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Abstract Background There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets. Methods We integrated druggable genome data, cis‐eQTL/cis‐pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia‐related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome‐wide MR (Phe‐MR) approach and investigated actionable drugs for target genes using available databases. Results MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA‐DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up‐regulation of HP [higher ALM (beta: 0.012, 95% CI: 0.007–0.018, P = 1.2*10−5) and higher grip strength (OR: 0.96, 95% CI: 0.94–0.98, P = 4.2*10−5)], MAP 3K3 [higher ALM (beta: 0.24, 95% CI: 0.21–0.26, P = 1.8*10−94), higher grip strength (OR: 0.82, 95% CI: 0.75–0.90, P = 2.1*10−5), and faster walking pace (beta: 0.03, 95% CI: 0.02–0.05, P = 8.5*10−6)], and MFGE8 [higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06–0.11, P = 6.1*10−13; blood pQTL, beta: 0.05, 95% CI: 0.03–0.07, P = 3.8*10−09)], as well as the down‐regulation of HLA‐DRA [lower ALM (beta: ‐0.09, 95% CI: −0.11 to −0.08, P = 5.4*10−36) and lower grip strength (OR: 1.13, 95% CI: 1.07–1.20, P = 1.8*10−5)] and COL15A1 [higher ALM (muscle eQTL, beta: ‐0.07, 95% CI: −0.10 to −0.04, P = 3.4*10−07; blood pQTL, beta: ‐0.05, 95% CI: −0.06 to −0.03, P = 1.6*10−07)], decreased the risk of sarcopenia. AURKA in blood (beta: ‐0.16, 95% CI: −0.22 to −0.09, P = 2.1*10−06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P = 5.3*10−05) tissues showed an inverse relationship with sarcopenia risk. The Phe‐MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticum might be potential therapeutics for sarcopenia by activating HP and inhibiting COL15A1, respectively. Conclusions Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA‐DRA may serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticum for sarcopenia requires further validation.

Abstract Background The Fructus Ligustri Lucidi, the fruit of Ligustrum lucidum, contains a variety of bioactive compounds, such as flavonoids, triterpenoids, and secoiridoids. The proportions of these compounds vary greatly during the different fruit development periods of Fructus Ligustri Lucidi. However, a clear understanding of how the proportions of the compounds and their regulatory biosynthetic mechanisms change across the different fruit development periods of Fructus Ligustri Lucidi is still lacking. Results In this study, metabolite profiling and transcriptome analysis of six fruit development periods (45 DAF, 75 DAF, 112 DAF, 135 DAF, 170 DAF, and 195 DAF) were performed. Seventy compounds were tentatively identified, of which secoiridoids were the most abundant. Eleven identified compounds were quantified by high performance liquid chromatography. A total of 103,058 unigenes were obtained from six periods of Fructus Ligustri Lucidi. Furthermore, candidate genes involved in triterpenoids, phenylethanols, and oleoside-type secoiridoid biosynthesis were identified and analyzed. The in vitro enzyme activities of nine glycosyltransferases involved in salidroside biosynthesis revealed that they can catalyze trysol and hydroxytyrosol to salidroside and hydroxylsalidroside. Conclusions These results provide valuable information to clarify the profile and molecular regulatory mechanisms of metabolite biosynthesis, and also in optimizing the harvest time of this fruit.

Abstract The limited durability of metal-nitrogen-carbon electrocatalysts severely restricts their applicability for the oxygen reduction reaction in proton exchange membrane fuel cells. In this study, we employ the chemical vapor modification method to alter the configuration of active sites from FeN4 to the stable monosymmetric FeN2+N’2, along with enhancing the degree of graphitization in the carbon substrate. This improvement effectively addresses the challenges associated with Fe active center leaching caused by N-group protonation and free radicals attack due to the 2-electron oxygen reduction reaction. The electrocatalyst with neoteric active site exhibited excellent durability. During accelerated aging test, the electrocatalyst exhibited negligible decline in its half-wave potential even after undergoing 200,000 potential cycles. Furthermore, when subjected to operational conditions representative of fuel cell systems, the electrocatalyst displayed remarkable durability, sustaining stable performance for a duration exceeding 248 h. The significant improvement in durability provides highly valuable insights for the practical application of metal-nitrogen-carbon electrocatalysts.

Abstract Background Solanum aculeatissimum and Solanum torvum belong to the Solanum species, and they are essential plants known for their high resistance to diseases and adverse conditions. They are frequently used as rootstocks for grafting and are often crossbred with other Solanum species to leverage their resistance traits. However, the phylogenetic relationship between S. aculeatissimum and S. torvum within the Solanum genus remains unclear. Therefore, this paper aims to sequence the complete chloroplast genomes of S. aculeatissimum and S. torvum and analyze them in comparison with 29 other previously published chloroplast genomes of Solanum species. Results We observed that the chloroplast genomes of S. aculeatissimum and S. torvum possess typical tetrameric structures, consisting of one Large Single Copy (LSC) region, two reverse-symmetric Inverted Repeats (IRs), and one Small Single Copy (SSC) region. The total length of these chloroplast genomes ranged from 154,942 to 156,004 bp, with minimal variation. The highest GC content was found in the IR region, while the lowest was in the SSC region. Regarding gene content, the total number of chloroplast genes and CDS genes remained relatively consistent, ranging from 128 to 134 and 83 to 91, respectively. Nevertheless, there was notable variability in the number of tRNA genes and rRNAs. Relative synonymous codon usage (RSCU) analysis revealed that both S. aculeatissimum and S. torvum preferred codons that utilized A and U bases. Analysis of the IR boundary regions indicated that contraction and expansion primarily occurred at the junction between SSC and IR regions. Nucleotide polymorphism analysis and structural variation analysis demonstrated that chloroplast variation in Solanum species mainly occurred in the LSC and SSC regions. Repeat sequence analysis revealed that A/T was the most frequent base pair in simple repeat sequences (SSR), while Palindromic and Forward repeats were more common in long sequence repeats (LSR), with Reverse and Complement repeats being less frequent. Phylogenetic analysis indicated that S. aculeatissimum and S. torvum belonged to the same meristem and were more closely related to Cultivated Eggplant. Conclusion These findings enhance our comprehension of chloroplast genomes within the Solanum genus, offering valuable insights for plant classification, evolutionary studies, and potential molecular markers for species identification.

