Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Outcomes, responses, and prognostic analyses of intrathecal combined treatment for leptomeningeal metastasis from lung adenocarcinoma.

BACKGROUND: Leptomeningeal metastasis (LM) is a severe lung cancer complication, with potentially fatal consequences. The use of intrathecal therapy (IT) combined with systemic therapy has shown promise as a treatment approach for LM. Thus, this study aimed to evaluate the features and responses to IT combined therapy and identify determinants affecting patients with leptomeningeal metastasis resulting from lung adenocarcinoma (LM-LA). METHODS: A retrospective analysis of medical records from our hospital database was performed, covering from April 2018 to August 2022, for 37 patients diagnosed with LM-LA and treated with IT combined therapy. Patients who received IT combined therapy for LM-LA were evaluated for demographic characteristics, treatment efficacy, survival, and variables that impacted them. RESULTS: The median overall survival (mOS) of 37 patients was 16.0 months, and the survival rates at 6 and 12 months were 75.7% and 35.1%, respectively. Among the 21 patients with LM-LA who received IT combined with tyrosine kinase inhibitors (TKIs), the mOS was 17.0 months, which was significantly longer than that of patients treated with IT combined with chemotherapy (7.0 months, P = 0.010) and the best supportive care (6.0 months, P = 0.001). However, no significant survival benefit was observed in patients treated with IT combined with TKIs when compared with those treated with IT combined with PD-1 (5.0 months, P = 0.249). Multivariate analysis indicated that the combination of TKIs was an independent favorable prognostic factor for patients with LM-LA. CONCLUSION: Combination treatment is regarded as an additional option for patients with LM-LA. Compared with other combination therapies in our study, IT combined with TKI therapy provided a better survival outcome for patients with LM-LA.

Photosensitizer-loaded hydrogels: A new antibacterial dressing.

Bacterial wound infection has emerged as a pivotal threat to human health worldwide, and the situation has worsened owing to the gradual increase in antibiotic-resistant bacteria caused by the improper use of antibiotics. To reduce the use of antibiotics and avoid the increase in antibiotic-resistant bacteria, researchers are increasingly paying attention to  photodynamic therapy, which uses light to produce reactive oxygen species to kill bacteria. Treating bacteria-infected wounds by photodynamic therapy requires fixing the photosensitizer (PS) at the wound site and maintaining a certain level of wound humidity. Hydrogels are materials with a high water content and are well suited for fixing PSs at wound sites for antibacterial photodynamic therapy. Therefore, hydrogels are often loaded with PSs for treating bacteria-infected wounds via antibacterial photodynamic therapy. In this review, we systematically summarised the antibacterial mechanisms and applications of PS-loaded hydrogels for treating bacteria-infected wounds via photodynamic therapy. In addition, the recent  studies and the research status progresses of novel antibacterial hydrogels are discussed. Finally, the challenges and future prospects of PS-loaded hydrogels are reviewed.

Centriolar appendages evolve into the inner sheath of mammalian flagella.

The annulus, a septin-based structure in vertebrate sperm connecting the MP and PP, has unclear migration mechanics. In this issue, Hoque et al. (https://doi.org/10.1083/jcb.202307147) report that the CBY3/CIBAR1 complex ensures its precise positioning by regulating membrane properties.

Preoperative supine time for adrenal venous sampling: a prospective randomized controlled trial.

BACKGROUND: Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17-23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. METHODS/DESIGN: This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). DISCUSSION: P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.

Double-edged effect of frequent freeze-thaw on the stability of zero-valent iron after heavy metal remediation.

Freeze-thaw cycles (FTCs) cause dynamic microscale changes in ions and solvents. During freezing, heavy metals adsorbed on zero-valent iron (M-ZVI) and protons are excluded by ice crystals and concentrated in the liquid-like grain boundary region. The high proton concentration in this region leads to the dissolution of the passivation layer of ZVI. To assess the environmental risks of M-ZVI during FTCs, this study evaluated the stability of M-ZVI in this scenario from both microscale and macroscale perspectives. The results showed that the dissolution of the passivation layer had a dual effect on the stability of M-ZVI, which depends on the by-products of M-ZVI. The dissolution of the passivation layer was accompanied by the leaching of heavy metals, such as Ni-ZVI, but it also enhanced the reactivity of ZVI, causing it to re-react with desorbed heavy metals. The stability of Cr-ZVI and Cd-ZVI was improved due to frequent FTCs. Furthermore, changes in the surrounding environment (water dipole moment, ion concentration, etc.) of ZVI affected the crystallization of Fe oxides, increasing the content of amorphous Fe oxide. As low-crystallinity Fe oxides could facilitate ion doping, Ni2+ was doped into Fe3O4 lattice during FTCs, which reduced the mobility of heavy metals. Contrary to traditional views that freezing temperatures slow chemical reactions, this study provides new insights into the application of iron-based materials in cold environments.

Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a permanent, asymptomatic segmental dilatation of the abdominal aorta, with a high mortality risk upon rupture. Identification of potential key genes and pathways may help to develop curative drugs for AAA. We conducted RNA-seq on abdominal aortic tissues from both AAA patients and normal individuals as a control group. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential key genes and pathways. A total of 1148 differential expressed genes (DEGs) (631 up-regulated and 517 down-regulated) were identified in our study. Gene Ontology (GO) analysis revealed enrichment in terms related to extracellular matrix organization, while KEGG analysis indicated enrichment in hematopoietic cell lineage and ECM-receptor interaction. Protein-protein interaction (PPI) network analysis revealed several candidate key genes, and differential expression of 6 key genes (CXCL8, CCL2, PTGS2, SELL, CCR7, and CXCL1) was validated by Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic curve (ROC) analysis demonstrated these genes' high discriminatory ability between AAA and normal tissues. Immunohistochemistry indicated that several key genes were highly expressed in AAA tissues. Single-cell RNA sequencing revealed differential distribution patterns of these identified key genes among various cell types. 26 potential drugs linked to our key genes were found through DGIdb. Overall, our study provides a comprehensive evaluation of potential key genes and pathways in AAA, which could pave the way for the development of curative pharmacological therapies.

Efficient electrocatalytic oxygen reduction reaction of thermally optimized carbon black supported zeolitic imidazolate framework nanocrystals under low-temperature.

Turning commercially available low-cost conducting carbon black materials into functional electrocatalytic electrode media using simple surface chemical modification is a highly attractive approach. This study reports on remarkably enhanced oxygen electrocatalytic activity of commercially available Ketjenblack (KB) by growing a non-precious cobalt metal-based zeolitic-imidazolate framework (ZIF-67) at room temperature in methanol solution followed by a mild thermolysis. The resulting Co@CoOx nanoparticle decorated nitrogen-doped KB derived from the optimized ZIF-67 : KB weight ratio of hybrid samples at 500-600 °C shows high performance for the oxygen reduction reaction (ORR) with impressive Eonset and E1/2 values of ∼0.90 and ∼0.83 V (vs. RHE), respectively in 0.1 M KOH electrolyte. Such ORR activity is comparable to, or better than many metal@metal-oxide-carbon based electrocatalysts synthesized under elevated carbothermal temperatures and using multicomponent/multistep chemical modification conditions. Therefore, a simple electrocatalyst design reported in this work is an efficient synthesis route that not only utilises earth-abundant carbon black but also comprises scalable room temperature synthesized ZIF-67 following mild thermolysis conditions under 600 °C.

How Do Heterogeneous Networks Affect a Firm's Innovation Performance? A Research Analysis Based on Clustering and Classification.

Based on authorized patents of China's artificial intelligence industry from 2013 to 2022, this paper constructs an Industry-University-Research institution (IUR) collaboration network and an Inter-Firm (IF) collaboration network and used the entropy weight method to take both the quantity and quality of patents into account to calculate the innovation performance of firms. Through the hierarchical clustering algorithm and classification and regression trees (CART) algorithm, in-depth analysis has been conducted on the intricate non-linear influence mechanisms between multiple variables and a firm's innovation performance. The findings indicate the following: (1) Based on the network centrality (NC), structural hole (SH), collaboration breadth (CB), and collaboration depth (CD) of both IUR and IF collaboration networks, two types of focal firms are identified. (2) For different types of focal firms, the combinations of network characteristics affecting their innovation performance are various. (3) In the IUR collaboration network, focal firms with a wide range of heterogeneous collaborative partners can obtain high innovation performance. However, focal firms in the IF collaboration network can achieve the same aim by maintaining deep collaboration with other focal firms. This paper not only helps firms make scientific decisions for development but also provides valuable suggestions for government policymakers.

