Search

Abstract Background Spiroplasma eriocheiris has been proved to be a pathogen causing tremor disease of Eriocheir sinensis, it is also infectious to other aquatic crustaceans, resulting in a serious threat on the sustainable development of the aquaculture industry. S. eriocheiris is a helical-shaped microbe without a cell wall, and its motility is related to the cytoskeleton protein MreB which belongs to the actin superfamily and has five MreB homologs. Results In this study, we purified MreB3, MreB4 and MreB5, and successfully prepared monoclonal antibodies. After S. eriocheiris treated with actin stabilizator Phalloidin and inhibitors A22, we found that Phalloidin and A22 affect the S. eriocheiris morphology by altering MreB expression. We confirmed that the ability of S. eriocheiris to invade E. sinensis was increased after treatment with Phalloidin, including that the morphology of E. sinensis blood lymphocytes was deteriorated, blood lymphocytes viability was decreased, peroxidase activity and cell necrosis were increased. On the contrary, the pathogenicity of S. eriocheiris decreased after treatment with A22. Conclusions Our findings suggest that the MreB protein in S. eriocheiris plays a crucial role in its morphology and pathogenicity, providing new insights into potential strategies for the prevention and control of S. eriocheiris infections.

Abstract Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis.

This study describes two new species within the genus Paranemachilus. Paranemachilus luegvetensis sp. nov. and Paranemachilus liui sp. nov. can be distinguished from all recognized congeners by a combination of morphological characteristics and substantial genetic divergences. Paranemachilus luegvetensis sp. nov. is characterized by scaled cheeks; the whole body covered in scales, except for the head; 11–12 branched pectoral fin rays; 4–5 preoperculomandibular canal pores; body depth 13.5%–16.8% of standard length; and preanus length 68.3%–73.9% of standard length. Paranemachilus liui sp. nov. is characterized by scaled cheeks; the whole body covered in scales except for the head; 11–13 branched pectoral fin rays; 11–15 supraorbital canal pores at the base of the anterior nostrils; 7–9 preoperculomandibular canal pores; preanus length 67.4%–74.3% of standard length; snout length 21.4%–28.7% of lateral head length.

Abstract The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases of the disease and progress under intense evolutionary pressures. Organ-specific metastasis relies on the formation of pre-metastatic niche (PMN), with diverse cell types and complex cell interactions contributing to this concept, adding a new dimension to the traditional metastasis cascade. Prior to metastatic dissemination, as orchestrators of PMN formation, primary tumor-derived extracellular vesicles prepare a fertile microenvironment for the settlement and colonization of circulating tumor cells at distant secondary sites, significantly impacting cancer progression and outcomes. Obviously, solely intervening in cancer metastatic sites passively after macrometastasis is often insufficient. Early prediction of metastasis and holistic, macro-level control represent the future directions in cancer therapy. This review emphasizes the dynamic and intricate systematic alterations that occur as cancer progresses, illustrates the immunological landscape of organ-specific PMN creation, and deepens understanding of treatment modalities pertinent to metastasis, thereby identifying some prognostic and predictive biomarkers favorable to early predict the occurrence of metastasis and design appropriate treatment combinations.

Soft tissue integration around titanium (Ti) implants is weaker than that around natural teeth, compromising long-term success of Ti implants. Carbon monoxide (CO) possesses distinctive therapeutic properties, rendering it as a highly promising candidate for enhancing STI. However, achieving controlled CO generation at the STI interface remains challenging. Herein, a controlled CO-releasing dual-function coating was constructed on Ti surfaces. Under near-infrared (NIR) irradiation, the designed surface could actively accelerate CO generation for antibiosis against both aerobic and anaerobic bacteria. More importantly, in the absence of NIR, the slow release of CO induces macrophage polarization from pro-inflammatory phenotype towards pro-regenerative phenotype. In a rat implantation model with induced infection, the designed surface effectively controlled the bacterial infection, alleviates accompanying inflammation and modulated immune microenvironment, leading to enhanced STI. Single-cell sequencing revealed that the coating alters the cytokine profile within the soft tissue, thereby influencing cellular functions. Differentially expressed genes in macrophages are highly enriched in the PIK3-Akt pathway. Furthermore, the cellular communication between fibroblasts and macrophages was significantly enhanced through the CXCL12/CXCL14/CXCR4 and CSF1-CSF1R ligand-receptor pair. These findings indicate that our coating showed an appealing prospect for enhancing STI around Ti implants, which would ultimately contribute to the improved long-term success of Ti implants.

Abstract The continuous generation of multi-omics and phenotype data is propelling advancements in precision oncology. UCSCXenaShiny was developed as an interactive tool for exploring thousands of cancer datasets available on UCSC Xena. However, its capacity for comprehensive and personalized pan-cancer data analysis is being challenged by the growing demands. Here, we introduce UCSCXenaShiny v2, a milestone update through a variety of improvements. Firstly, by integrating multidimensional data and implementing adaptable sample settings, we create a suite of robust TPC (TCGA, PCAWG, CCLE) analysis pipelines. These pipelines empower users to conduct in-depth analyses of correlation, comparison, and survival in three modes: Individual, Pan-cancer and Batch screen. Additionally, the tool includes download interfaces that enable users to access diverse data and outcomes, several features also facilitate the joint analysis of drug sensitivity and multi-omics of cancer cell lines. UCSCXenaShiny v2 is an open-source R package and a web application, freely accessible at https://github.com/openbiox/UCSCXenaShiny .

Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats. This finding led us to hypothesize that the administration of exogenous CST is an effective strategy to promote wound healing in patients with DUs. We herein successfully prepared CST-loaded pDMA-pEPEMA nanoparticles (CST@NPs) designed to exhibit localized, acid-responsive behavior for enhanced wound healing. These CST@NPs were sensitive to acidic environments, triggering the rapid release of CST. In vitro experiments showed that CST@NPs effectively alleviated oxidative stress and reduced apoptosis in human umbilical vein endothelial cells (HUVECs). Our findings further demonstrated that CST@NPs accelerated re-epithelialization of the wound, enhanced collagen deposition, and stimulated angiogenesis, while alleviating the local inflammatory response. Both in vivo and in vitro results indicate that CST@NPs possess precise and rapid response capabilities in acidic environments, ensuring effective CST release to promote diabetic wound healing. In summary, this acid-responsive nanoparticle system presents a highly efficient therapeutic strategy for the treatment of chronic diabetic wounds.

Abstract High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8+ T cells. Using IFN-γ production as a proxy for CD8+ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8+ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8+ T cells, we enabled selective expansion and enhanced persistence of transduced cells, while limiting their terminal differentiation and senescence. LMO4 overexpression promoted transcriptional programs regulating stemness, increasing the numbers of stem-like CD8+ memory T cells and enhancing their polyfunctionality and recall capacity. When tested in syngeneic and xenograft tumor models, LMO4 overexpression boosted CD8+ T cell antitumor immunity, resulting in enhanced tumor regression. Rather than directly modulating gene transcription, LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21, inducing the expression of target genes (Tcf7, Socs3, Junb, and Zfp36) crucial for memory responses. CRISPR/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4, thereby abrogating the therapeutic benefit of LMO4 overexpression. These results establish LMO4 overexpression as an effective strategy to boost CD8+ T cell stemness, providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

The Asian Cat Snake genus Boiga Fitzinger, 1826 includes 37 species, with high species diversity. Five species of Boiga have been recorded in China including B. multomaculata (Boie, 1827), B. kraepelini (Stejneger, 1902), B. cyanea (Duméril, Bibron & Duméril, 1854), B. guangxiensis (Wen, 1998) and B. siamensis (Nutaphand, 1971). Previously, the validity of the species Boiga stoliczkae (Wall, 1909) was controversial. B. stoliczkae was considered in synonymy with B. ochracea. Currently, the taxonomy of B. multomaculata and B. ochracea (Theobald, 1868) was revised so that B. multomaculata and B. ochracea actually represent a single species and B. stoliczkae was recognised as a valid species. B. stoliczkae was previously known to be found in the west from central Nepal through Darjeeling, Sikkim and Bhutan to Arunachal Pradesh and Assam in north-eastern India.One adult female specimen of the Asian Cat Snake was collected from Gyirong County, near the China-Nepal border, Tibet, China during fieldwork on August 2023. We compared morphology and mitochondrial DNA sequence data with all the species of the genus Boiga. Both datasets strongly supported referring the Chinese specimens to B. stoliczkae (Wall, 1909) due to the 21 mid-dorsal scale rows and the uncorrected p-distance (mitochondrial DNA gene cytochrome b) between this specimen and B. stoliczkae which is 1.7%. We further described morphological characters of the Chinese specimen in detail and compared these with the specimens that had been previously described. The dorsal ground colour of the Chinese specimen is dark brown, with a black stripe distributed almost evenly across the tail. This is a novel morph of the species B. stoliczkae. The newly-collected Chinese specimen expands the distribution of the species on the Himalaya range.

Abstract [Objective] In order to reveal the molecular mechanism of photosynthetic midday-depression broken by water spring, the effects of continuous spraying on mango leaves were studied by omics technology. This study can provide basis for further optimizing water management to achieve the best consequences, and will have theoretical significance in enhancing mango yield and quality by aligning with the national policy objectives of reducing fertilizer usage and improving efficiency. [Methods] Mango cultivar “Tainong No. 1” in Yuanjiang was used as material. The mango in the fruiting stage was sprayed by water for three times during the midday depression (12:30-14:10), 20 minutes each time, with no water spraying as the control. The leaves were collected for transcriptome sequencing analysis. GO and KEGG databases were used to analyze the differentially expressed genes (DEGs). Analysis of gene expression was conducted by using DESeq, with |log2αFC| >1 and P

Summary: Nucleotide-binding leucine-rich repeat (NLR) proteins contribute widely to plant immunity by regulating defense mechanisms through the elicitation of a hypersensitive response (HR). Here, we find that TaRACK1B (the receptor for activated C-kinase 1B) regulates wheat immune response against Chinese wheat mosaic virus (CWMV) infection. TaRACK1B recruits TaSGT1 and TaHSP90 to form the TaRACK1B-TaSGT1-TaHSP90 complex. This complex is essential for maintaining NLR proteins’ stability (TaRGA5-like and TaRGH1A-like) in order to control HR activation and inhibit viral infection. However, the cysteine-rich protein encoded by CWMV can disrupt TaRACK1B-TaSGT1-TaHSP90 complex formation, leading to the reduction of NLR-protein stability and suppression of HR activation, thus promoting CWMV infection. Interestingly, the 7K protein of wheat yellow mosaic virus also interferes with this antiviral immunity. Our findings show a shared viral counter-defense strategy whereby two soil-borne viruses may disrupt the TaRACK1B-TaSGT1-TaHSP90 complex, suppressing NLR-protein-mediated broad-spectrum antiviral immunity and promoting viral infection in wheat.

