Highly selective urea electrooxidation coupled with efficient hydrogen evolution.

Electrochemical urea oxidation offers a sustainable avenue for H2 production and wastewater denitrification within the water-energy nexus; however, its wide application is limited by detrimental cyanate or nitrite production instead of innocuous N2. Herein we demonstrate that atomically isolated asymmetric Ni-O-Ti sites on Ti foam anode achieve a N2 selectivity of 99%, surpassing the connected symmetric Ni-O-Ni counterparts in documented Ni-based electrocatalysts with N2 selectivity below 55%, and also deliver a H2 evolution rate of 22.0 mL h-1 when coupled to a Pt counter cathode under 213 mA cm-2 at 1.40 VRHE. These asymmetric sites, featuring oxygenophilic Ti adjacent to Ni, favor interaction with the carbonyl over amino groups in urea, thus preventing premature resonant C⎓N bond breakage before intramolecular N-N coupling towards N2 evolution. A prototype device powered by a commercial Si photovoltaic cell is further developed for solar-powered on-site urine processing and decentralized H2 production.

[Effects of cortical bone thickness and jaw bone density on pain during implant surgery].

PURPOSE: To investigate the effects of different cortical bone thickness and jaw bone density at implant sites on intraoperative pain during implant surgery. METHODS: One hundred and eighty-seven patients(263 implant sites) who underwent implant placement surgery at the Fourth Affiliated Hospital of Nanchang University from August 2021 to August 2022 were selected to investigate the effects of different cortical bone thickness and jaw bone density HU values at implant sites on the anesthetic effect under local infiltration anesthesia with epinephrine in articaine. SPSS 26.0 software package was used for data analysis. RESULTS: The mean cortical bone thickness at the painful sites[(3.90±1.36) mm] was significantly greater than that at the non-painful sites [(2.24±0.66) mm], and the difference was statistically significant(P＜0.05). The differences in cortical bone thickness in the mandibular anterior, premolar, and molar regions were statistically significant in the comparison of pain and non-pain sites. The mean HU value of bone density was (764.46±239.75) for the painful sites and (612.23±235.31) for the non-painful sites, with significant difference(P＜0.05). The difference was not significant(P＞0.05) when comparing the HU values of painful sites with non-painful sites in the mandibular anterior teeth and anterior molar region, while the difference was significant(P＜0.05) when comparing the HU values of painful sites with non-painful sites in the mandibular molar region. CONCLUSIONS: Sites with large cortical bone thickness have a greater effect on blocking infiltrative anesthetic penetration and are more prone to intraoperative pain during implantation. In the mandibular anterior and premolar regions, the HU value of the implant sites had less effect on infiltrative anesthetic penetration, and the effect was greater in the mandibular molar region, and the implant sites with high HU values in the mandibular molar region were more likely to have intraoperative pain. When the cortical bone thickness in the planned implant site is greater than 3.9 mm and the mean bone density in the mandibular molar region is greater than 665 HU. If there is sufficient safe distance for hole operation, it is recommended to apply mandibular nerve block anesthesia combined with articaine infiltration anesthesia to avoid intraoperative pain and bad surgical experience for the patients.

HIV-1 Molecular Networks and Pretreatment Drug Resistance at the Frontier of Yunnan Province, China.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174), and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

Prognosis and immunotherapy in melanoma based on selenoprotein k-related signature.

Selenium and selenoproteins are closely related to melanoma progression. However, it is unclear how SELENOK affects lipid metabolism, endoplasmic reticulum stress (ERS), immune cell infiltration, survival, and prognosis in melanoma patients. Transcriptome data from melanoma patients was used to investigate SELENOK levels and their effect on prognosis, followed by an investigation of SELENOK's effects on immune cell infiltration. Furthermore, a risk model based on ERS, lipid metabolism, and immune-related genes was constructed, and its utility in melanoma prognosis was evaluated. Finally, the drug sensitivity of the risk model was analyzed to provide a reference for melanoma therapy. The results showed that melanoma with a high SELENOK level had a greater degree of immune cell infiltration and a better prognosis. Additionally, SELENOK was found to regulate ERS, lipid metabolism, and immune cell infiltration in melanoma. The risk model based on SELENOK signature genes successfully predicted the prognosis of melanoma, and the low-risk group exhibited a favorable immunological microenvironment. Furthermore, high-risk patients with melanoma were candidates for chemotherapy with RAS pathway inhibitors, whereas low-risk patients were more susceptible to routinely used chemotherapy medicines. In summary, SELENOK was shown to regulate ERS, lipid metabolism, and immune cell infiltration in melanoma, and SELENOK was positively associated with the prognosis of melanoma. The risk model based on SELENOK signature genes was valuable for melanoma prognosis and therapy.