Target-Site and Metabolic Resistance Mechanisms to Penoxsulam in Late Watergrass (Echinochloa phyllopogon) in China.

Echinochloa phyllopogon, a malignant weed in Northeast China's paddy fields, is currently presenting escalating resistance concerns. Our study centered on the HJHL-715 E. phyllopogon population, which showed heightened resistance to penoxsulam, through a whole-plant bioassay. Pretreatment with a P450 inhibitor malathion significantly increased penoxsulam sensitivity in resistant plants. In order to determine the resistance mechanism of the resistant population, we purified the resistant population from individual plants and isolated target-site resistance (TSR) and nontarget-site resistance (NTSR) materials. Pro-197-Thr and Trp-574-Leu mutations in acetolactate synthase (ALS) 1 and ALS2 of the resistant population drove reduced sensitivity of penoxsulam to the target-site ALS, the primary resistance mechanisms. To fully understand the NTSR mechanism, NTSR materials were investigated by using RNA-sequencing (RNA-seq) combined with a reference genome. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis further supported the enhanced penoxsulam metabolism in NTSR materials. Gene expression data and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation confirmed 29 overexpressed genes under penoxsulam treatment, with 16 genes concurrently upregulated with quinclorac and metamifop treatment. Overall, our study confirmed coexisting TSR and NTSR mechanisms in E. phyllopogon's resistance to ALS inhibitors.

ALA-PDT shortens the course of antibiotic therapy for skin infection caused by Mycobacterium marinum.

BACKGROUND: Recently, the number of cases of Mycobacterium marinum infection has increased. Due to the nonspecific clinical manifestations and lack of standardized treatment guidelines, these infections are often misdiagnosed and are challenging to treat. METHODS: In this study, four patients had M. marinum skin infections accompanied by a high-risk exposure history and were diagnosed by bacterial culture and gene chip. Two patients were treated with antibiotic therapy alone, and the other two patients were treated with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics. RESULTS: All four patients enrolled in the study were cured with 100 % efficacy. Two patients were cured after receiving two active antibiotics for 4 months. The other two patients, having considered the drug resistance and intolerance described above, were cured after receiving two active antibiotics for 1-1.5 months along with combination therapy with ALA-PDT. CONCLUSION: Combination therapy with ALA-PDT and antibiotics was chosen to shorten the duration of antibiotic treatment and reduce the occurrence of adverse reactions.

Warburg effect-related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma.

BACKGROUND: Glioblastoma (GBM), the most common primary malignant brain tumor, has a poor prognosis, with a median survival of only 14.6 months. The Warburg effect is an abnormal energy metabolism, which is the main cause of the acidic tumor microenvironment. This study explored the role of the Warburg effect in the prognosis and immune microenvironment of GBM. METHODS: A prognostic risk score model of Warburg effect-related genes (Warburg effect signature) was constructed using GBM cohort data from The Cancer Genome Atlas. Cox analysis was performed to identify independent prognostic factors. Next, the nomogram was built to predict the prognosis for GBM patients. Finally, the drug sensitivity analysis was utilized to find the drugs that specifically target Warburg effect-related genes. RESULTS: Age, radiotherapy, chemotherapy, and WRGs score were confirmed as independent prognostic factors for GBM by Cox analyses. The C-index (0.633 for the training set and 0.696 for the validation set) and area under curve (>0.7) indicated that the nomogram exhibited excellent performance. The calibration curve also indicates excellent consistency of the nomogram between predictions and actual observations. In addition, immune microenvironment analysis revealed that patients with high WRGs scores had high immunosuppressive scores, a high abundance of immunosuppressive cells, and a low response to immunotherapy. The Cell Counting Kit-8 assays showed that the drugs targeting Warburg effect-related genes could inhibit the GBM cells growth in vitro. CONCLUSION: Our research showed that the Warburg effect is connected with the prognosis and immune microenvironment of GBM. Therefore, targeting Warburg effect-related genes may provide novel therapeutic options.

A Knowledge Map of the Relationship between Diabetes and Stroke: A Bibliometric Analysis Study.