The chlorophyll content (CC) directly affects photosynthesis, growth, and yield. However, the genetic basis of CC is still unclear in maize (Zea mays L.). Here, we conducted a genome-wide association study using mixed linear model for CC of the fifth leaves at seedling stage (CCFSS) and the ear leaves at filling stage (CCEFS) for 334 maize inbred lines. The heritability estimates for CCFSS and CCEFS, obtained via variance components analysis using the lme4 package in R, were 70.84% and 78.99%, respectively, indicating that the CC of leaves is primarily controlled by genetic factors. A total of 15 CC-related SNPs and 177 candidate genes were identified with a p-value < 4.49 × 10−5, which explained 4.98–7.59% of the phenotypic variation. Lines with more favorable gene variants showed higher CC. Meanwhile, Gene Ontology (GO) analysis implied that these candidate genes were probably related to chlorophyll biosynthesis. In addition, gene-based association analyses revealed that six variants in GRMZM2G037152, GRMZM5G816561, GRMZM2G324462, and GRMZM2G064657 genes were significantly (p-value < 0.01) correlated with CC, of which GRMZM2G064657 (encodes a phosphate transporter protein) and GRMZM5G816561 (encodes a cytochrome P450 protein) were specifically highly expressed in leaves tissues. Interestingly, these candidate genes were previously reported to involve in the regulation of the contents of chlorophyll in plants or Chlamydomonas. These results may contribute to the understanding of genetic basis and molecular mechanisms of maize CC and the selection of maize varieties with improved CC.

Summary: Loss-of-function mutations in the C terminus of TPL2 kinase promote oncogenesis by impeding its proteasomal degradation, leading to sustained protein expression. However, the degradation mechanism for TPL2 has remained elusive. Through proximity-dependent biotin identification (BioID), we uncovered tripartite motif-containing 4 (TRIM4) as the E3 ligase that binds and degrades TPL2 by polyubiquitination of lysines 415 and 439. The naturally occurring TPL2 mutants R442H and E188K exhibit impaired TRIM4 binding, enhancing their stability. We further discovered that TRIM4 itself is stabilized by another E3 ligase, TRIM21, which in turn is regulated by KRAS. Mutant KRAS recruits RNF185 to degrade TRIM21 and subsequently TRIM4, thereby stabilizing TPL2. In the presence of mutant KRAS, TPL2 phosphorylates and degrades GSK3β, resulting in β-catenin stabilization and activation of the Wnt pathway. These findings elucidate the physiological mechanisms regulating TPL2 and its exploitation by mutant KRAS, underscoring the need to develop TPL2 inhibitors for KRAS-mutant cancers.

Ferroptosis is a type of programmed cell death driven by iron-dependent lipid peroxidation. The TNF-mediated biosynthesis of glutathione has been shown to protect synovial fibroblasts from ferroptosis in the hyperplastic synovium. Ferroptosis induction provides a novel therapeutic approach for rheumatoid arthritis (RA) by reducing the population of synovial fibroblasts. The beginning and maintenance of synovitis in RA are significantly influenced by macrophages, as they generate cytokines that promote inflammation and contribute to the destruction of cartilage and bone. However, the vulnerability of macrophages to ferroptosis in RA remains unclear. In this study, we found that M2 macrophages are more vulnerable to ferroptosis than M1 macrophages in the environment of the arthritis synovium with a high level of iron, leading to an imbalance in the M1/M2 ratio. During ferroptosis, HMGB1 released by M2 macrophages interacts with TLR4 on M1 macrophages, which in turn triggers the activation of STAT3 signaling in M1 macrophages and contributes to the inflammatory response. Knockdown of TLR4 decreased the level of cytokines induced by HMGB1 in M1 macrophages. The ferroptosis inhibitor liproxstatin-1 (Lip-1) started at the presymptomatic stage in collagen-induced arthritis (CIA) model mice, and GPX4 overexpression in M2 macrophages at the onset of collagen antibody-induced arthritis (CAIA) protected M2 macrophages from ferroptotic cell death and significantly prevented the development of joint inflammation and destruction. Thus, our study demonstrated that M2 macrophages are vulnerable to ferroptosis in the microenvironment of the hyperplastic synovium and revealed that the HMGB1/TLR4/STAT3 axis is critical for the ability of ferroptotic M2 macrophages to contribute to the exacerbation of synovial inflammation in RA. Our findings provide novel insight into the progression and treatment of RA.

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells’ susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with – or caused by – ferroptosis.

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation and disease progression. Particularly, mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. However, the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among the most important therapeutic targets. In recent years, strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials. Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria, has shown promise in preclinical trials of various diseases. Mitochondrial components, including mtDNA, mitochondria-located microRNA, and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries. Here, we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases. We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies, as well as the clinical translational situation of related pharmacology agents. Finally, this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon’s optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3–5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders’ cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways.

[ Objective ] Expression of PYL genes in Luffa cylindrica under ABA treatment was studied to provide a reference for gene function and to provide foundation for molecular breeding to improve the quali- ty and yield of L . cylindrica . [ Methods ] Bioinformatics methods were used to analyze the distribution , chromosome location , gene structure , gene collinearity , selection pressure , evolutionary relationships , and cis -acting elements of the PYL gene family in L . cylindrica . Expression of the PYL gene family un- der different concentrations of ABA was verified by qRT-PCR. [ Results ] Eleven LcPYL genes were identi- fied in the genome of L . cylindrica . LcPYL genes had CDSs of 576-966 bp with typical PYR _ PYL _ RCAR _ like structures. Collinear analysis identified seven repeating gene pairs that were predicted to have similar functions. LcPYL promoters contained cis -acting elements associated with plant hormones , and the ex- pression of its members was tissue-specific. Expression of LcPYLs in L . cylindrica fruits did not change at 2 mg / mL ABA. However , the expression of LcPYL5 , LcPYL7 , and LcPYL11 was significantly in- creased at 4 mg / mL ABA , while LcPYL1 and LcPYL7 were expressed at the day of flowering at 8 mg / mL ABA. [ Conclusion ] Our findings suggest that LcPYL1 , LcPYL5 , LcPYL7 , and LcPYL11 may be closely linked to endogenous ABA biosynthesis.