Abstract Background There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment. Methods To identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models. Results Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 [OR 1.30, 95%CI (1.19, 1.42)], TNFSF12 [OR 1.36, 95%CI (1.19, 1.56)], GPX3 [OR 1.28, 95%CI (1.15, 1.43)], TNFSF13 [OR 0.45, 95%CI (0.32, 0.64)], and CD68 [OR 0.38, 95%CI (0.24, 0.58)]. Additionally, we identified potential ALS druggable genes in the brain, including RESP18 [OR 1.11, 95%CI (1.07, 1.16)], GPX3 [OR 0.57, 95%CI (0.48, 0.68)], GDF9 [OR 0.77, 95%CI (0.67, 0.88)], and PTPRN [OR 0.17, 95%CI (0.08, 0.34)]. Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation. Conclusions Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.

Abstract CO2 hydrogenation to chemicals and fuels is a significant approach for achieving carbon neutrality. It is essential to rationally design the chemical structure and catalytic active sites towards the development of efficient catalysts. Here we show a Ce-CuZn catalyst with enriched Cu/Zn-OV-Ce active sites fabricated through the atomic-level substitution of Cu and Zn into Ce-MOF precursor. The Ce-CuZn catalyst exhibits a high methanol selectivity of 71.1% and a space-time yield of methanol up to 400.3 g·kgcat −1·h−1 with excellent stability for 170 h at 260 °C, comparable to that of the state-of-the-art CuZnAl catalysts. Controlled experiments and DFT calculations confirm that the incorporation of Cu and Zn into CeO2 with abundant oxygen vacancies can facilitate H2 dissociation energetically and thus improve CO2 hydrogenation over the Ce-CuZn catalyst via formate intermediates. This work offers an atomic-level design strategy for constructing efficient multi-metal catalysts for methanol synthesis through precise control of active sites.

Abstract Heterogeneous nano-electrocatalysts doped with nonmetal atoms have been studied extensively based on the so-called dopant-based active sites, while little attention has been paid to the stability of these dopants under working conditions. In this work, we reveal significantly, when the redox working potential is too low negatively or too high positively, the active sites based on these dopants actually tend to collapse. It means that some previously observed “remarkable catalytic performance” actually originated from some unknown active sites formed in situ. Take the Bi-F for the CO2RR as an example, results show that the observed remarkable activity and stability were not directly from F-based active sites, but the defective Bi sites formed in situ after the dopant leaching. Such a fact is unveiled from several heteroatom-doped nanocatalysts for four typical reactions (CO2RR, HER, ORR, and OER). This work provides insight into the role of dopants in electrocatalysis.

Abstract The study aimed to assess the stability of various mechanical injury techniques in creating tracheal stenosis animal models using endoscopic assistance and investigate the viability of tracheal stoma in this process. Twenty-six healthy adult New Zealand white rabbits were randomly assigned to an experimental and control group. The experimental group underwent tracheal incision followed by steel brush scraping with endoscopic assistance, while the control group received nylon brush scraping. Within the control group, two subgroups were formed: Group A underwent scraping without tracheal stoma, and Group B underwent scraping followed by tracheal stoma. Additionally, a sham operation was performed on a separate group without subsequent scratching, resulting in no stenosis formation. Endoscopic observations were conducted at 7, 14, and 21 days post-scraping, followed by histological examinations of euthanized rabbits on the 21st day. Notably, all rabbits in the non-stoma group survived without complications, whereas Group B rabbits faced mortality post-operation. Histological assessments revealed inflammatory cell infiltration, fibroblast proliferation, and collagen fiber deposition in narrowed tracheal specimens. Steel brush scraping with endoscopic assistance proved more effective in inducing stable tracheal stenosis compared to nylon brush scraping. However, the survival challenges of rabbits with tracheal fistula require further investigation.

Abstract Background Mid‐rectal cancer treatment traditionally involves conventional laparoscopic‐assisted resection (CLAR). This study aimed to assess the clinical and therapeutic advantages of Natural Orifice Specimen Extraction Surgery (NOSES) over CLAR. Aims To compare the clinical outcomes, intraoperative metrics, postoperative recovery, complications, and long‐term prognosis between NOSES and CLAR groups. Materials & Methods A total of 136 patients were analyzed, with 92 undergoing CLAR and 44 undergoing NOSES. Clinical outcomes were evaluated, and propensity score matching (PSM) was employed to control potential biases. Results The NOSES group exhibited significant improvements in postoperative recovery, including lower pain scores on days 1, 3, and 5 (p < .001), reduced need for additional analgesics (p = .02), shorter hospital stays (10.8 ± 2.3 vs. 14.2 ± 5.3 days; p < .001), and decreased intraoperative blood loss (48.1 ± 52.7 mL vs. 71.0 ± 55.0 mL; p = .03). Patients undergoing NOSES also reported enhanced satisfaction with postoperative abdominal appearance and better quality of life. Additionally, the NOSES approach resulted in fewer postoperative complications. Conclusion While long‐term outcomes (overall survival, disease‐free survival, and local recurrence rates) were comparable between the two methods, NOSES demonstrated superior postoperative outcomes compared to CLAR in mid‐rectal cancer treatment, while maintaining similar long‐term oncological safety. These findings suggest that NOSES could serve as an effective alternative to CLAR without compromising long‐term results.

IntroductionIntracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. MethodsAdult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays.ResultsOur study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. DiscussionOur findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH.

Background: Recent genetic evidence supports that circulating biochemical and metabolic traits (BMTs) play a causal role in Alzheimer's disease (AD), which might be mediated by changes in brain structure. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between blood BMTs, brain image-derived phenotypes (IDPs) and AD. Methods: Utilizing the genetic variants associated with 760 blood BMTs and 172 brain IDPs as the exposure and the latest AD summary statistics as the outcome, we analyzed the causal relationship between blood BMTs and brain IDPs and AD by using a two-sample Mendelian randomization (MR) method. Additionally, we used two-step/mediation MR to study the mediating effect of brain IDPs between blood BMTs and AD. Results: Twenty-five traits for genetic evidence supporting a causal association with AD were identified, including 12 blood BMTs and 13 brain IDPs. For BMTs, glutamine consistently reduced the risk of AD in 3 datasets. For IDPs, specific alterations of cortical thickness (atrophy in frontal pole and insular lobe, and incrassation in superior parietal lobe) and subcortical volume (atrophy in hippocampus and its subgroups, left accumbens and left choroid plexus, and expansion in cerebral white matter) are vulnerable to AD. In the two-step/mediation MR analysis, superior parietal lobe, right hippocampal fissure and left accumbens were identified to play a potential mediating role among three blood BMTs and AD. Conclusions: The results obtained in our study suggest that 12 circulating BMTs and 13 brain IDPs play a causal role in AD. Importantly, a subset of BMTs exhibit shared genetic architecture and potentially causal relationships with brain structure, which may contribute to the alteration of brain IDPs in AD.

Abstract Background More accurate prediction of distant metastases (DM) in patients with colorectal cancer (CRC) would optimize individualized treatment and follow‐up strategies. Multiple prediction models based on machine learning have been developed to assess the likelihood of developing DM. Methods Clinicopathological features of patients with CRC were obtained from the National Cancer Center (NCC, China) and the Surveillance, Epidemiology, and End Results (SEER) database. The algorithms used to create the prediction models included random forest (RF), logistic regression, extreme gradient boosting, deep neural networks, and the K‐Nearest Neighbor machine. The prediction models' performances were evaluated using receiver operating characteristic (ROC) curves. Results In total, 200,958 patients, 3241 from NCC and 197,717 CRC from SEER were identified, of whom 21,736 (10.8%) developed DM. The machine‐learning‐based prediction models for DM were constructed with 12 features remaining after iterative filtering. The RF model performed the best, with areas under the ROC curve of 0.843, 0.793, and 0.806, respectively, on the training, test, and external validation sets. For the risk stratification analysis, the patients were separated into high‐, middle‐, and low‐risk groups according to their risk scores. Patients in the high‐risk group had the highest incidence of DM and the worst prognosis. Surgery, chemotherapy, and radiotherapy could significantly improve the prognosis of the high‐risk and middle‐risk groups, whereas the low‐risk group only benefited from surgery and chemotherapy. Conclusion The RF‐based model accurately predicted the likelihood of DM and identified patients with CRC in the high‐risk group, providing guidance for personalized clinical decision‐making.

Abstract Genome‑wide association studies (GWASs) have revealed numerous loci associated with Parkinson’s disease (PD). However, some potential causal/risk genes were still not revealed and no etiological therapies are available. To find potential causal genes and explore genetically supported drug targets for PD is urgent. By integrating the expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets from multiple tissues (blood, cerebrospinal fluid (CSF) and brain) and PD GWAS summary statistics, a pipeline combing Mendelian randomization (MR), Steiger filtering analysis, Bayesian colocalization, fine mapping, Protein-protein network and enrichment analysis were applied to identify potential causal genes for PD. As a result, GPNMB displayed a robust causal role for PD at the protein level in the blood, CSF and brain, and transcriptional level in the brain, while the protective role of CD38 (in brain pQTL and eQTL) was also identified. We also found inconsistent roles of DGKQ on PD between protein and mRNA levels. Another 9 proteins (CTSB, ARSA, SEC23IP, CD84, ENTPD1, FCGR2B, BAG3, SNCA, FCGR2A) were associated with the risk for PD based on only a single pQTL after multiple corrections. We also identified some proteins’ interactions with known PD causative genes and therapeutic targets. In conclusion, this study suggested GPNMB, CD38, and DGKQ may act in the pathogenesis of PD, but whether the other proteins involved in PD needs more evidence. These findings would help to uncover the genes underlying PD and prioritize targets for future therapeutic interventions.