INTRODUCTION: The correlation between diabetes and stroke has been studied extensively in epidemiological research. Here we used bibliometric software to visualize and analyze the literature related to diabetic stroke to provide an overview of the current state of research, hot spots, and future trends in the field. METHODS: Based on the Web of Science Core Collection(WoSCC) database, we collected studies related to diabetic stroke from 2007 to May 2022. We used CiteSpace (version 6.1.R5), VOSviewer, and Sci-mago Graphica to create knowledge maps and conduct visual analyses on authors, countries, in-stitutions, cited references, and keywords, and Origin for statistical analysis. RESULTS: We included a total of 5171 papers on diabetic stroke from the WoSCC database. Overall, there was a steady increase in the number of publications, with a high number of emerging scientists. The United States was the most productive and influential country, which dominated national col-laborations. The most common subject category was "neurology". In total, 12 major clusters were generated from the cited references. Keywords analysis showed that keywords related to post-stroke injury and treatment are those with the highest burst intensity and latest burst time. CONCLUSIONS: Individual disease treatment remains a hot topic and how to balance acute stroke treatment and glycemic control is currently a difficult clinical problem. At the same time, the mechanism of their interaction and the prevention and treatment of related causative factors remain a hot topic of current and future research.

Improved Harmony Search Algorithm for Enhancing Efficiency and Quality in Optimization of the Distillation Process.

Reducing production costs is one of the main objectives of process intensification; in this work, production costs of the distillation process are reduced by reducing equipment size and utility consumption from the perspective of process optimization to achieve the purpose of process intensification. The application of intelligent optimization algorithms in the optimization process of distillation is vital to achieving high efficiency and low costs. Combining the harmony search algorithm with the characteristics of distillation optimization, a new distillation harmony search algorithm (DHSA) was proposed, which includes the self-adaptive adjustment of parameters, roulette selection strategy, and ratio optimization strategy. Benefiting from the DHSA, the optimal total annual cost and calculation times were remarkably reduced when compared with reported algorithms in the optimization of four distillation cases including the two-column model, three-column model, reactive distillation column model, and dividing-wall extractive distillation column model. In addition, the highest coefficient of variation of DHSA in 10 parallel calculations is 1.25%. These results indicate that DHSA has the advantages of a higher-quality solution, less computing time, and higher stability, which not only improves the optimization efficiency and quality but also inspires the optimization strategies for other algorithms.

The soil pore structure encountered by roots affects plant-derived carbon inputs and fate.

Plant roots are the main supplier of carbon (C) to the soil, the largest terrestrial C reservoir. Soil pore structure drives root growth, yet how it affects belowground C inputs remains a critical knowledge gap. By combining X-ray computed tomography with 14 C plant labelling, we identified root-soil contact as a previously unrecognised influence on belowground plant C allocations and on the fate of plant-derived C in the soil. Greater contact with the surrounding soil, when the growing root encounters a pore structure dominated by small (< 40 µm Ø) pores, results in strong rhizodeposition but in areas of high microbial activity. The root system of Rudbeckia hirta revealed high plasticity and thus maintained high root-soil contact. This led to greater C inputs across a wide range of soil pore structures. The root-soil contact Panicum virgatum, a promising bioenergy feedstock crop, was sensitive to the encountered structure. Pore structure built by a polyculture, for example, restored prairie, can be particularly effective in promoting lateral root growth and thus root-soil contact and associated C benefits. The findings suggest that the interaction of pore structure with roots is an important, previously unrecognised, stimulus of soil C gains.

Antithrombin III deficiency in a patient with recurrent venous thromboembolism: A case report.

BACKGROUND: Antithrombin III (AT3) deficiency, an autosomal dominant disease, increases the likelihood of an individual developing venous thromboembolism (VTE). Long-term anticoagulation treatment is required for those suffering from AT3 deficiency. CASE SUMMARY: A man aged 23, who had a history of deep venous thrombosis (DVT), experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban. He was diagnosed with DVT and antithrombin III deficiency as genetic testing revealed a single nucleotide variant in SERPINC1 (c.667T>C, p.S223P). The patient was advised to accept long-term anticoagulant therapy. CONCLUSION: Inherited AT3 deficiency due to SERPINC1 mutations results in recurrent VTE. Patients may benefit from long-term anticoagulant therapy.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry. / 基于巯基-çƒ¯ç‚¹å‡»åŒ–å­¦åˆ¶å¤‡ä¸ç´ è›‹ç™½/é€æ˜Žè´¨é ¸å¤åˆæ°´å‡èƒ¶.

OBJECTIVES: To design and prepare silk fibroin/hyaluronic acid composite hydrogel. METHODS: The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope. RESULTS: The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good. CONCLUSIONS: The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.