The supraclavicular approach in the management of cervicothoracic-junction benign neurogenic tumors: A real-world analysis.

Objectives: The study objectives were to evaluate the safety, feasibility, and risk of neurologic complications with the supraclavicular approach in the operative management of cervicothoracic-junction benign neurogenic tumors. Methods: Between January 2012 and April 2023, 115 patients who underwent surgical resection for cervicothoracic-junction benign neurogenic tumors were retrospectively enrolled. Patients were divided into 3 groups based on the surgical approach: supraclavicular alone (Supraclav-Alone), n = 16; Transthoracic-Alone (video-assisted thoracoscopic surgery/Open), n = 87; and supraclavicular combined with transthoracic (Supraclav + video-assisted thoracoscopic surgery/open), n = 12. Clinicopathologic variables and postoperative morbidity including neurologic complications were summarized among the groups. Logistic regression analysis was performed to identify predictors for long-term (>6 months) brachial plexus injuries. Results: The cohort comprised 28 patients (24.3%) who underwent surgical resection using a supraclavicular approach. The Supraclav-Alone group portended the most cephalad location of tumor, the smallest pathologic tumor size, the shortest operative time, the least blood loss, and the least postoperative pain. The incidence of surgical complications, phrenic nerve neuropraxia, recurrent laryngeal nerve neuropraxia, or Horner's syndrome was similar among the groups postoperatively. However, use of the supraclavicular-alone approach (adjusted odds ratio, 0.165; 95% CI, 0.017-0.775) was a predictor for long-term brachial plexus injury complications. Among patients who experienced brachial plexus injury complications, the proportion of patients achieving complete resolution was higher among those undergoing a supraclavicular approach group (Supraclav-Alone: 80.0% vs Supraclav + video-assisted thoracoscopic surgery/Open: 60.0% vs video-assisted thoracoscopic surgery/Open: 25.8%). Conclusions: The supraclavicular approach may be a safe and feasible strategy in the management of cervicothoracic-junction benign neurogenic tumors that does not increase surgical complications and minimizes the severity of brachial plexus injury.

Clinical application of V-shaped folded submental flap in the repair of oral defect. / Våž‹æŠ˜å é¢ä¸‹çš®ç“£ä¿®å¤å£è ”ç¼ºæŸçš„ä¸´åºŠåº”ç”¨.

OBJECTIVES: The repair of small and medium-sized defects in the oral has always been a challenge, free skin flap and distal pedicled tissue flaps are difficult to meet clinical needs, and the traditional under-chin flap has the risk of donor-area injury. This study aims to investigate the efficacy of V-shaped folded submental flap in the repair of small-sized and medium-sized oral defects. METHODS: The clinical data of 28 patients with oral defect lesions, who were hospitalized in the Department of Stomatology, Third Xiangya Hospital of Central South University from March 2019 to December 2022, were retrospectively analyzed. Patients were divided into a V-shaped folded group (17 cases) and a conventional group (11 cases) according to different surgical methods. The V-shaped folded group was treated with a V-shaped folded submental flap for postoperative soft tissue repair, while the conventional group was treated with a conventional submental flap for repair. The postoperative follow-up time was 6-48 months. The survival status, repair time, and repair effect of the 2 groups were compared. RESULTS: There was no significant difference in flap survival rate, flap size, flap preparation time, repair surgery time, and postoperative hospital stay between the 2 groups (all P>0.05). At 6 months after the surgery, the V-shaped folded group had no difficulty in raising the head or everting the lower lip, no "cat ear" deformity in the submental skin. Scars in the V-shaped folding group were hidden at the lower edge of the mandible. The wound aesthetics and functional scores in the V-shaped folded group were significantly higher than those in the conventional group (both P<0.05). CONCLUSIONS: The V-shaped foldable submental flap has the advantages of flexible design, simple preparation, reliable blood supply, and protection of the donor area, which can effectively protect the appearance of the chin and avoid functional disorders.