Abstract Background During Fritillaria thunbergii planting, pests and diseases usually invade the plant, resulting in reduced yield and quality. Previous studies have demonstrated that using biocontrol agents can effectively control grubs and affect the steroid alkaloids content in F. thunbergii. However, the molecular regulatory mechanisms underlying the differences in the accumulation of steroid alkaloids in response to biocontrol agents remain unclear. Results Combined transcriptomic and metabolic analyses were performed by treating the bulbs of F. thunbergii treated with biocontrol agents during planting. Otherwise, 48 alkaloids including 32 steroid alkaloids, 6 indole alkaloids, 2 scopolamine-type alkaloids, 1 isoquinoline alkaloid, 1 furoquinoline alkaloid, and 6 other alkaloids were identified. The content of steroidal alkaloids particularly peimine, peiminine, and veratramine, increased significantly in the group treated with the biocontrol agents. Transcriptome sequencing identified 929 differential genes using biocontrol agents, including 589 upregulated and 340 downregulated genes. Putative biosynthesis networks of steroid alkaloids have been established and combined with differentially expressed structural unigenes, such as acetyl-CoA C-acetyl-transferase, acelyl-CoAC-acetyltransferase3-hydroxy-3-methylglutaryl-coenzyme A synthase, 1-deoxy-D-xylulose-5-phosphate reductor-isomerase, 2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase. In addition, biological processes such as amino acid accumulation and oxidative phosphorylation were predicted to be related to the synthesis of steroid alkaloids. Cytochrome P450 enzymes also play crucial roles in the steroid alkaloid synthesis. The transcription factor families MYB and bHLH were significantly upregulated after using biocontrol agents. Conclusions Biocontrol agents increased the steroid alkaloids accumulation of steroid alkaloids by affecting key enzymes in the steroid alkaloid synthesis pathway, biological processes of oxidative phosphorylation and amino acid synthesis, cytochrome P450 enzymes, and transcription factors. This study revealed the mechanism underlying the difference in steroidal alkaloids in F. thunbergii after using biocontrol agents, laying the groundwork for future industrial production of steroid alkaloids and ecological planting of medicinal materials in the future.

Chamomile has become one of the world’s most popular herbal teas due to its unique properties. Chamomile is widely used in dietary supplements, cosmetics, and herbal products. This study aimed to investigate the volatile aromatic components in chamomile. Two analytical techniques, gas chromatography–mass spectrometry (GC-MS) and an ultra-fast gas chromatography electronic nose, were employed to examine samples from Xinjiang (XJ), Shandong (SD), and Hebei (HB) in China, and imported samples from Germany (GER). The results revealed that all chamomile samples contained specific sesquiterpene compounds, including α-bisabolol, bisabolol oxide, bisabolone oxide, and chamazulene. Additionally, forty potential aroma components were identified by the electronic nose. The primary odor components of chamomile were characterized by fruity and spicy notes. The primary differences in the components of chamomile oil were identified as (E)-β-farnesene, chamazulene, α-bisabolol oxide B, spathulenol and α-bisabolone oxide A. Significant differences in aroma compounds included geosmin, butanoic acid, 2-butene, norfuraneol, γ-terpinene. This study demonstrates that GC–MS and the ultra-fast gas chromatography electronic nose can preliminarily distinguish chamomile from different areas, providing a method and guidance for the selection of origin and sensory evaluation of chamomile. The current study is limited by the sample size and it provides preliminary conclusions. Future studies with a larger sample size are warranted to further improve these findings.

Abstract Aims Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE. Methods The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails. Results Five case‐control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta‐analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15–6.38, p

Abstract Background Glandular trichomes, often referred to as “phytochemical factories”, plays a crucial role in plant growth and metabolism. As the site for secretion and storage, the development of glandular trichomes is related to the dynamic biosynthesis of specialised metabolites. The study aims to explore the relationship between spatial phenotype and dynamic metabolism of glandular trichomes, and establish a novel approach for the exploration and study of the regulatory mechanism governing the development of glandular trichomes. Results In this study, we proposed a technical route based on the relative deviation value to distinguish the peltate glandular trichomes (PGTs) from the background tissues and extract their spatial phenotype. By defining glandular trichome developmental stages based on the leaf vein growth axis, we found that young PGTs were densely distributed near the proximal end of growth axis of the leaf veins, where perillaketone, a primary metabolite of PGTs, is predominantly accumulated. Conversely, mature PGTs are typically found near the distal end of the mid-vein growth axis and the lateral end of the secondary vein growth axis, where the accumulation rate of isoegomaketone and egomaketone exceeds that of perillaketone in PGTs. We further identified spatial phenotypic parameters, Lsum and d, as independent variables to construct a linear regression model that illustrates the relationship between the spatial phenotypes and metabolite content of PGTs, including perillaketone (R2 = 0.698), egomaketone (R2 = 0.593), isoegomaketone (R2 = 0.662) and the sum of the amount (R2 = 0.773). Conclusions This model proved that the development of PGTs was correlated with the growth of the entire leaf, and the development stage of PGTs can be identifined by spatial phenotypes based on the leaf veins. In conclusion, the findings of this study enhance our understanding of correlation between spatial phenotype and development of glandular trichomes and offer a new approach to explore and study the regulatory mechanism of glandular trichome development.

Abstract Covalent organic frameworks (COFs) have been well developed in electrocatalytic systems owing to their controllable skeletons, porosities, and functions. However, the catalytic process in COFs remains underexplored, hindering an in‐depth understanding of the catalytic mechanism. In this work, uniform Pt–N1O1Cl4 sites chelated via C–N and C=O bonds along the one‐dimensional and open channels of TP–TTA–COF were established. Different from conventional single‐metal sites constructed for the near‐free platinum for hydrogen evolution, the as‐constructed PtCl–COF showed 2e− oxygen reduction for H2O2 production. We tracked the dynamic evolution process of atomic Pt sites in which Pt–N1O1Cl4 was transformed into Pt–N1O1(OH)2 using in situ X‐ray adsorption. The theoretical calculations revealed that the strong Pt–support interaction in Pt–N1O1(OH)2 facilitated *OOH formation and thus led to higher selectivity and activity for the oxygen reduction reaction in the 2e− pathway. This work can expand the applications of COFs through the regulation of their local electronic states for the manipulation of the metal center.