Cell-to-cell mitochondrial transfer has recently been shown to play a role in maintaining physiological functions of cell. We previously illustrated that mitochondrial transfer within osteocyte dendritic network regulates bone tissue homeostasis. However, the mechanism of triggering this process has not been explored. Here, we showed that stressed osteocytes in mice release adenosine diphosphate (ADP), resulting in triggering mitochondrial transfer from healthy osteocytes to restore the oxygen consumption rate (OCR) and to alleviate reactive oxygen species accumulation. Furthermore, we identified that P2Y2 and P2Y6 transduced the ADP signal to regulate osteocyte mitochondrial transfer. We showed that mitochondrial metabolism is impaired in aged osteocytes, and there were more extracellular nucleotides release into the matrix in aged cortical bone due to compromised membrane integrity. Conditioned medium from aged osteocytes triggered mitochondrial transfer between osteocytes to enhance the energy metabolism. Together, using osteocyte as an example, this study showed new insights into how extracellular ADP triggers healthy cells to rescue energy metabolism crisis in stressed cells via mitochondrial transfer in tissue homeostasis.

Renal cell carcinoma (RCC) is recognized as one of the three primary malignant tumors affecting the urinary system, posing a significant risk to human health and life. Despite advancements in understanding RCC, challenges persist in its diagnosis and treatment, particularly in early detection and diagnosis due to issues of low specificity and sensitivity. Consequently, there is an urgent need for the development of effective strategies to enhance diagnostic accuracy and treatment outcomes for RCC. In recent years, with the extensive research on materials for applications in the biomedical field, some materials have been identified as promising for clinical applications, e.g., in the diagnosis and treatment of many tumors, including RCC. Herein, we summarize the latest materials that are being studied and have been applied in the early diagnosis and treatment of RCC. While focusing on their adjuvant effects, we also discuss their technical principles and safety, thus highlighting the value and potential of their application. In addition, we also discuss the limitations of the application of these materials and possible future directions, providing new insights for improving RCC diagnosis and treatment.

This study was designed with the objective of comparing three different plant growth regulators, putrescine (Put), meta-topolin (mT), and 24-epibrassinolide (EBL), in affecting cucumber plants under salt stress. The pilot assessment revealed that all treatments had a significant effect (P < 0.05) on vegetative traits, seedling vigor, total chlorophyll content, and root activity compared to control. The treatment T5 showed the greatest numbers in regard to the above–mentioned traits compared with other combinations. The salt stress study reported that T2 increased superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activities in leaves by 31%, 4.4%, 22.4%, and 35.2%, respectively, in comparison with the control. On the other hand, S3 markedly increased antioxidant enzyme activities, and the activity level was significantly higher than the control and salt treatment. Exogenous S3 had a highly significant effect on glutamine synthetase (GS), glutamate synthase (GOGAT), and (GDH), glutamate dehydrogenase activities in leaves and roots compared with T2. Application of S3 had a highly significant effect on sucrose synthase (SS) and sucrose phosphate synthase (SPS) under salinity stress in leaves and roots compared with other salt stress treatments. The results showed that (5 mM Put + 0.002 ppm mT + 0.001 ppm EBR) treatment alleviated the growth inhibition caused by salt stress by regulating the C-N enzyme activities in cucumber plants. DOI: http://dx.doi.org/10.5281/zenodo.13119418

Burdock (Arctium lappa L.), which belongs to the Compositae family, possesses significant medicinal and nutritional value. Burdock root is abundant in proteins and essential amino acids. In this study, proteins from burdock roots were extracted by alkali extraction and acid sedimentation, and the optimal conditions for protein extraction from burdock roots and protein characteristics were explored. The optimal conditions for protein extraction with a yield rate of 9.03% were 40°C extraction temperature, pH 8.0, a solid–liquid ratio of 1:25 (g/mL), and extraction time of 65 minutes. Single-factor and orthogonal tests on the extraction rate of burdock proteins under different conditions found that the extraction rate of protein from burdock roots were influenced by pH, extraction temperature, solid–liquid ratio, and extraction time, in this order. The solubility and gelation properties of burdock protein were similar to those of soybean protein; however, burdock protein demonstrated 1.2 times the oil absorption capacity and half the water retention capacity of soybean protein. Analysis of the amino acid contents of burdock protein revealed that burdock root contains significant essential and non-essential amino acids, with valine content being the highest.

Abstract Background Mastering the spatial distribution and planting area of paddy can provide a scientific basis for monitoring rice production, and planning grain production layout. Previous remote sensing studies on paddy concentrated in the plain areas with large-sized fields, ignored the fact that rice is also widely planted in vast hilly regions. In addition, the land cover types here are diverse, rice fields are characterized by a scattered and fragmented distribution with small- or medium-sized, which pose difficulties for high-precision rice recognition. Methods In the paper, we proposed a solution based on Sentinel-1 SAR, Sentinel-2 MSI, DEM, and rice calendar data to focus on the rice fields identification in hilly areas. This solution mainly included the construction of rice feature dataset at four crucial phenological periods, the generation of rice standard spectral curve, and the proposal of spectral similarity algorithm for rice identification. Results The solution, integrating topographical and rice phenological characteristics, manifested its effectiveness with overall accuracy exceeding 0.85. Comparing the results with UAV, it presented that rice fields with an area exceeding 400 m2 (equivalent to 4 pixels) exhibited a recognition success rate of over 79%, which reached to 89% for fields exceeding 800 m2. Conclusions The study illustrated that the proposed solution, integrating topographical and rice phenological characteristics, has the capability for charting various rice field sizes with fragmented and dispersed distribution. It also revealed that the synergy of Sentinel-1 SAR and Sentinel-2 MSI data significantly enhanced the recognition ability of rice paddy fields ranging from 400 m2 to 2000 m2.

