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Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

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BACKGROUND: Advancements in laparoscopic technology have popularized laparoscopic total gastrectomy over traditional open surgery, yet postoperative complications like anastomotic leakage and stenosis persist, particularly in esophagojejunostomy. To address this, since 2017, the authors have introduced the "Pant-Shaped" esophagojejunostomy as an improvement over the classic Roux-en-Y method, especially beneficial for patients with small intestinal diameters or those with gastric body cancer or Siewert III. OBJECTIVE: To assess the viability and safety of employing 'Pant-Shaped' anastomosis following laparoscopic-assisted total gastrectomy. METHODS: A method of descriptive case study was used. In our department of the First Affiliated Hospital of Wannan Medical College, records of 210 patients who underwent laparoscopic-assisted total gastrectomy for gastric body cancer or adenocarcinoma at the junction of esophagus and jejunum with "Pant-Shaped" anastomosis between January 2017 and December 2022 were examined. Clinicopathological features and postoperative conditions were also examined and assessed. RESULTS: The mean age of the 164 male and 46 female research participants was 69.2 ± 8.3 years. There was a mean estimated blood loss of 63.4 ± 29.7 ml, an anastomosis time of 25.9 ± 3.0 minutes, an operation time of 208.2 ± 40.4 minutes, and a postoperative hospital stay of 12.2 ± 8.0 days. Nine patients (4.3%) experienced postoperative problems (Clavien-Dindo > grade II), including two episodes of anastomotic leakage that were resolved with irrigation and drainage, anti-infection therapy, and nutritional assistance. After an unforeseen reoperation, two cases of duodenal stump leaking were resolved. Anastamotic hemorrhage was treated with hemostasis and blood transfusion, and the patient made a full recovery. Due to a Peterson's hernia, one patient required emergent open surgery. three months subsequent to LATG. CONCLUSIONS: The "Pant-Shaped" anastomosis method after laparoscopic-assisted total gastrectomy is simple, easy to promote, and has fewer complications. It is a safe and feasible modified method for esophagojejunostomy, especially suitable for patients with poor intestinal dilation and contraction ability and small jejunal diameter.

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The application of flavoring ingredients like menthol in the food industry is hindered by their high volatility and poor thermal stability, which lead to significant losses during processing and storage. Encapsulation of flavors into porous materials to obtain inclusion complexes (ICs) has proved to be an efficient strategy. In the present study, we synthesized a series of relatively food-safe three-dimensional anionic cyclodextrin-based covalent organic frameworks (CD-COFs) with spiroborate linkages using a facile microwave-assisted method. The high surface area and newly formed cavitied of COFs significantly enhanced the encapsulation efficiency of menthol compared to native CD materials. Our findings revealed that γ-CD-COF-Li, with Li+ as the counterion, achieved superior encapsulation efficiency of 25.9%, outperforming γ-CD-COF-Na, γ-CD-COF-K and α-CD-COF-Li under the same conditions. Thermal stability measurements show that the menthol/γ-CD-COF-Li-ICs effectively stabilize menthol against heat evaporation at elevated temperatures due to the strengthened interaction between menthol and γ-CD-COF-Li. The promising results of this research suggest that rapid advancements in COF technology will provide new opportunities for enhancing the stability of flavoring ingredients in the food industry.

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Listeriosis is highly prevalent in the animal farming industry, with Listeria monocytogenes as the causative pathogen. To identify potential therapeutic targets for LM infection, we investigated the mechanisms of LM infection in goat uteri. We inoculated a group of goats with LM via jugular vein injection, isolated and raised them, and subsequently collected sterile samples of their uterine tissue after they exhibited clinical symptoms of LM infection. We used Giemsa staining, immunohistochemical staining, real-time qPCR, and Western blotting as experimental methods.First, we investigated the mechanism of Listeria monocytogenes (LM) infection in the goat uterus by examining the expression levels of listeriolysin O, E-cadherin, and tyrosine kinase c-Met in the uterus.Furthermore, we investigated the impact of LM infection on uterine autophagy and cell apoptosis. The results indicate that the injection of LM into the goats' jugular veins leads to LM infection in the goats' uteri. During LM survival inside the goat uterine cells, there is a significant increase in the expression levels of LLO, E-cadherin, and c-Met in the host uterine tissue. This suggests that LM may potentially infect goat uteri through the InlA/E-cadherin and InlB/c-Met pathways. Furthermore, LM infection increases the levels of apoptosis and autophagy in goat uteri. Apoptosis genes Bcl-2 and Bax, as well as autophagy-related genes LC3B, PINK1, and Parkin, exhibit varying degrees of changes in localization and expression in goat uteri, mediating the occurrence of apoptotic and autophagic responses.