Abstract Background Perilla frutescens is widely used as both a medicine and a food worldwide. Its volatile oils are its active ingredients, and, based on the different volatile constituents, P. frutescens can be divided into several chemotypes, with perilla ketone (PK) being the most common. However, the key genes involved in PK biosynthesis have not yet been identified. Results In this study, metabolite constituents and transcriptomic data were compared in leaves of different levels. The variation in PK levels was the opposite of that of isoegoma ketone and egoma ketone in leaves at different levels. Based on transcriptome data, eight candidate genes were identified and successfully expressed in a prokaryotic system. Sequence analysis revealed them to be double bond reductases (PfDBRs), which are members of the NADPH-dependent, medium-chain dehydrogenase/reductase (MDR) superfamily. They catalyze the conversion of isoegoma ketone and egoma ketone into PK in in vitro enzymatic assays. PfDBRs also showed activity on pulegone, 3-nonen-2-one, and 4-hydroxybenzalacetone. In addition, several genes and transcription factors were predicted to be associated with monoterpenoid biosynthesis, and their expression profiles were positively correlated with variations in PK abundance, suggesting their potential functions in PK biosynthesis. Conclusions The eight candidate genes encoding a novel double bond reductase related to perilla ketone biosynthesis were identified in P. frutescens, which carries similar sequences and molecular features as the MpPR and NtPR from Nepeta tenuifolia and Mentha piperita, respectively. These findings not only reveal the pivotal roles of PfDBR in exploring and interpreting PK biological pathway but also contribute to facilitating future studies on this DBR protein family.

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.

Abstract Introduction This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. Materials and methods A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. Results In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P

Abstract Single-site pincer-ligated iridium complexes exhibit the ability for C-H activation in homogeneous catalysis. However, instability and difficulty in catalyst recycling are inherent disadvantages of the homogeneous catalyst, limiting its development. Here, we report an atomically dispersed Ir catalyst as the bridge between homogeneous and heterogeneous catalysis, which displays an outstanding catalytic performance for n-butane dehydrogenation, with a remarkable n-butane reaction rate (8.8 mol·gIr −1·h−1) and high butene selectivity (95.6%) at low temperature (450 °C). Significantly, we correlate the BDH activity with the Ir species from nanoscale to sub-nanoscale, to reveal the nature of structure-dependence of catalyst. Moreover, we compare Ir single atoms with Pt single atoms and Pd single atoms for in-depth understanding the nature of metal-dependence at the atomic level. From experimental and theoretical calculations results, the isolated Ir site is suitable for both reactant adsorption/activation and product desorption. Its remarkable dehydrogenation capacity and moderate adsorption behavior are the key to the outstanding catalytic activity and selectivity.

Abstract Background Extracellular vesicles derived from stem cells (SC-EVs) have been proposed as a novel therapy for ischemic stroke. However, their effects remain incompletely understood. Therefore, we conducted this meta-analysis to systematically review the efficacy of SC-EVs on ischemic stroke in preclinical rodent models. Methods Using PubMed, EMBASE, and the Web of Science, we searched through studies published up to August 2021 that investigated the treatment effects of SC-EVs in a rodent ischemic stroke model. Infarct volume was the primary outcome. Neurological severity scores (mNSS) were the secondary outcome. The standard mean difference (SMD) and the confidence interval (CI) were calculated using a random-effects model. R and Stata 15.1 were used to conduct the meta-analysis. Results Twenty-one studies published from 2015 to 2021 met the inclusion criteria. We also found that SCs-EVs reduced infarct volume by an SMD of − 2.05 (95% CI − 2.70, − 1.40; P

Abstract Background Recently, several rare variants of SPTLC1 were identified as disease cause for juvenile amyotrophic lateral sclerosis (ALS) by disrupting the normal homeostatic regulation of serine palmitoyltransferase (SPT). However, further exploration of the rare variants in large cohorts was still necessary. Meanwhile, SPTLC2 plays a similar role as SPTLC1 in the SPT function. Methods To explore the genetic role of SPTLC1 and SPTLC2 in ALS, we analyzed the rare protein-coding variants in 2011 patients with ALS and 3298 controls from the Chinese population with whole exome sequencing. Fisher’s exact test was performed between each variant and disease risk, while at gene level over-representation of rare variants in patients was examined with optimized sequence kernel association test (SKAT-O). Results Totally 33 rare variants with minor allele frequency

Objectives: The Lateral Arm Free Flap (LAFF) offers advantageous features like variable thickness and minimal hair growth. LAFF is primarily used in orofacial and pharyngeal reconstructions, with limited reports on tracheal/esophageal applications. Also, the psychological prognosis and quality of life in patients with LAFF reconstruction are lacking. Methods: This retrospective case series presents outcomes of LAFF reconstruction for head and neck surgical defects which included 19 patients. The disease type, location of reconstruction, TNM staging, tumor size, chemoradiation status, anxiety, depression, quality of life and detailed perioperative information of the LAFF reconstruction surgery were presented in a descriptive pattern. Subgroup analysis was conducted using Mann–Whitney U and Pearson r test. Results: All 19 patients (100%) had a viable flap after surgery with 5 (26.3%) of them developed flap-related complication. Patients with oropharyngeal reconstruction were more likely to have lower anxiety and depression score and higher quality of life than those with below-oropharyngeal reconstruction. However, no significant p-value was generated in any subgroup comparison or correlation test. And the application of LAFF in esophageal and tracheal reconstruction was proved to be successful. Conclusions: The lateral arm free flap exhibits remarkable versatility and multifunctionality, providing advantageous outcomes in head and neck reconstruction. Level of evidence: Level 4 according to OCEBM.