Protein-nanoparticle co-assembly supraparticles for drug delivery: Ultrahigh drug loading and colloidal stability, and instant and complete lysosomal drug release.

Two frequent problems hindering clinical translation of nanomedicine are low drug loading and low colloidal stability. Previous efforts to achieve ultrahigh drug loading (>30 %) introduce new hurdles, including lower colloidal stability and others, for clinical translation. Herein, we report a new class of drug nano-carriers based on our recent finding in protein-nanoparticle co-assembly supraparticle (PNCAS), with both ultrahigh drug loading (58 % for doxorubicin, i.e., DOX) and ultrahigh colloidal stability (no significant change in hydrodynamic size after one year). We further show that our PNCAS-based drug nano-carrier possesses a built-in environment-responsive drug release feature: once in lysosomes, the loaded drug molecules are released instantly (<1 min) and completely (∼100 %). Our PNCAS-based drug delivery system is spontaneously formed by simple mixing of hydrophobic nanoparticles, albumin and drugs. Several issues related to industrial production are studied. The ultrahigh drug loading and stability of DOX-loaded PNCAS enabled the delivery of an exceptionally high dose of DOX into a mouse model of breast cancer, yielding high efficacy and no observed toxicity. With further developments, our PNCAS-based delivery systems could serve as a platform technology to meet the multiple requirements of clinical translation of nanomedicines.

Comparative Epigenetic Profiling Reveals Distinct Features of Mucosal Melanomas Associated with Immune Cell Infiltration and Their Clinical Implications.

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomic sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 patients with mucosal melanoma, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared with NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of patients with PMME and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T-cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma. SIGNIFICANCE: This study investigated the intricate epigenetic factor of mucosal melanomas contributed to the differential immune checkpoint inhibitor response, and found that PMME exhibited a global hypermethylation pattern and lower gene expression in comparison to NEMM. TERT hypermethylation may contribute to the favorable responses observed in patients with mucosal melanoma undergoing immunotherapy.

Safety and efficacy of delayed completion lobectomy following wedge resection vs. segmentectomy-a retrospective cohort study.

Background: Data regarding the safety and efficacy of delayed completion lobectomy (CL) following sublobar resections remain scant. We evaluated the technical difficulty and short-term outcomes of CL occurring at least 3 months following the anatomical segmentectomy or wedge resection. Methods: Consecutive non-small cell lung cancer (NSCLC) patients who underwent a second resection within the same lobe at least 3 months after their initial resection from January 2013 to December 2019 at the Shanghai Pulmonary Hospital were retrospectively included. The patients were divided into a segmentectomy group (SG group) and a wedge resection group (WR group) based on their initial resection strategy. Baseline characteristics and short-term outcomes after CL between the two groups were compared. Results: Twenty-five patients undergoing CL were included, nine in the SG group and 16 in the WR group. No deaths occurred within 30 days postoperatively, and the rate of overall postoperative complications was 28.0% (7/25). Statistically significant differences were found in rates of postoperative complications between the two groups (SG: 55.6% vs. WR: 12.5%, P=0.03) and in the use of bronchoplasty or angioplasty during the CL (SG: 33.3% vs. WR: 0.0%, P=0.04). After CL, no significant differences were found in 5-year recurrence-free survival (RFS) (WR: 66.7% vs. SG: 61.0%, P=0.31) or overall survival (OS) (WR: 93.8% vs. SG: 66.7%, P=0.06) between two groups. Conclusions: Delayed CL occurring over 3 months after sublobar resection is a safe and effective procedure, with no deaths occurring within 30 days postoperatively. As compared to a segmentectomy at the time of the index operation, a wedge resection may portend less morbidity, with a decreased risk of needing adjunctive bronchoplasty or angioplasty procedures during CL. After CL, 5-year RFS and OS were comparable between WR and SG groups.

Monodispersed and Organic Amine Modified La(OH)3 Nanocrystals for Superior Advanced Phosphate Removal.