Abstract Anti-DNA antibodies (Abs), serological hallmarks of systemic lupus erythematosus (SLE) and markers for diagnosis and disease activity, show a specificity for non-nucleic acid molecules, such as N-pyrrolated proteins (pyrP) containing N ε-pyrrole-L-lysine (pyrK) residues. However, the detailed mechanism for the binding of anti-DNA Abs to pyrP remains unknown. In the present study, to gain structural insights into the dual-specificity of anti-DNA Abs, we used phage display to obtain DNA-binding, single-chain variable fragments (scFvs) from SLE-prone mice and found that they also cross-reacted with pyrP. It was revealed that a variable heavy chain (VH) domain is sufficient for the recognition of DNA/pyrP. Identification of an antigenic sequence containing pyrK in pyrP suggested that the presence of both pyrK and multiple acidic amino acid residues plays important roles in the electrostatic interactions with the Abs. X-ray crystallography and computer-predicted simulations of the pyrK-containing peptide-scFv complexes identified key residues of Abs involved in the interaction with the antigens. These data provide a mechanistic insight into the molecular basis of the dual-specificity of the anti-DNA Abs and provide a basis for therapeutic intervention against SLE.

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

The exopolysaccharide (EPS) produced by Pantoea alhagi NX-11, referred to as alhagan, enhances plant stress resistance, improves soil properties, and exhibits notable rheological properties. Despite these benefits, the exact bio-synthetic process of alhagan by P. alhagi NX-11 remains unclear. This study focused on sequencing the complete genome of P. alhagi NX-11 and identifying an alhagan synthesis gene cluster (LQ939_RS12550 to LQ939_RS12700). Gene annotation revealed that alhagan biosynthesis in P. alhagi NX-11 follows the Wzx/Wzy-dependent pathway. Furthermore, transcriptome analysis of P. alhagi NX-11 highlighted significant upregulation of four glycosyltransferase genes (alhH, wcaJ, alhK, and alhM) within the alhagan synthesis gene cluster. These glycosyltransferases are crucial for alhagan synthesis. To delve deeper into this process, two upregulated and uncharacterized glycosyltransferase genes, alhH and alhK, were knocked out. The resulting mutants, ΔalhH and ΔalhK, showed a notable decrease in EPS yield, reduced molecular weight, and altered monosaccharide compositions. These findings contribute to a better understanding of the alhagan biosynthesis mechanism in P. alhagi NX-11.

Power safety named entity recognition (NER) is essential for determining the cause of faults, assessing potential risks, and planning maintenance schedules, contributing to the comprehension and analysis of power safety documentation content and structure. Such analysis is crucial for the development of a knowledge graph within the power safety domain and the augmentation of the associated dataset. This paper introduces a power safety NER model using efficiently learning an encoder that classifies token replacements accurately (ELECTRA) model. This model employs root mean square layer normalization (RMSNorm) and the switched gated linear unit (SwiGLU) activation function, which substitutes the conventional layer normalization (LayerNorm) and the Gaussian error linear units (GeLU). This model also integrates bidirectional long short-term memory (BiLSTM) with conditional random fields (CRF) to bolster performance in NER tasks. Experimental results show that the improved ELECTRA model achieved an F1 value of 93% on the constructed power safety NER dataset. It outperforms the BERT-BiLSTM-CRF model, achieving a 3.3% performance improvement.

Due to the impact of global warming, drought has caused serious damage to China’s ecological environment and social status. This article selects Laibin City in the Guangxi Zhuang Autonomous Region as the research area, utilizing multispectral remote sensing data as the data source and Landsat series image data for relevant preprocessing. It calculates the monthly normalized vegetation index (NDVI) and surface temperature (LST) data for Laibin City. Based on the ecological environment and surface coverage conditions of the research area, the ratio vegetation index (RVI), normalized vegetation moisture index (NDWI), temperature vegetation drought index (TVDI), and conditional vegetation temperature drought index (VTCI) were selected to calculate and invert the drought monitoring results of Laibin City. The drought monitoring results were obtained and overlaid with the vegetation area map to generate the vegetation drought monitoring results of Laibin City. Based on the climate, geography, and ecological characteristics of the monitored area in Laibin City, a specific analysis will be conducted to develop an appropriate TVDI index drought level, and generate vegetation drought level result maps for Laibin City in 2021, 2022, and 2023. Then, a detailed analysis of the vegetation drought situation in Laibin City is conducted according to time and space. Among them, in the past three years, the vegetation areas in Laibin City have experienced drought seasons mostly in summer and autumn. The interannual drought is mainly mild drought, and the proportion of areas with mild drought shows a relatively stable trend. In conclusion, TVDI proves to be a valuable tool for monitoring vegetation drought in Laibin City, offering insights for efficient water resource management strategies.