Purpose Numerous indicators can be used to predict tumor patients’ prognosis and tumor regression grade (TRG). The role of the neutrophil-lymphocyte ratio (NLR) among individuals with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) hasn't been studied, nevertheless. This study aims to explore the predictive value of the NLR before nCRT (pre-NLR) in TRG and prognosis of LARC patients undergoing nCRT.. Methods In this retrospective investigation, 326 LARC patients receiving nCRT in total were included. The link between the pre-NLR and TRG was examined using a logistic regression analysis. A Cox-based nomogram was created in the meanwhile to forecast overall survival (OS). With the use of calibration plots and receiver operating characteristic (ROC) curves, we evaluated the nomogram's predictive capabilities. Results The median pre-NLR across 326 patients was 2.2 (interquartile range, IQR: 1.7-2.7). In the logistic regression analysis, only the pre-NLR for TRG in LARC patients receiving nCRT was statistically significant (odds ratio, OR = 0.62, 95% CI: 0.47-0.80, P

Abstract CO impurity‐induced catalyst deactivation has long been one of the biggest challenges in proton‐exchange membrane fuel cells, with the poisoning phenomenon mainly attributed to the overly strong adsorption on the catalytic site. Here, we present a mechanistic study that overturns this understanding by using Rh‐based single‐atom catalysis centers as model catalysts. We precisely modulated the chelation structure of the Rh catalyst by coordinating Rh with C or N atoms, and probed the reaction mechanism by surface‐enhanced Raman spectroscopy. Direct spectroscopic evidence for intermediates indicates that the reactivity of adsorbed OH*, rather than the adsorption strength of CO*, dictates the CO electrocatalytic oxidation behavior. The RhN4 sites, which adsorb the OH* intermediate more weakly than RhC4 sites, showed prominent CO oxidation activity that not only far exceeded the traditional Pt/C but also the RhC4 sites with similar CO adsorption strength. From this study, it is clear that a paradigm shift in future research should be considered to rationally design high‐performance CO electro‐oxidation reaction catalysts by sufficiently considering the water‐related reaction intermediate during catalysis.

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

Accurate prediction of nucleic binding residues is essential for the understanding of transcription and translation processes. Integration of feature- and template-based strategies could improve the prediction of these key residues in proteins. Nevertheless, traditional hybrid algorithms have been surpassed by recently developed deep learning-based methods, and the possibility of integrating deep learning- and template-based approaches to improve performance remains to be explored. To address these issues, we developed a novel structure-based integrative algorithm called NABind that can accurately predict DNA- and RNA-binding residues. A deep learning module was built based on the diversified sequence and structural descriptors and edge aggregated graph attention networks, while a template module was constructed by transforming the alignments between the query and its multiple templates into features for supervised learning. Furthermore, the stacking strategy was adopted to integrate the above two modules for improving prediction performance. Finally, a post-processing module dependent on the random walk algorithm was proposed to further correct the integrative predictions. Extensive evaluations indicated that our approach could not only achieve excellent performance on both native and predicted structures but also outperformed existing hybrid algorithms and recent deep learning methods. The NABind server is available at http://liulab.hzau.edu.cn/NABind/.

Scalable synthesis of stable Cu clusters for heterogeneous catalysis is still a major challenge. Here the authors report a low-temperature atomic diffusion approach for synthesis of stable Cu cluster catalysts, which exhibit high yield of intermediate product in consecutive hydrogenation reactions.

The poor stability of ruthenium-based catalysts has greatly hampered their application in polymer electrolyte membrane water electrolysis. Here, the authors uncover the decisive role of reaction route on catalytic performance, which enables the screening of efficient ruthenium-based water oxidation catalysts.

Abstract Background Schizophrenia (SCZ) is a chronic and severe mental illness with no cure so far. Mendelian randomization (MR) is a genetic method widely used to explore etiologies of complex traits. In the current study, we aimed to identify novel proteins underlying SCZ with a systematic analytical approach. Methods We integrated protein quantitative trait loci (pQTLs) of the brain, cerebrospinal fluid (CSF), and plasma with the latest and largest SCZ genome-wide association study (GWAS) via a systematic analytical framework, including two-sample MR analysis, Steiger filtering analysis, and Bayesian colocalization analysis. Results The genetically determined protein level of C4A/C4B (OR = 0.70, p = 1.66E−07) in the brain and ACP5 (OR = 0.42, p = 3.73E−05), CNTN2 (OR = 0.62, p = 2.57E−04), and PLA2G7 (OR = 0.71, p = 1.48E−04) in the CSF was associated with a lower risk of SCZ, while the genetically determined protein level of TIE1 (OR = 3.46, p = 4.76E−05), BCL6 (OR = 3.63, p = 1.59E−07), and MICB (OR = 4.49, p = 2.31E−11) in the CSF were associated with an increased risk for SCZ. Pathway enrichment analysis indicated that genetically determined proteins suggestively associated with SCZ were enriched in the biological process of the immune response. Conclusion In conclusion, we identified one protein in the brain and six proteins in the CSF that showed supporting evidence of being potentially associated with SCZ, which could provide insights into future mechanistic studies to find new treatments for the disease. Our results also supported the important role of neuroinflammation in the pathogenesis of SCZ.