Advanced phosphate removal is critical for alleviating the serious and widespread aquatic eutrophication, strongly depending on the development of superior adsorption materials to overcome low chemical affinity and sluggish mass transfer at low phosphate concentrations. Herein, the first synthesis of monodispersed and organic amine modified lanthanum hydroxide nanocrystals (OA-La(OH)3) for advanced phosphate removal by modulating inner Helmholtz plane (IHP), is reported. These OA-La(OH)3 nanocrystals with positively charged surfaces and abundant exposed La sites exhibit specific affinity toward phosphate, delivering a maximum adsorption capacity of 168 mg P g⁻1 and a wide pH adaptability from 3.0 to 11.0, as well as a robust anti-interference performance, far surpassing those of documented phosphate removal materials. The superior phosphate removal performance of OA-La(OH)3 is attributed to its protonated organic amine in IHP, which enhances the electrostatic attraction around the adsorbent-solution interface. Impressively, OA-La(OH)3 can treat ≈5 000 and ≈3 200 bed volumes of simulated and real phosphate-containing wastewater to below extremely strict standard (0.1 mg L⁻1) in a fixed-bed adsorption mode, exhibiting great potential for advanced phosphate removal. This study offers a facile modification strategy to improve phosphate removal performance of nanoscale adsorbents, and sheds light on the structure-reactivity relationship of La-based materials.

Effect of NLRP3 Inflammasome on Lung Cancer Immune Microenvironment Activation and Its Mechanism.

Objective: The NLRP3 inflammasome plays a dual role in the occurrence and development of tumors, and its role in lung cancer remains unclear. This study aims to investigate the impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells. Methods: Data from the GEPIA, TCGA, and HPA databases were utilized to analyze the expression of NLRP3 in lung adenocarcinoma and its microenvironment. GO/KEGG enrichment analysis and GSEA analysis were employed to annotate the functions of differentially expressed genes related to NLRP3. The impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells was further investigated by CCK-8 assay and scratch assay. The effects of blocking NLRP3 inflammasome activation with IL-1RA and IL-18BP on the proliferation and migration of lung cancer cells were further assessed. Survival analysis was conducted to analyze the impact of NLRP3 expression on the prognosis of patients with lung adenocarcinoma. Results: The expression of NLRP3 in lung cancer was lower than in normal tissues, with notably higher expression observed in macrophages compared to other cells. Patients with higher NLRP3 expression exhibit increased infiltration of M2 macrophages. Activation of the NLRP3 inflammasome using LPS+ATP promotes the proliferation and migration of A549 cells. Simultaneous use of IL-1RA and IL-18BP reverses the promoting effect of NLRP3 inflammasome activation on cell proliferation and migration. Survival analysis results indicate that patients with high NLRP3 expression have a poorer prognosis compared to those with low NLRP3 expression (Hazzard Ratio =1.44; 95% Confidence Interval: 1.21-1.71). Conclusions: The activation of the NLRP3 inflammasome promotes the proliferation and migration of A549 cells through secretion of IL-1ß and IL-18, potentially influencing patient prognosis. Simultaneously blocking IL-1ß and IL-18 can reverse the pro-proliferative and migration-promoting effects.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

Added value of DCER-features to clinicopathologic model for predicting metachronous metastases in rectal cancer patients.

RATIONALE AND OBJECTIVES: The study aimed to investigate whether dynamic contrast-enhanced MRI parameters and preoperative radiological features (DCER-Features) add value to the clinicopathologic model for predicting metachronous metastases in rectal cancer patients. MATERIALS AND METHODS: From January 2014 to December 2020, 859 patients in the PACS system were retrospectively screened. Of the initial 722 patients with surgically confirmed rectal cancer and no synchronous metastases, 579 patients were excluded for various reasons such as lack of clinicopathological or radiological information. 143 patients were finally included in this study. And 73 Patients of them developed metachronous metastasis within five years. After stepwise multiple regression analyses, we constructed three distinct models. Model 1 was developed solely based on clinicopathological factors, and model 2 incorporated clinicopathological characteristics along with DCE-MRI parameters. Finally, model 3 was built on all available factors, including clinicopathological characteristics, DCE-MRI parameters, and radiological features based on rectal magnetic resonance imaging. The radiological features assessed in this study encompass tumor imaging staging, location, and circumferential resection margin (CRM) for primary tumors, as well as the number of visible lymph nodes and suspected metastatic lymph nodes. Receiver operating characteristic (ROC) and decision curve analysis (DCA) were conducted to evaluate whether the diagnostic efficiency was improved. RESULTS: The performance of model 3 (including clinicopathologic characteristics and DCER-Features) was the best (AUC: 0.856, 95% CI 0.778-0.886), whereas it was 0.796 (95% CI 0.720-0.828) for model 2 and 0.709 (95% CI 0.612-0.778) for model 1 (DeLong test: model 1 vs model 2, p = 0.004; model 2 vs model 3, p = 0.037; model 1 vs model 3, p < 0.001). The decision curves indicated that the net benefit of model 3 was higher than the other two models at each referral threshold. The calibration plot of the three models revealed an excellent predictive accuracy. CONCLUSION: This study suggests that DCER-Features have added value for the clinicopathological model to predict metachronous metastasis in patients with rectal cancers.

