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Abstract. Cancer is a major global health issue. Effective therapeutic strategies can prolong patients' survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.

Abstract Background The impact of lower urinary tract symptoms (LUTS) on the quality of life of patients with benign prostatic hyperplasia (BPH) has been rarely reported. Additionally, the challenges faced by these patients in seeking medical care have often been overlooked. In order to explore the personal struggles caused by LUTS and the difficulties or barriers experienced by Chinese patients with BPH when seeking help, we conducted a qualitative interview study. Methods Qualitative interviews were conducted among 46 patients with BPH who were hospitalized in three tertiary hospitals in China from July 2021 to November 2022. Grounded theory was adopted as the methodology for the qualitative study. After obtaining written informed consent from the study participants, semi-structured interviews were conducted according to the question guidelines. The interview process was audio-recorded; subsequently, the recordings were transcribed, coded, and thematically analyzed. Results The difficulties faced by Chinese patients with BPH were classified into seven main themes: (i) disturbed life, (ii) mental burden, (iii) disease cognition and communication, (iv) delayed treatment, (v) medication status, (vi) hospital visits barriers, and (vii) medical insurance issues. Further, each theme was subdivided into 2–5 sub-themes. Conclusions LUTS have a certain effect on the life and spirit of patients with BPH. These patients face different degrees of difficulties in treatment and hospital visits. Therefore, better healthcare systems and additional social support are crucial for improving the current plight of these patients.

Abstract The prevalence of myopia (nearsightedness) is increasing to alarming levels, but its etiology remains poorly understood. Because both laboratory and clinical findings suggest an etiologic role for circadian rhythms in myopia development, we assayed gene expression by RNA-Seq in retina and choroid at the onset of unilateral experimental myopia in chick, isolating tissues every 4 h during a single 24-h period from myopic and contralateral control eyes. Occluded versus open eye gene expression differences varied considerably over the 24-h sampling period, with some occurring at multiple times of day but with others showing differences at only a single investigated timepoint. Some of the genes identified in retina or choroid of chick myopia were previously identified as candidate genes for common human myopia. Like differentially expressed genes, pathways identified by Gene Set Enrichment Analysis also varied dramatically by sampling time. Considered with other laboratory data, human genetic and epidemiology data, these findings further implicate circadian events in myopia pathogenesis. The present results emphasize a need to include time of day in mechanistic studies of myopia and to assess circadian biology directly in trying to understand better the origin of myopia and to develop more effective therapies.

Abstract Background Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa. Methods CircSTX6 (hsa_circ_0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity. Results We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors. Conclusion These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa.

Abstract Transport of rodlike particles in confinement environments of macromolecular networks plays crucial roles in many important biological processes and technological applications. The relevant understanding has been limited to thin rods with diameter much smaller than network mesh size, although the opposite case, of which the dynamical behaviors and underlying physical mechanisms remain unclear, is ubiquitous. Here, we solve this issue by combining experiments, simulations and theory. We find a nonmonotonic dependence of translational diffusion on rod length, characterized by length commensuration-governed unconventionally fast dynamics which is in striking contrast to the monotonic dependence for thin rods. Our results clarify that such a fast diffusion of thick rods with length of integral multiple of mesh size follows sliding dynamics and demonstrate it to be anomalous yet Brownian. Moreover, good agreement between theoretical analysis and simulations corroborates that the sliding dynamics is an intermediate regime between hopping and Brownian dynamics, and provides a mechanistic interpretation based on the rod-length dependent entropic free energy barrier. The findings yield a principle, that is, length commensuration, for optimal design of rodlike particles with highly efficient transport in confined environments of macromolecular networks, and might enrich the physics of the diffusion dynamics in heterogeneous media.

Abstract Background Many viruses enter host cells by hijacking endosomal trafficking. CapZ, a canonical actin capping protein, participates in endosomal trafficking, yet its precise role in endocytosis and virus infection remains elusive. Results Here, we showed that CapZ was transiently associated with early endosomes (EEs) and was subsequently released from the matured EEs after the fusion of two EEs, which was facilitated by PI(3)P to PI(3,5)P2 conversion. Vacuolin-1 (a triazine compound) stabilized CapZ at EEs and thus blocked the transition of EEs to late endosomes (LEs). Likewise, artificially tethering CapZ to EEs via a rapamycin-induced protein–protein interaction system blocked the early-to-late endosome transition. Remarkably, CapZ knockout or artificially tethering CapZ to EEs via rapamycin significantly inhibited flaviviruses, e.g., Zika virus (ZIKV) and dengue virus (DENV), or beta-coronavirus, e.g., murine hepatitis virus (MHV), infection by preventing the escape of RNA genome from endocytic vesicles. Conclusions These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).