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Mesoporous single crystals have received more attention than ever in catalysis-related applications due to their unique structural functions. Despite great efforts, their progress in engineering crystallinity and composition has been remarkably slower than expected. In this manuscript, a template-free strategy is developed to prepare two-dimensional high-entropy oxide (HEO) nanoplates with single-crystallinity and penetrated mesoporosity, which further ensures precise control over high-entropy compositions and crystalline phases. Single-crystalline mesoporous HEOs (SC-MHEOs) disclose high electrocatalytic performance in 5-hydroxymethylfurfural oxidation reaction (HMFOR) for efficient biomass upgrading, with remarkable HMF conversion of 99.3% and superior 2,5-furandicarboxylic acid (FDCA) selectivity of 97.7%. Moreover, with nitrate reduction as coupling cathode reaction, SC-MHEO realizes concurrent electrosynthesis of value-added FDCA and ammonia in the two-electrode cell. Our study provides a powerful paradigm for producing a library of novel mesoporous single crystals for important catalysis-related applications, especially in the two-electrode cell.

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For lengthening irregular bones, such as calcaneus, there are few reports in the literature. This study aimed to introduce the treatment strategy and preliminary outcomes for calcaneus shortening using calcaneal body lengthening. From January 2017 to January 2022, calcaneal lengthening was conducted for three patients (two males and one female) who suffered from traumatic calcaneal shortening. The Achilles tendon was lengthened in one patient. After osteotomy of the calcaneus, an Ilizarov frame was used to gradually (1 mm/day) distract the calcaneal fragment. The lengthening procedure was stopped when the calcaneal height and length were restored based on radiography. The fixator was removed after bone union. The average follow-up length was 18 months (range, 14-24 months). X-ray was used for radiological assessments. Patients reported satisfaction using the 100-mm visual analog scale (VAS). Clinical outcome was evaluated following the American Orthopedic Foot and Ankle score. All data were assessed by two physicians blind to clinical assessments. The wound healed primarily in three cases. The bone got solid union without refracture and malunion. The distraction time was 30 days (range, 25-45 days). The fixation time was 113.3 days (average, 80-150 days). Calcaneal lengthening was 26 mm (range, 15-43 mm). The height and length of the calcaneus were restored nearly to the same as the opposite foot. The mean preoperative calcaneal pitch angle increased from 2.6 degrees to an average of 19.0 degrees after the surgery. The AOFAS score increased from 60.0 to 86.0. One patient experienced pin infection. The infection healed after changing the dressing. Calcaneal lengthening using an Ilizarov external fixator is a preferable technique to restore the length and height of the calcaneus and can achieve satisfactory foot function.

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With the growing demand for sustainable development, tobacco stalks, as a resource-rich and low-cost renewable resource, hold the potential for producing high-value chemicals and materials within a circular economy. Due to the complex and unique structure of tobacco stalk biomass, traditional methods are ineffective in its utilization, making the pretreatment of tobacco stalk lignocellulose a crucial step in obtaining high-value products. This paper reviews recent advancements in various pretreatment technologies for tobacco stalk lignocellulosic biomass, including hydrothermal, steam explosion, acid, alkaline, organic solvent, ionic liquid, and deep eutectic solvent pretreatment. It emphasizes the impact and efficiency of these pretreatment methods on the conversion of tobacco stalk biomass and discusses the advantages and disadvantages of each technique. Finally, the paper forecasts future research directions in the pretreatment of tobacco stalk lignocellulose, providing new insights and methods for enhancing its efficient utilization.