This paper is concerned with the state estimation problem based on non-fragile set-membership filtering for a class of measurement-saturated memristive neural networks (MNNs) with unknown but bounded (UBB) noises, mixed time delays and missing measurements (MMs), subject to cyber-attacks under the framework of weighted try-once-discard protocol (WTOD protocol). Considering bandwidth-limited open networks, this paper proposes an improved set-membership filtering based on WTOD protocol to partially solve the problem that multiple sensor-related problems and multiple network-induced phenomena influence the state estimation performance of MNNs. Moreover, this paper also discusses the gain perturbations of the estimator and proposes an improved non-fragile estimation framework based on set-membership filtering, which enhances the robustness of the estimation approach. The proposed estimation framework can effectively estimate the state of MNNs with UBB noises, estimator gain perturbations, mixed time-delays, cyber-attacks, measurement saturations and MMs. This paper first utilizes mathematical induction to provide the sufficient conditions for the existence of the desired estimator, and obtains the estimator gain by solving a set of linear matrix inequalities. Then, a recursive optimization algorithm is utilized to achieve optimal estimation performance. The effectiveness of the theoretical results is verified by comparative numerical simulation examples.

The BTB gene superfamily is widely distributed among higher eukaryotes and plays a significant role in numerous biological processes. However, there is limited knowledge about the structure and function of BTB genes in the critically endangered species Alligator sinensis, which is endemic to China. A total of 170 BTB genes were identified from the A. sinensis genome, classified into 13 families, and unevenly distributed across 16 chromosomes. Analysis of gene duplication events yielded eight pairs of tandem duplication genes and six pairs of segmental duplication genes. Phylogenetics shows that the AsBTB genes are evolutionarily conserved. The cis-regulatory elements in the AsBTB family promoter region reveal their involvement in multiple biological processes. Protein interaction network analysis indicates that the protein interactions of the AsBTB genes are centered around CLU-3, mainly participating in the regulation of biological processes through the ubiquitination pathway. The expression profile and protein interaction network analysis of AsBTB genes during sex differentiation and early gonadal development indicate that AsBTB genes are widely expressed in this process and involves numerous genes and pathways for regulation. This study provides a basis for further investigation of the role of the BTB gene in sex differentiation and gonadal development in A. sinensis.

Background: Cancer stem-like cells (CSCs), a distinct subset recognized for their stem cell-like abilities, are intimately linked to the resistance to radiotherapy, metastatic behaviors, and self-renewal capacities in tumors. Despite their relevance, the definitive traits and importance of CSCs in the realm of oncology are still not fully comprehended, particularly in the context of clear cell renal cell carcinoma (ccRCC). A comprehensive understanding of these CSCs’ properties in relation to stemness, and their impact on the efficacy of treatment and resistance to medication, is of paramount importance. Methods: In a meticulous research effort, we have identified new molecular categories designated as CRCS1 and CRCS2 through the application of an unsupervised clustering algorithm. The analysis of these subtypes included a comprehensive examination of the tumor immune environment, patterns of metabolic activity, progression of the disease, and its response to immunotherapy. In addition, we have delved into understanding these subtypes’ distinctive clinical presentations, the landscape of their genomic alterations, and the likelihood of their response to various pharmacological interventions. Proceeding from these insights, prognostic models were developed that could potentially forecast the outcomes for patients with ccRCC, as well as inform strategies for the surveillance of recurrence after treatment and the handling of drug-resistant scenarios. Results: Compared with CRCS1, CRCS2 patients had a lower clinical stage/grading and a better prognosis. The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. The constructed prognostic risk model performed well in both training and validation cohorts, helping to identify patients who may benefit from specific treatments or who are at risk of recurrence and drug resistance. A novel therapeutic target, SAA2, regulating neutrophil and fibroblast infiltration, and, thus promoting ccRCC progression, was identified. Conclusions: Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes.

Plants generate a range of physiological and molecular responses to sustain their growth and development when suffering heat stress. Avocado is a type of tropical fruit tree with high economic value. Most avocado cultivars delete, wither, or even die when exposed to heat stress for a long time, which seriously restricts the introduction and cultivation of avocados. In this study, samples of a heat-intolerant variety (‘Hass’) were treated under heat stress, and the transcriptomics and metabolomics were analyzed, with the expectation of providing information on the variety improvement and domestication of avocados. The differentially expressed genes identified using transcriptome analysis mainly involved metabolic pathways such as plant hormone signal transduction, plant–pathogen interaction, and protein processing in the endoplasmic reticulum. Combined transcriptome and metabolome analysis indicated that the down-regulation of Hass.g03.10206 and Hass.g03.10205 in heat shock-like proteins may result in the reduced Trehalose and Sinapoyl aldehyde content. Metabolomics analysis results indicated that the decrease in Trehalose and Sinapoyl aldehyde content may be an important factor for heat intolerance. These results provide important clues for understanding the physiological mechanisms of adaptation to heat stress in avocados.

Oncidium hybridum Lodd. is an important ornamental flower that is used as both a cut flower and a potted plant around the world; additionally, its pseudobulbs serve as essential carriers for floral organs and flower development. The NAM gene family is crucial for managing responses to various stresses as well as regulating growth in plants. However, the mechanisms by which NAM genes regulate the development of pseudobulbs remain unclear. In this study, a total of 144 NAM genes harboring complete structural domains were identified in O. hybridum. The 144 NAM genes were systematically classified into 14 distinct subfamilies via phylogenetic analysis. Delving deeper into the conserved motifs revealed that motifs 1–6 exhibited remarkable conservation, while motifs 7–10 presented in a few NAM genes only. Notably, NAM genes sharing identical specific motifs were classified into the same subfamily, indicating functional relatedness. Furthermore, the examination of occurrences of gene duplication indicated that the NAM genes display 16 pairs of tandem duplications along with five pairs of segmental duplications, suggesting their role in genetic diversity and potential adaptive evolution. By conducting a correlation analysis integrating transcriptomics and metabolomics at four stages of pseudobulb development, we found that OhNAM023, OhNAM030, OhNAM007, OhNAM019, OhNAM083, OhNAM047, OhNAM089, and OhNAM025 exhibited significant relationships with the endogenous plant hormones jasmonates (JAs), hinting at their potential involvement in hormonal signaling. Additionally, OhNAM089, OhNAM025, OhNAM119, OhNAM055, and OhNAM136 showed strong links with abscisic acid (ABA) and abscisic acid glucose ester (ABA-GE), suggesting the possible regulatory function of these NAM genes in plant growth and stress responses. The 144 NAM genes identified in this study provide a basis for subsequent research and contribute to elucidating the intricate molecular mechanisms of NAM genes in Oncidium and potentially in other species.