The world-wide prevalence of myopia (nearsightedness) is increasing, but its pathogenesis is incompletely understood. Among many putative mechanisms, laboratory and clinical findings have implicated circadian biology in the etiology of myopia. Consistent with a circadian hypothesis, we recently reported a marked variability in diurnal patterns of gene expression in two crucial tissues controlling post-natal refractive development - the retina and choroid-at the onset of form-deprivation myopia in chick, a widely studied and validated model. To extend these observations, we assayed gene expression by RNA-Seq in retina and choroid during the progression of established unilateral form-deprivation myopia of chick. We assayed gene expression every 4 hours during a single day from myopic and contralateral control eyes. Retinal and choroidal gene expression in myopic vs. control eyes during myopia progression differed strikingly at discrete times during the day. Very few differentially expressed genes occurred at more than one time in either tissue during progressing myopia. Similarly, Gene Set Enrichment Analysis pathways varied markedly by time during the day. Some of the differentially expressed genes in progressing myopia coincided with candidate genes for human myopia, but only partially corresponded with genes previously identified at myopia onset. Considering other laboratory findings and human genetics and epidemiology, these results further link circadian biology to the pathogenesis of myopia; but they also point to important mechanistic differences between the onset of myopia and the progression of established myopia. Future laboratory and clinical investigations should systematically incorporate circadian mechanisms in studying the etiology of myopia and in seeking more effective treatments to normalize eye growth in children.

Abstract Background Maize (Zea mays L.) is at the vanguard facing the upcoming breeding challenges. However, both a super pan-genome for the Zea genus and a comprehensive genetic variation map for maize breeding are still lacking. Results Here, we construct an approximately 6.71-Gb pan-Zea genome that contains around 4.57-Gb non-B73 reference sequences from fragmented de novo assemblies of 721 pan-Zea individuals. We annotate a total of 58,944 pan-Zea genes and find around 44.34% of them are dispensable in the pan-Zea population. Moreover, 255,821 common structural variations are identified and genotyped in a maize association mapping panel. Further analyses reveal gene presence/absence variants and their potential roles during domestication of maize. Combining genetic analyses with multi-omics data, we demonstrate how structural variants are associated with complex agronomic traits. Conclusions Our results highlight the underexplored role of the pan-Zea genome and structural variations to further understand domestication of maize and explore their potential utilization in crop improvement.

In recent years, the properties of the ore mined in the Anqian area have changed greatly. In order to provide a basis for the formulation of the ore beneficiation process, it is necessary to carry out detailed process mineralogical research. In this paper, with the help of optical microscope, chemical analysis, X-ray diffraction and other analysis and detection methods, a comprehensive and systematic study on the chemical composition, mineral composition, dissemination particle size and inlay characteristics of the ore samples in the Anqian area was carried out. Research results show that the iron grade in the ore is 29.25%, and the main iron-bearing minerals are magnetite, hematite, limonite, and pyrite. The magnetite content is 31.65% and the hematite content is 6.53%. Iron ore type iron ore; gangue is mainly quartz, with a content of 45.44%, followed by hornblende. The automorphic crystal structure is more common in hematite in the ore, and the semi-automorphic crystal structure is more common in the magnetite. Individual magnetite is an alternate structure between two or more minerals. The particle size of magnetite and hematite is uneven, and the multi-stage grinding and multi-stage magnetic separation process can be selected.

