explore aging mechanisms of LIBs at a specific SOC level and reduce the time to less than a week, which significantly expedite the research process. The aging mechanisms at 30%, 50%, 70%, and 90% SOC levels are explored to verify the accuracy and timeliness of this method.

Strong third-order nonlinearity in amorphous silicon carbide waveguides.

Silicon carbide (SiC) photonic integrated platform has attracted significant research interest for on-chip optical applications, owing to its exceptional optical properties such as a broad transparency window, high refractive index, and strong nonlinearity. Among the various types of SiC, amorphous SiC (a-SiC) has particularly emerged as an accessible choice for forming thin-film SiC-on-insulator (SiCOI) stacks, demonstrating promising capabilities for wafer-scale photonic applications. In this work, we prepare three a-SiCOI samples using the plasma-enhanced chemical vapor deposition, with different refractive indices. We fabricate optical waveguides, conduct four-wave mixing measurements, and characterize the nonlinear refractive index in these samples. Our findings reveal that an increase in the refractive index of a-SiC leads to a corresponding increase in the nonlinear refractive index, which is comparable to that of silicon. Hence, a-SiC offers an approach to develop a SiC platform with a wider bandgap than that of silicon, minimizing two-photon absorption while also providing a higher refractive index and stronger nonlinearity compared to crystalline SiC.

Case report: A case of Savolitinib in the treatment of MET amplification mutation advanced lung adenocarcinoma with rare bilateral breast metastasis.

Background: The distant metastasis of lung cancer primarily occurs in the bones, liver, brain, and lungs, while the breast is an extremely rare site of metastasis. There is very limited literature on the occurrence of breast metastasis from lung cancer, and metastatic lesions in the breast are prone to being misdiagnosed as primary breast cancer, requiring careful attention and differentiation in the clinical diagnostic and treatment process. Case summary: The patient, a 63-year-old female, initially presented with an EGFR exon 21 L858R mutated left lung adenocarcinoma in 2017, treated successfully with surgical resection and subsequent monitoring. The relapse of disease occurred in January 2020. Despite maintaining a prolonged progression-free survival (PFS) with first-generation EGFR-TKI Afatinib, disease progression occurred in 2022 without detectable resistance mutations. Transition to second-generation TKI Furmonertinib resulted in poor control, with rapid progression including unusual bilateral breast metastases that exhibited inflammatory breast cancer-like peau d'orange changes. Standard chemotherapy achieved only short-term stability. Upon detecting a MET amplification mutation, treatment with Savolitinib was initiated. Remarkably, this led to significant clinical and radiographic improvement, notably resolving the peau d'orange appearance and reducing multiple lesions across the body. Conclusion: This case underscores the importance of continuous genetic profiling and tailored treatment approaches in managing advanced lung adenocarcinoma, particularly when presenting with rare metastatic sites and complex genetic landscapes. The successful application of Savolitinib following the identification of a MET amplification mutation highlights its potential in overcoming resistance mechanisms in NSCLC, providing a significant therapeutic option for similarly challenging cases.

Improved physicochemical and functional properties of dietary fiber from matcha fermented by Trichoderma viride.

The low-grade matcha is rich in insoluble dietary fiber. Trichoderma viride was used to increase the soluble dietary fiber to improve its functional properties. The soluble dietary fiber content increased from 6.74% to 15.24%. Pectin, hemicellulose, maltose, d-xylose, and glucose contents increased by 63.35% and 11.54%, 2.18, 0.11, and 7.04 mg/g, respectively. Trichoderma viride fermentation disrupted the dense structure of insoluble dietary fiber, resulting in a honeycomb structure and improving crystallinity by 22.75%. These structural changes led to an improved cation exchange capacity from 1.69 to 4.22 mmol/g, an increase in the inhibitory effect of α-amylase from 47.38% to 72.04%, and a 2.13-fold in the ferrous ion scavenging ability, and the IC50 values of superoxide anion was reduced from 7.00 to 1.54 mg/mL, respectively. Therefore, Trichoderma viride fermentation is an excellent method for improving the quality of dietary fiber in matcha processing by-products.

SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study.

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.

Application of indocyanine green-labeled fluorescence technology in laparoscopic total extra-peritoneal inguinal hernia repair surgery:a preliminary study.

BACKGROUND: Laparoscopic Total Extra-peritoneal Inguinal Hernia Repair(TEP) presents escalated risks of surgical complications, notably bleeding, particularly in European Hernia Society (EHS) types 3 and recurrent inguinal hernia. In this study, we introduced an innovative technique using indocyanine green-labeled fluorescence laparoscopy to mitigate intraoperative complications, including bleeding and rupture of the hernial sac. METHODS: This retrospective study reviewed records of 17 patients who underwent TEP repair at Anqing Municipal Hospital between July and August 2023. Intraoperatively, fluorescence imaging was utilized to trace the pathway of the spermatic vessels and outline the boundaries of the hernia sac to facilitate a thorough dissection. RESULTS: The procedure was successfully completed in all 17 patients, with a median operation time of 42 min (range: 30-51 min). Median intraoperative blood loss was 5 ml (range: 3-8 ml). Complete dissection of the hernia sac was achieved in each case without any incidents of sac rupture. Hemodynamic parameters of blood flow within the spermatic artery on postoperative day 1 showed no statistically significant deviations from the preoperative values. Furthermore, during the 7-month follow-up period, there were no cases of seroma formation or hernia recurrence. CONCLUSION: Our findings suggest that employing indocyanine green-labeled fluorescence technology in TEP repair significantly reduces intraoperative complications, notably bleeding and rupture of the hernial sac. This technique demonstrated a negligible impact on the hemodynamic parameters of the spermatic artery and reduced the overall surgical time.