Background Immunoglobulin A nephropathy (IgAN) has been well studied among young people, but few data on clinicopathological characteristics, treatment response and outcomes for elderly IgAN patients are available.Methods A cohort study of elderly IgAN patients was performed. The combined endpoints of renal outcome were a 50% decline in eGFR compared with the time of renal biopsy, end-stage kidney disease and/or death. Risk factors associated with poor renal outcomes were then determined. The benefits of immunosuppressant therapies were also evaluated by Kaplan-Meier survival curve analysis.Results This study ultimately included 126 elderly patients with IgAN. Comparison between the endpoint and non-endpoint groups indicated that patients with poor outcomes had more severe clinical features, such as worse kidney function, severe hematuria and lower albumin levels. Cox regression analysis indicated that age (HR 1.15, 95% CI 1.02–1.29, p = 0.021), male gender (HR 9.71, 95% CI 1.00–97.56, p = 0.050), and urine red blood cells (HR 1.003, 95% CI 1.000–1.006, p = 0.029) were independent risk factors for poor renal outcome in elderly IgAN patients. To explore possible reasons accounting for the predictive value of age and sex, patients were divided into two groups based on these two variables. Patients in the geriatric group had lower serum albumin, estimated glomerular filtration rate, hemoglobin and aspartate aminotransferase levels than those in the quinquagenarian group. Male patients tended to have higher hemoglobin, higher alanine aminotransferase, and lower triglycerides and cholesterol levels than female patients. To investigate different treatment responses, patients were classified into two groups depending on treatment strategies (renin-angiotensin system inhibitors and immunosuppressive therapy), and the survival analysis indicated no significant difference in kidney outcome between the two groups (p > 0.05). This result still holds after adjusting for age, sex, eGFR, hematuria, and proteinuria.Conclusion Advanced age, male, and hematuria might be independently associated with poor kidney outcomes in elderly patients with IgAN. Immunosuppressive therapy might confer no overall benefit to older IgAN patients.

Photodynamic therapy has emerged as a recognized anti-tumor treatment involving three fundamental elements: photosensitizers, light, and reactive oxygen species. Enhancing the effectiveness of photosensitizers remains the primary avenue for improving the biological therapeutic outcomes of PDT. Through three generations of development, HPPH is a 2-(1-hexyloxyethyl)-2-devinyl derivative of pyropheophorbide-α, representing a second-generation photosensitizer already undergoing clinical trials for various tumors. The evolution toward third-generation photosensitizers based on HPPH involves structural modifications for multimodal applications and the combination of multifunctional compounds, leading to improved imaging localization and superior anti-tumor effects. While research into third-generation HPPH is beneficial for advancing PDT treatment, equal attention should also be directed toward the other two essential elements and personalized diagnosis and treatment methodologies.

Abstract The electrochemical carbon dioxide reduction reaction (CO2RR) for high‐value‐added products is a promising strategy to tackle excessive CO2 emissions. However, the activity of and selectivity for catalysts for CO2RR still need to be improved because of the competing reaction (hydrogen evolution reaction). In this study, for the first time, we have demonstrated dual atomic catalytic sites for CO2RR from a core–shell hybrid of the covalent–organic framework and the metal–organic framework. Due to abundant dual atomic sites (with CoN4O and ZnN4 of 2.47 and 11.05 wt.%, respectively) on hollow carbon, the catalyst promoted catalysis of CO2RR, with the highest Faradic efficiency for CO of 92.6% at –0.8 V and a turnover frequency value of 1370.24 h–1 at –1.0 V. More importantly, the activity and selectivity of the catalyst were well retained for 30 h. The theoretical calculation further revealed that CoN4O was the main site for CO2RR, and the activity of and selectivity for Zn sites were also improved because of the synergetic roles.

The preferential oxidation of CO (PROX) in hydrogen is a promising solution for hydrogen purification. Here the authors report a novel bimetallic Pt-Fe catalyst with ultralow metal loading which delivers excellent catalytic activity and selectivity in PROX, while maintains good stability for a long period.

A new quick-scanning extended X-ray absorption fine-structure (QEXAFS) system for in situ studies has been developed and tested on the general XAFS beamline at the Shanghai Synchrotron Radiation Facility. In the new system, an analog-to-digital converter (ADC) with 1 MHz sampling rate is used to acquire the detector data while one scaler is used to precisely calculate the scanning energy. Two external hardware trigger signals were adopted to synchronize the data collection of the ADC and the scaler. The software development platforms of the double-crystal monochromator control system and the new QEXAFS system have been unified with the Experimental Physics and Industrial Control System. By comparing the spectra acquired by the conventional step-by-step XAFS system with an energy range of 1200 eV at the 7.5um Cu foil K-edge, the new system demonstrates satisfactory signal-to-noise ratio and energy resolution. The previous shortcomings, including distortion of the spectrum and energy shift, have been overcome. The tests with different integration times indicated that appropriate parameters not only ensure good experimental results but also enhance the smoothness of the XAFS spectrum at high energy zones. The reliability of the new system has also been verified.

Abstract Increased expression of CD33 in the brain has been suggested to be associated with increased amyloid plaque burden, while the peripheral level of CD33 in Alzheimer’s disease (AD) patients and its role in AD remain unclear. The current study aimed to systematically explore the bidirectional relationship between peripheral CD33 and AD. Genome-wide association study (GWAS) datasets of AD (Ncases: 21982; Ncontrols: 41944), blood CD33 mRNA level, the plasma CD33 protein level, and CD33 expression on immune-cell subtypes were obtained from GWASs conducted in the European population. Eligible IVs were extracted from the GWASs. MR estimates were calculated by inverse-variance weighting (IVW) and other sensitivity analyses. The main statistical analyses were conducted using TwoSampleMR (v.0.5.5) in R package (V.4.1.2).In the forward MR analysis (CD33 as exposure and AD as outcome), the IVW results indicated that elevated blood CD33 mRNA level (OR [95% CI] = 1.156[1.080, 1.238], p = 3.25e-05), elevated serum CD33 protein level (OR [95% CI] = 1.08 [1.031, 1.139], p = 1.6e-03) and increased CD33's expression on immune cell subtypes (p 0.05). In conclusion, our results indicated that elevated peripheral expression of CD33 was causal to the development of AD. Future studies are needed to work on developing CD33 as a biomarker and therapeutic target in AD.