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The development of active and selective metal electrocatalysts for complete ethanol oxidation reaction (EOR) into desired C1 products is extremely promising for practical application of direct ethanol fuel cells. Despite some encouraging achievements, their activity and selectivity remain unsatisfactory. In this work, it is reported that 2D PtRhPb mesoporous nanosheets (MNSs) with anisotropic structure and surface-clean metal site perform perfectly for complete EOR electrocatalysis in both three-electrode and two-electrode systems. Different to the traditional routes, a selective etching strategy is developed to produce surface-clean mesopores while retaining parent anisotropy quasi-single-crystalline structure without the mesopore-forming surfactants. This method also allows the general synthesis of surface-clean mesoporous metals with other compositions and structures. When being performed for alkaline EOR electrocatalysis, the best PtRhPb MNSs deliver remarkably high activity (7.8 A mg-1) and superior C1 product selectivity (70% of Faradaic efficiency), both of which are much better than reported electrocatalysts. High performance is assigned to multiple structural and compositional synergies that not only stabilized key OHads intermediate by surface-clean mesopores but also separated the chemisorption of two carbons in ethanol by adjacent Pt and Rh sites, which facilitate the oxidation cleavage of stable C─C bond for complete EOR electrocatalysis.

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Two-dimensional molybdenum disulfide (MoS2) has been proven to be a candidate in photodetectors, and MoS2/lead sulfide (PbS) quantum dots (QDs) heterostructure has been used to expand the optical response wavelength of MoS2. Time-resolved pump-probe transient absorption measurements are performed to clarify the carrier transfer dynamics in the MoS2/PbS heterostructure. By comparing the carrier dynamics in MoS2 and MoS2/PbS under different pump wavelengths, we found that the excited electrons in PbS QDs can transfer rapidly (<100 fs) to MoS2, inducing its optical response in the near-infrared region, although the pump light energy is lower than the bandgap of MoS2. Besides, interfacial excitons can be formed in the heterostructure, prolonging the lifetime of the excited carriers, which could be beneficial for the extraction of the carriers in devices.

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USP1 has emerged as a novel and potential target for drug discovery in single therapeutic agents or combination with chemotherapy and molecular targeted therapy. In this study, based on the disclosed structure of ML323 and KSQ-4279, we designed and synthesized a series of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors by cyclization strategy and the systematic structure-activity relationship exploration was conducted. The representative compounds 1k, 1m and 2d displayed excellent USP1/UAF inhibition and exhibited strong antiproliferation effect in NCI-H1299 cells. Further flow cytometry analysis revealed that they could arrest breast cancer cells MDA-MB-436 in the S phase. Inhibition mechanism study of compound 1m indicated these derivatives acted as reversible and noncompetitive USP1 inhibitors. Of note, the combination of compound 1m with PARP inhibitor olaparib generated enhanced cell killing in olaparib-resistant MDA-MB-436/OP cells, and compound 1m exhibited excellent oral pharmacokinetic properties in mice. Overall, our efforts may provide a reliable basis for the development of novel USP1 inhibitor as a single therapeutic agent and in combination with PARP inhibitors.

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OBJECTIVES: We aimed to investigate the influence of preoperative antituberculosis chemotherapy duration on perioperative epididymectomy complications in patients with epididymal tuberculosis (ETB). METHODS: This retrospective study examined patients with ETB between January 1, 2013, and March 31, 2023, who underwent unilateral epididymectomy at our hospital. We selected preoperative antituberculosis chemotherapy duration of 2, 4, and 8 weeks as the cutoffs for this study, to explore whether there are differences in the incidence of intraoperative and 30-day postoperative complications among the patients with different preoperative antituberculosis chemotherapy durations. Intraoperative complications were graded according to the Satava classification, and 30-day postoperative complications were defined according to the Clavien-Dindo classification. The study groups were compared using the unpaired t-test, Wilcoxon rank-sum test, Pearson's chi-square test, or Fisher's exact test, as appropriate. RESULTS: Overall, 155 patients were included. Statistical analysis revealed that there were no significant differences in the incidence of intraoperative and 30-day postoperative complications between patients with shorter preoperative antituberculosis chemotherapy duration and those with longer preoperative antituberculosis chemotherapy duration. CONCLUSIONS: In patients with ETB, preoperative antituberculosis chemotherapy duration did not significantly affect the incidence of perioperative complications after epididymectomy.