Circulating tumor cells (CTCs) are detected in approximately 30% of metastatic non-small-cell lung cancer (NSCLC) cases using the CellSearch system, which relies on EpCAM immunomagnetic enrichment and Cytokeratin detection. This study evaluated the effectiveness of immunomagnetic enrichment targeting oncofetal chondroitin sulfate (ofCS) using recombinant VAR2CSA proteins (rVAR2) to improve the recovery of different NSCLC cell lines spiked into lysed blood samples. Four NSCLC cell lines—NCI-H1563, A549, NCI-H1792, and NCI-H661—were used to assess capture efficiency. The results demonstrated that the combined use of anti-EpCAM antibody and rVAR2 significantly enhanced the capture efficiency to an average of 88.2% compared with 40.6% when using only anti-EpCAM and 56.6% when using only rVAR2. These findings suggest that a dual-marker approach using anti-EpCAM and rVAR2 can provide a more robust and sensitive method for CTC enrichment in NSCLC, potentially leading to better diagnostic and prognostic outcomes.

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.

The ‘diabetic bone paradox’ suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.

Recent neuroimaging studies have shown that the visual cortex plays an important role in representing the affective significance of visual input. The origin of these affect-specific visual representations is debated: they are intrinsic to the visual system versus they arise through reentry from frontal emotion processing structures such as the amygdala. We examined this problem by combining convolutional neural network (CNN) models of the human ventral visual cortex pre-trained on ImageNet with two datasets of affective images. Our results show that in all layers of the CNN models, there were artificial neurons that responded consistently and selectively to neutral, pleasant, or unpleasant images and lesioning these neurons by setting their output to zero or enhancing these neurons by increasing their gain led to decreased or increased emotion recognition performance respectively. These results support the idea that the visual system may have the intrinsic ability to represent the affective significance of visual input and suggest that CNNs offer a fruitful platform for testing neuroscientific theories.

Summary: Neutrophils are important innate immune cells with plasticity, heterogenicity, and functional ambivalency. While bone marrow is often regarded as the primary source of neutrophil production, the roles of extramedullary production in regulating neutrophil plasticity and heterogenicity in autoimmune diseases remain poorly understood. Here, we report that the lack of wingless-type MMTV integration site family member 5 (WNT5) unleashes anti-inflammatory protection against colitis in mice, accompanied by reduced colonic CD8+ T cell activation and enhanced splenic extramedullary myelopoiesis. In addition, colitis upregulates WNT5 expression in splenic stromal cells. The ablation of WNT5 leads to increased splenic production of hematopoietic niche factors, as well as elevated numbers of splenic neutrophils with heightened CD8+ T cell suppressive capability, in part due to elevated CD101 expression and attenuated pro-inflammatory activities. Thus, our study reveals a mechanism by which neutrophil plasticity and heterogenicity are regulated in colitis through WNT5 and highlights the role of splenic neutrophil production in shaping inflammatory outcomes.

Objectives: Osteoarthritis (OA) is characterized by a high prevalence, poor prognosis, and a propensity to lead to disability. Despite the availability of standard therapies, they are associated with potential side effects and don't provide a complete cure for patients. Consequently, there is an urgent demand for the development of novel drugs. Method: The gene expression profiles (GSE64394, GSE178557 and GSE215039) of normal and OA chondrocytes samples were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by the ''LIMMA'' R package. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted using the R package clusterProfiler. A protein-protein (PPI) interaction network was performed to identify hub genes by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Small molecule compounds linked to OA were predicted through the NetworkAnalyst platform. Finally, molecular docking was conducted using AutoDock and Pymol software. Results: We identified 98 DEGs primarily implicated in endochondral ossification, extracellular matrix degradation, and Wnt signaling pathways. 23 DEGs were closely associated with OA, and 10 hub genes were found to be potential drug targets for OA. Two new targeted compounds, tetrachlorodibenzodioxin (TCDD) and valproic acid (VPA), were screened. And they both exhibited strong binding affinity to their respective targets. Conclusions: Reducing exposure to TCDD could be a crucial strategy in preventing OA, and VPA has gained recognition as a novel drug candidate for OA treatment.

Abstract Cancer immunotherapy, alone or in combination with conventional therapies, has revolutionized the landscape of antineoplastic treatments, with dendritic cells (DC) emerging as key orchestrators of anti-tumor immune responses. Among the distinct DC subsets, conventional type 1 dendritic cells (cDC1) have gained prominence due to their unique ability to cross-present antigens and activate cytotoxic T lymphocytes. This review summarizes the distinctive characteristics of cDC1, their pivotal role in anticancer immunity, and the potential applications of cDC1-based strategies in immunotherapy.