Thrombin-targeted screening of anticoagulant active components from Polygonum amplexicaule D. Don var. sinense Forb by affinity ultrafiltration coupled with UPLC-Q-TOF-MS.

INTRODUCTION: Polygonum amplexicaule D. Don var. sinense Forb (PAF), a medicinal plant, has the effect of promoting blood circulation and removing blood stasis. However, the active compounds and targets of its anticoagulant effect are still unclear. OBJECTIVES: This study aims to establish an effective reversely thrombin-targeted screening method for anticoagulant active components in PAF by affinity ultrafiltration (AUF) coupled with ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC-Q-TOF-MS). METHODS: Different polar parts of PAF were screened for potential thrombin ligands by AUF-HPLC and identified by UPLC-Q-TOF-MS. After studying the affinity between ligands and thrombin by molecular docking, the antithrombotic activity of ligands was detected in vivo by zebrafish thrombus model, and in vitro by chromogenic substrate method. The mechanism of such ligands on thrombin was further studied by coagulation factor assay. RESULTS: Eleven potential thrombin ligands from PAF were screened by the AUF-UPLC-Q-TOF-MS method, and two compounds (butyl gallate and ß-sitosterol) with significant anticoagulant activity were discovered via in vitro and in vivo activity testing. CONCLUSION: A method system based on AUF-UPLC-Q-TOF-MS, molecular docking and in vivo and in vitro experiments also provided a powerful tool for further exploration of anticoagulant active components in PAF.

Cobalt Single-Atom Reverse Hydrogen Spillover for Efficient Electrochemical Water Dissociation and Dechlorination.

Efficient water dissociation to atomic hydrogen (H*) with restrained recombination of H* is crucial for improving the H* utilization for electrochemical dechlorination, but is currently limited by the lack of feasible electrodes. Herein, we developed a monolithic single-atom electrode with Co single atoms anchored on the inherent oxide layer of titanium foam (Co1-TiOx/Ti), which can efficiently dissociate water into H* and simultaneously inhibit the recombination of H*, by taking advantage of the single-atom reverse hydrogen spillover effect. Experimental and theoretical calculations demonstrated that H* could be rapidly generated on the oxide layer of titanium foam, and then overflowed to the adjacent Co single atom for the reductive dechlorination. Using chloramphenicol as a proof-of-concept verification, the resulting Co1-TiOx/Ti monolithic electrode exhibited an unprecedented performance with almost 100 % dechlorination at -1.0 V, far superior to that of traditional indirect reduction-driven commercial Pd/C (52 %) and direct reduction-driven Co1-N-C (44 %). Moreover, its dechlorination rate constant of 1.64 h-1 was 4.3 and 8.6 times more active than those of Pd/C (0.38 h-1) and Co1-N-C (0.19 h-1), respectively. Our research sheds light on the rational design of hydrogen spillover-related electrocatalysts to simultaneously improve the H* generation, transfer, and utilization for environmental and energy applications.

Down-regulated HHLA2 enhances neoadjuvant immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. PATIENTS AND METHODS: Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy's effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. RESULTS: A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295-4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV-H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). CONCLUSIONS: The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. TRIAL REGISTRATION: Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD-associated NSCLC.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal-associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD-associated NSCLC and their involvement in the immune response. METHODS: Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti-programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5-OP-RU using a mouse subcutaneous tumor model. RESULTS: Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5-OP-RU enhanced the antitumor effects of anti-PD1. CONCLUSIONS: In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.