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Metabolic acidosis-induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end-stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH-responsive luminescent gold nanoparticles (p-AuNPs) in the second near-infrared emission co-coated with 2,3-dimethylaleic anhydride conjugated ß-mercaptoethylamine and cationic 2-diethylaminoethanethiol hydrochloride, which showed sensitive pH-induced charge reversal and intrarenal self-assembly for highly sensitive and long-time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH-induced intrarenal self-assembly and enhanced interactions between pH-triggered positively charged p-AuNPs and renal tubular cells, the early- and late-stage MAKI could be differentiated rapidly within 10 min post-injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p-AuNPs were demonstrated to effectively real-time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH-responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early-stage diagnosis of pH-related diseases.

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R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (m6A). Yet, m6A-modified R-loops in regulating gene transcription remains poorly understood. Here, we demonstrated that insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) recognize R-loops in an m6A-dependent way. Consequently, IGF2BPs overexpression leads to increased overall R-loop levels, cell migration inhibition, and cell growth retardation in prostate cancer (PCa) via precluding the binding of DNA methyltransferase 1(DNMT1) to semaphorin 3 F (SEMA3F) promoters. Moreover, the K homology (KH) domains of IGF2BPs are required for their recognition of m6A-containing R-loops and are required for tumor suppressor functions. Overexpression of SEMA3F markedly enhanced docetaxel chemosensitivity in prostate cancer via regulating Hippo pathway. Our findings point to a distinct R-loop resolution pathway mediated by IGF2BPs, emphasizing the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology.The manuscript summarizes the new role of N6-methyladenosine in epigenetic regulation, we introduce the distinct R-loop resolution mediated by IGF2BP proteins in an m6A-dependent way, which probably lead to the growth retardation and docetaxel chemotherapy resistance in prostate cancer. Moreover, our findings first emphasized the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis, indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer.

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Electrochemical upcycling of waste pollutants into high value-added fuels and/or chemicals is recognized as a green and sustainable solution that can address the resource utilization on earth. Despite great efforts, their progress has seriously been hindered by the lack of high-performance electrocatalysts. In this work, bimetallic PdCu mesoporous nanocavities (MCs) are reported as a new bifunctional enzymatic electrocatalyst that realizes concurrent electrocatalytic upcycling of nitrate wastewater and polyethylene terephthalate (PET) plastic waste. Abundant metal mesopores and open nanocavities of PdCu MCs provide the enzymatic confinement of key intermediates for the deeper electroreduction of nitrate and accelerate the transport of reactants/products within/out of electrocatalyst, thus affording high ammonia Faradic efficiency (FENH3) of 96.6% and yield rate of 5.6 mg h-1 mg-1 at the cathode. Meanwhile, PdCu MC nanozymes trigger the selective electrooxidation of PET-derived ethylene glycol (EG) into glycolic acid (GA) and formic acid with high FEs of >90% by a facile regulation of potentials at the anode. Moreover, concurrent electrosynthesis of value-added NH3 and GA is disclosed in the two-electrode coupling system, further confirming the high efficiency of bifunctional PdCu MC nanozymes in producing value-added fuels and chemicals from waste pollutants in a sustainable manner.

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Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.

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A trade-off of activity-selectivity exists in primary C-O hydrogenolysis of biomass-derived diols to secondary alcohols over bimetallic catalysts, especially the combination of noble metal and early transition metal in the metallic state and metal oxide state, respectively. Herein, the combination of high surface concentration of boron nitride (BN)-supported metals and the addition of Mo as third metal broke the trade-off. High yields (>50%) of secondary alcohols were obtained with robust productivity up to 25-fold based on Ir over Ir-Fe0.13-Mo0.08/BN (Ir = 20 wt %, Fe/Ir = 0.13, Mo/Ir = 0.08) than previously reported Ir-Fe catalysts. In contrast, simply increasing the loading amount of Ir-Fe catalysts or the addition of Mo species only enhanced the productivity by <2-4-fold. Various characterizations showed that large Ir loading enables the formation of condensed nanostructures (∼2 nm) on the BN support, which further alloy with Mo and Fe to form an face centred cubic (fcc)-type trimetallic alloy with surface enrichment of Fe. On the other hand, in Ir-Fe0.25-Mo0.08/BN with lower Ir (5 wt %) and lower Ir-based activity, the Mo species were rather bound on the support surface possibly as the MoBx state. These structures were formed by simple impregnation and reduction with H2 at the reaction temperature (453 K). The high activity of Ir-Fe0.13-Mo0.08/BN (20 wt % Ir) is derived from two aspects: (1) the formation of condensed nanostructures (∼2 nm) exposing more active sites and (2) alloying with Mo to modify the electronic state of Ir to enhance the H2 activation ability, as shown by the decreased Ea (82-84 → 67 kJ mol-1).