Pancreatic cancer is a malignant tumor of the digestive system that is highly malignant, difficult to treat, and confers a poor prognosis for patients. BRAF-activated noncoding RNA (BANCR) has been proven to play an important role in the invasion and metastasis of pancreatic cancer. In this study, we focused on BANCR as a potential therapeutic target for human pancreatic cancer. The BANCR level in pancreatic cancer tissues and cells is affected by m6A methylation. Based on this, the aim of our study was to investigate the effect of a highly potent and selective first-in-class catalytic inhibitor of METTL3 (STM2457) on BANCR m6A methylation and its malignant biological behaviors in pancreatic cancer. The relationship between BANCR expression and BANCR m6A modification was detected with RT-qPCR and MeRIP-PCR. The expression of methyltransferase-like 3 (METTL3), the key enzyme involved in m6A methylation, in pancreatic cancer tissues was detected using a Western blot. STM2457 was used in vitro to investigate its resistance to the proliferation, invasion, and metastasis of pancreatic cancer cells. BANCR was overexpressed in pancreatic cancer tissues and cells, which was associated with poor clinical outcomes and validated in pancreatic cancer cell lines. m6A modification was highly enriched within BANCR and enhanced its expression. Remarkably, STM2457 inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells by down-regulating BANCR m6A modifications. This study demonstrates the promise of BANCR as a new diagnostic and therapeutic target for pancreatic cancer and reveals the therapeutic effect that STM2457 exerts on pancreatic cancer by down-regulating BANCR m6A modifications.

Abstract Background The metrics for assessing the yield of crops in the field include the number of ears per unit area, the grain number per ear, and the thousand-grain weight. Typically, the ear number per unit area contributes the most to the yield. However, calculation of the ear number tends to rely on traditional manual counting, which is inefficient, labour intensive, inaccurate, and lacking in objectivity. In this study, two novel extraction algorithms for the estimation of the wheat ear number were developed based on the use of terrestrial laser scanning (TLS) in conjunction with the density-based spatial clustering (DBSC) algorithm based on the normal and the voxel-based regional growth (VBRG) algorithm. The DBSC involves two steps: (1) segmentation of the point clouds using differences in the normal vectors and (2) clustering of the segmented point clouds using a density clustering algorithm to calculate the ear number. The VBRG involves three steps: (1) voxelization of the point clouds, (2) construction of the topological relationships between the voxels as a connected region using the k-dimensional tree, and (3) detection of the wheat ears in the connected areas using a regional growth algorithm. Results The results demonstrated that DBSC and VBRG were promising in estimating the number of ears for different cultivars, planting densities, N fertilization rates, and growth stages of wheat (RMSE = 76 ~ 114 ears/m2, rRMSE = 18.62 ~ 27.96%, r = 0.76 ~ 0.84). Comparing the performance of the two algorithms, the overall accuracy of the DBSC (RMSE = 76 ears/m2, rRMSE = 18.62%, r = 0.84) was better than that of the VBRG (RMSE = 114 ears/m2, rRMSE = 27.96%, r = 0.76). It was found that with the DBSC, the calculation in points as units permitted more detailed information to be retained, and this method was more suitable for estimation of the wheat ear number in the field. Conclusions The algorithms adopted in this study provide new approaches for non-destructive measurement and efficient acquisition of the ear number in the assessment of the wheat yield phenotype.

Abstract Objective Catheter-associated urinary tract infections (CAUTI) are common worldwide, but due to limited resources, its actual burden in low-income countries is unknown. Currently, there are gaps in knowledge about CAUTI due to lack of surveillance activities in Sierra Leone. In this prospective cohort study, we aimed to determine the incidence of CAUTI and associated antibiotic resistance in two tertiary hospitals in different regions of Sierra Leone. Results The mean age of the 459 recruited patients was 48.8 years. The majority were females (236, 51.3%). Amongst the 196 (42.6%) catheterized patients, 29 (14.8%) developed CAUTI. Bacterial growth was reported in 32 (84%) patients. Escherichia coli (14, 23.7%), Klebsiella pneumoniae (10, 17.0%), and Klebsiella oxytoca (8, 13.6%) were the most common isolates. Most isolates were ESBL-producing Enterobacteriaceae (33, 56%) and WHO Priority 1 (Critical) pathogens (38, 71%). Resistance of K. pneumoniae, K. oxytoca, E. coli, and Proteus mirabilis was higher with the third-generation cephalosporins and penicillins but lower with carbapenems, piperacillin-tazobactam and amikacin. To reduce the high incidence of CAUTI and multi-drug resistance organisms, urgent action is needed to strengthen the microbiology diagnostic services and develop and implement catheter bundles that provide clear guidance for catheter insertion, care and removal.

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

Due to protection of extracellular polymeric substances, the therapeutic efficiency of conventional antimicrobial agents is often impeded by their poor infiltration and accumulation in biofilm. Herein, one type of surface charge adaptable nitric oxide (NO) nanogenerator was developed for biofilm permeation, retention and eradication. This nanogenerator (PDG@Au–NO/PBAM) is composed of a core-shell structure: thermo-sensitive NO donor conjugated AuNPs on cationic poly(dopamine-co-glucosamine) nanoparticle (PDG@Au–NO) served as core, and anionic phenylboronic acid-acryloylmorpholine (PBAM) copolymer was employed as a shell. The NO nanogenerator featured long circulation and good biocompatibility. Once the nanogenerator reached acidic biofilm, its surface charge would be switched to positive after shell dissociation and cationic core exposure, which was conducive for the nanogenerator to infiltrate and accumulate in the depth of biofilm. In addition, the nanogenerator could sustainably generate NO to disturb the integrity of biofilm at physiological temperature, then generate hyperthermia and explosive NO release upon NIR irradiation to efficiently eradicate drug-resistant bacteria biofilm. Such rational design offers a promising approach for developing nanosystems against biofilm-associated infections.