Zhong et al report sodium-promoted metallic Ru nanoparticles for the direct production of olefins from syngas with ultrahigh carbon efficiency where the total selectivity of undesired CH4 and CO2 is suppressed to only 5% for over 500 hours on stream.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Quantitatively describing the atomic configuration of the catalytically active sites is challenging. Here the authors demonstrate that tuning crystal-phase of metal single-particle enables to precisely describe the atomic structure of the active sites and accurately identify the activation routes of the reacting molecules.

Abstract Background Recently, a few studies have indicated a relationship between the gut microbiota and IgA nephropathy (IgAN). Whether the gut microbiota participates in the pathogenesis of IgAN and whether probiotics are effective in treating IgAN are still controversial. Therefore, this study aimed to identify the differences in the structure of the gut microbiota between IgAN and controls and to evaluate the efficacy and mechanism of probiotics in the treatment of IgAN. Methods To address this question, 35 IgAN patients and 25 healthy volunteers were enrolled, and a mouse IgAN model was also constructed. The stool microbes were analyzed by 16S rRNA high-throughput sequencing to identify the differential strains between IgAN and healthy controls. The impact of probiotics on the structure of the intestinal flora and the efficacy of the probiotics in the treatment of IgAN were evaluated. Results Although the microflora structure of mice and humans was not the same, both patients and mice with IgAN exhibited gut microbiota dysbiosis, with all subjects presenting an evident decrease in Bifidobacterium levels. The Bifidobacterium proportion was negatively correlated with proteinuria and hematuria levels, indicating that the decreased Bifidobacterium abundance could be related to IgAN severity. Probiotic treatment containing Bifidobacterium in IgAN mice could significantly alleviate gut dysbiosis, specifically by increasing the proportion of beneficial bacteria and reducing the abundance of potentially pathogenic bacteria. Moreover, both probiotics and their metabolites, short-chain fatty acids (SCFAs), could attenuate IgAN clinicopathological manifestations by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Conclusions Supplementation with probiotics mainly containing Bifidobacterium could markedly improve gut dysbiosis in IgAN. Moreover, both probiotics and their SCFA metabolites could attenuate the clinicopathological manifestations of IgAN by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Therefore, probiotics have potential as an adjunctive therapy for IgAN.

Traditional approaches for transition-metal catalyzed oxidative cross-coupling reactions rely on sp 2-hybridized starting materials. Here the authors report a heterogeneous Pd-catalyzed radical relay method for the conversion of a heteroarene C(sp 3)–H bond into ethers.

Abstract Background The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS. Methods The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646. Results A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS. Conclusions Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.

Carbon dioxide electroreduction driven by renewable electricity into high‐value chemicals enables energy storage while contributing to climate change mitigation. Herein, a CuPd bimetallic catalyst is developed by electrodeposition for efficient CO2 electroreduction, achieving a C2+ Faradaic efficiency as high as 75.6% with a current density of −200 mA cm−2 at −1.15 V versus reversible hydrogen electrode. Upon incorporation of Pd, the average d‐band center of the CuPd bimetallic catalyst downward shifts relative to the Fermi level, making the adsorbed CO intermediates active for further C–C coupling. Theoretical calculations confirm that CO generated on the Pd domain can spill over to the CuPd interface for C–C coupling with a lower energy barrier, further promoting the formation of C2+ compounds. This study provides insights into the rational design of Cu‐based bimetallic catalysts for highly efficient CO2 electroreduction to multicarbon products.

Platinum (Pt)‐based catalysts are considered as the most active catalysts for the oxygen reduction reaction (ORR). However, their applications have remained limited because of the high cost of Pt, and developing catalysts with low Pt contents is a challenge. Herein, a highly active catalyst (Pt–COF800) is constructed for the ORR by immobilizing hierarchical Pt subnano‐ and nanoparticles on covalent organic framework (COF)‐derived carbon. The catalyst shows excellent activity in alkaline conditions. The physical characterization demonstrates low nuclear Pt atoms and nanoparticles and confirms the role of heterogeneous active sites. This work paves the way for the construction of functional porous carbon materials with dual‐scale Pt clusters and may be applied to industrial catalytic reactions.

BackgroundIn the information era, patients can easily be misled by inaccurate internet content, thus making not well-informed decisions about medical issues. Adenoid hypertrophy, one of the most common causes of chronic upper airway obstruction in children and adolescents, may lead to serious complications, including sleep apnea and craniofacial change. There have been no critical studies about the quality of websites on adenoid hypertrophy, posing a challenge for users without a medical background to determine which website offers more reliable information. Moreover, the blockage of access to internet search tools such as Google, Yahoo, and others has created an isolated internet environment for the enormous user population in mainland China. Differences in internet legislation, the commercial environment, and culture are also likely to result in varied quality of online health information inside and outside mainland China. To date, no study has compared the quality difference between mainland Chinese and English websites. ObjectiveThe aims of this study were to (1) analyze the quality of websites about adenoid hypertrophy accessible by patients, (2) investigate the quality differences between Chinese and English websites, (3) determine which type of website (eg, government-sponsored, health care provider) is more reliable in terms of medical information, and (4) determine whether the blockage of foreign websites is hindering users’ accessibility to better-quality websites in mainland China. MethodsThe first 100 websites (excluding advertisements) displayed on the top three search engines worldwide and in mainland China for the key search term “enlarged adenoids” were collected as the data source. The websites were evaluated based on accessibility, accountability, interactivity, structure, and content quality (accuracy, content coverage, and objectivity). Cohen κ was calculated, and one-way ANOVA and the Kruskal-Wallis test were performed to compare the results between groups and subgroups. ResultsThe mean score for the content quality of English websites was significantly higher than that of Chinese websites (6.16 vs 4.94, P=.03 for Google, Bing, and Yahoo; 6.16 vs 4.16, P