Naringin inhibits cisplatin resistance of ovarian cancer cells by inhibiting autophagy mediated by the TGF-ß2/smad2 pathway.

Background: Resistance to cisplatin (DDP) in patients with ovarian cancer (OC) poses a great challenge to improving the quality of life of patients. Past reports have revealed that naringin can induce apoptosis of OC cells and delay the occurrence of drug resistance in OC cells. However, the molecular role by which naringin inhibits DDP resistance in OC has not been definitively proven by researchers. The objective of this study is to investigate the effect of naringin on DDP resistance in OC cells and the specific mechanism of naringin mediating autophagy. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were selected to evaluate the role of naringin or DDP on the proliferation and apoptosis of human OC cells (SKOV3/A2780). The protein levels of Sequestosome 1 (SQSTM1/p62, hereinafter referred to as p62), microtubule-associated protein 1 light chain 3 (LC3), transforming growth factor-ß2 (TGF-ß2) and SMAD family member 2 (smad2) were detected with Western blotting assay. Immunofluorescence assay was also used to evaluate the level of LC3 in different groups of cells. Besides, functional analyses were performed in vivo. Results: Naringin was shown to promote DDP sensitivity and apoptosis of human OC DDP-resistant cell line (SKOV3/A2780-DDP cells). Significantly increased p62 expression and reduced LC3 expression were found in naringin-treated cells. The autophagy agonist, rapamycin, reversed the effect of naringin on the resistance of SKOV3-DDP cells to DDP. Naringin inhibited levels of TGF-ß2/smad2 pathway-related proteins, and regulated autophagy in SKOV3-DDP cells. In vivo experiments demonstrated that injection of naringin inhibited DDP resistance and autophagy in mice xenograft model. Conclusions: In summary, naringin inhibits DDP resistance in OC cells by inhibiting autophagy mediated by the TGF-ß2/smad2 pathway.

Value of negative pressure sealing drainage on wound healing of Gustilo IIIB and IIIC open fractures.

BACKGROUND: Gustilo III fractures have a high incidence and are difficult to treat. Patients often experience difficulty in wound healing. Negative pressure drainage technology can help shorten wound healing time and has positive value in improving patient prognosis. AIM: To explore the clinical value of the negative pressure sealing drainage technique in wound healing of Gustilo IIIB and IIIC open fractures. METHODS: Eighty patients with Gustilo IIIB and IIIC open fractures with skin and soft tissue injuries who were treated in the Second People's Hospital of Dalian from March 2019 to December 2021 were selected as the research subjects. They were divided into a study group (n = 40, healed with negative pressure closed drainage) and a control group (n = 40, healed with conventional dressing changes) according to the variation in the healing they received. The efficacy of the clinical interventions, the variations in the regression indicators (time to wound healing, time to fracture healing, time to hospitalization), and the conversion and healing of bacterial wounds were compared 1-3 mo after the intervention. RESULTS: The total effective rate of patients among the study group was 95.00% (38/40), which was notably higher than 75.00% (30/40) among the control group (P < 0.05). The wound healing time, fracture healing time, and hospital stay of the patients in the study group was shorter than the control group (P < 0.05). After the intervention, the negative bacterial culture at the wound site rate and wound healing rate of the patients among the study group increased compared to the control group (P < 0.05). CONCLUSION: Negative pressure sealing and drainage technology has a good therapeutic effect on patients with Gustilo IIIB and IIIC open fracture wounds with skin and soft tissue injury. It can notably enhance the wound healing rate and the negative rate of bacteria on the wound surface and help to speed up the recovery process of patients.

Selective Activation of Lattice Oxygen Site Through Coordination Engineering to Boost the Activity and Stability of Oxygen Evolution Reaction.

Although Ru-based materials are among the outstanding catalysts for the oxygen evolution reaction (OER), the instability issue still haunts them and impedes the widespread application. The instability of Ru-based OER catalysts is generally ascribed to the formation of soluble species through the over-oxidation of Ru and structural decomposition caused by involvement of lattice oxygen. Herein, an effective strategy of selectively activating the lattice oxygen around Ru site is proposed to improve the OER activity and stability. Our synthesized spinel-type electrocatalyst of Ru and Zn co-doped Co3O4 showed an ultralow overpotential of 172 mV at 10 mA cm-2 and a long-term stability reaching to 100 hours at 10 mA cm-2 for alkaline OER. The experimental results and theoretical simulations demonstrated that the lattice oxygen site jointly connected with the octahedral Ru and tetrahedral Zn atoms became more active than other oxygen sites near Ru atom, which further lowered the reaction energy barriers and avoided generating excessive oxygen vacancies to enhance the structural stability of Ru sites. The findings hope to provide a new perspective to improve the catalytic activity of Ru-incorporated OER catalysts and the stability of lattice-oxygen-mediated mechanism.