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Paired Ga sites represented by the Ga-O-Si-O-Ga sequence were firstly formed intentionally in CHA-type zeolite frameworks via the transcription of pre-formed paired Ga species in a Ga-rich amorphous silica-gallia under seed-assisted hydrothermal conditions. Such paired Ga sites behaved as ion-exchange sites for capturing divalent cation, Co2+.

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The development of highly efficient electrocatalysts for complete oxidation of ethylene glycol (EG) in direct EG fuel cells is of decisive importance to hold higher energy efficiency. Despite some achievements, their progress, especially electrocatalytic selectivity to complete oxidated C1 products, is remarkably slower than expected. In this work, we developed a facile aqueous synthesis of Ir-doped CuPd single-crystalline mesoporous nanotetrahedrons (Ir-CuPd SMTs) as high-performance electrocatalyst for promoting oxidation cleavage of C-C bond in alkaline EG oxidation reaction (EGOR) electrocatalysis. The synthesis relied on precise reduction/co-nucleation and epitaxial growth of Ir, Cu and Pd precursors with cetyltrimethylammonium chloride as the mesopore-forming surfactant and extra Br- as the facet-selective agent under ambient conditions. The products featured concave nanotetrahedron morphology enclosed by well-defined (111) facets, single-crystalline and mesoporous structure radiated from the center, and uniform elemental composition without any phase separation. Ir-CuPd SMTs disclosed remarkably enhanced electrocatalytic activity and excellent stability as well as superior selectivity of C1 products for alkaline EGOR electrocatalysis. Detailed mechanism studies demonstrated that performance improvement came from structural and compositional synergies, which kinetically accelerated transports of electrons/reactants within active sites of penetrated mesopores and facilitated oxidation cleavage of high-energy-barrier C-C bond of EG for desired C1 products. More interestingly, Ir-CuPd SMTs performed well in coupled electrocatalysis of anode EGOR and cathode nitrate reduction, highlighting its high potential as bifunctional electrocatalyst in various applications.

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Wet-tissue adhesives have long been attractive materials for realizing complicated biomedical functions. However, the hydration film on wet tissues can generate a boundary, forming hydrogen bonds with the adhesives that weaken adhesive strength. Introducing black phosphorus (BP) is believed to enhance the water absorption capacity of tape-type adhesives and effectively eliminate hydration layers between the tissue and adhesive. This study reports a composite patch integrated with BP nanosheets (CPB) for wet-tissue adhesion. The patch's improved water absorption and mechanical properties ensure its immediate and robust adhesion to wet tissues. Various bioapplications of CPB are demonstrated, such as rapid hemostasis (within ~1-2 seconds), monitoring of physical-activity and prevention of tumour-recurrence, all validated via in vivo studies. Given the good practicability, histocompatibility and biodegradability of CPB, the proposed patches hold significant promise for a wide range of biomedical applications.

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Evidence regarding the association between dietary niacin intake and chronic obstructive pulmonary disease (COPD) is limited. Our study investigates the relationship between dietary niacin intake and the prevalance and incidence of COPD in the adult population of the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Data on niacin intake were extracted through dietary intake interviews. COPD diagnoses were based on lung function, medical history, and medication usage. We analyzed the association between niacin consumption and COPD using multiple logistic regression and restricted cubic spline models. The study included 7055 adult participants, divided into COPD (n = 243; 3.44%) and non-COPD (n = 6812; 96.56%) groups. Those with COPD had lower average niacin intake (21.39 ± 0.62 mg/day) compared to the non-COPD group (25.29 ± 0.23 mg/day, p < 0.001). In the adjusted multivariable model, the odds ratios (OR) and 95% confidence intervals (CI) for COPD in the highest versus lowest quartile of dietary niacin intake were 0.55 (0.33 to 0.89, P for trend = 0.009). Subgroup analysis, after adjustment for various variables, revealed no significant interaction effects. Dietary niacin intake was inversely associated with COPD prevalence in US adults. Participants with the highest dietary niacin intake demonstrated the lowest odds of COPD. The potential of dietary niacin supplementation as a strategy to mitigate COPD warrants further investigation.

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