Abstract It is more and more important to analyse and process complex data for gaining more valuable knowledge and making more accurate decisions. The multigranulation decision theory based on conditional probability and cost loss has the advantage of processing decision‐making problems from multi‐levels and multi‐angles, and the neighbourhood rough set model (NRS) can facilitate the analysis and processing of numerical or mixed type data, and can address the limitation of multigranulation decision‐theoretic rough sets (MG‐DTRS), which is not easy to cope with complex data. Based on the in‐depth study of hybrid‐valued decision systems and MG‐DTRS models, this study analysed neighbourhood MG‐DTRS (NMG‐DTRS) deeply by fusing MG‐DTRS and NRS; a matrix‐based approach for approximation sets of NMG‐DTRS model was proposed on the basis of the matrix representations of concepts; the positive, boundary and negative domains were constructed from the matrix perspective, and the concept of positive decision recognition rate was introduced. Furthermore, the authors explored the related properties of NMG‐DTRS model, and designed and described the corresponding solving algorithms in detail. Finally, some experimental results that were employed not only verified the effectiveness and feasibility of the proposed algorithm, but also showed the relationship between the decision recognition rate and the granularity and threshold.

Accumulating evidence has revealed that the dysregulation of circular RNAs (circRNAs) plays crucial roles in the occurrence and progression of cancers. However, the aberrant expression profile and dysfunction of circRNAs in non-small cell lung cancer (NSCLC) have not been fully explored. Herein, we discovered that a circRNA, hsa_circ_0001666 (circ0001666), was highly expressed in NSCLC tissues and cell lines, and it was positively correlated with NSCLC tumor pathological grade and lymph node metastasis. Moreover, Kaplan-Meier survival analysis implied that NSCLC patients with high circ0001666 expression were negatively correlated with favorable survival. Functionally, circ0001666 could promote migration and invasion of NSCLC cells in vitro and in vivo. Mechanistically, circ0001666 could act as a sponge to miR-1184/miR-548I and upregulate the expression of AGO1, thereby promoting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway in NSCLC cells. Collectively, these findings demonstrated that circ0001666 could serve as an oncogene to promote the migration and invasion of NSCLC via a novel miR-1184/miR-548I/AGO1 axis, which might be a promising therapeutic target for NSCLC treatment.

Abstract Tumor-associated macrophages have emerged as crucial factors for metastases. Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis (BM). However, the underlying mechanism of how activated microglia promote brain metastasis of non-small cell lung cancer (NSCLC) remains elusive. Here, we purified cell lines with brain-metastatic tropism and employed a co-culture system to reveal their communication with microglia. By single-cell RNA-sequencing and transcriptome difference analysis, we identified IL6 as the key regulator in brain-metastatic cells (A549-F3) to induce anti-inflammatory microglia via JAK2/STAT3 signaling, which in turn promoted the colonization process in metastatic A549-F3 cells. In our clinical samples, patients with higher levels of IL6 in serum showed higher propensity for brain metastasis. Additionally, the TCGA (The Cancer Genome Atlas) data revealed that NSCLC patients with a lower level of IL6 had a longer overall survival time compared to those with a higher level of IL6. Overall, our data indicate that the targeting of IL6/JAK2/STAT3 signaling in activated microglia may be a promising new approach for inhibiting brain metastasis in NSCLC patients.

Abstract The aberrant regulation of PD‐L1 in tumor cells remains poorly understood. Here, the authors systematically investigate the endosomal trafficking of plasma membrane PD‐L1 in tumor cells. They show that plasma membrane PD‐L1 is continuously internalized, and then trafficked from early endosomes to multivesicular bodies/late endosomes, recycling endosomes, lysosomes, and/or extracellular vesicles (EVs). This constitutive endocytic trafficking of PD‐L1 is Rab5‐ and clathrin‐dependent. Triazine compound 6J1 blocks the endosomal trafficking of PD‐L1 and induces its accumulation in endocytic vesicles by activating Rab5. 6J1 also promotes exosomal PD‐L1 secretion by activating Rab27. Together, these effects result in a decrease in the membrane level of PD‐L1 in 6J1‐treated tumor cells and enables tumor cells to be more susceptible to the tumor‐killing activity of T cells in vitro. 6J1 also increases tumor‐infiltrating cytotoxic T cells and promotes chemokines secretion in the tumor microenvironment. Rab27 knockdown abolishes 6J1‐induced PD‐L1 secretion in EVs and revokes the exhausted tumor‐infiltrating T cells in tumors, thereby improving the anticancer efficacy of 6J1. Furthermore, a combination of 6J1 and an anti‐PD‐1 antibody significantly improves the anticancer immune response. Therefore, manipulating PD‐L1 endosomal trafficking provides a promising means to promote an anticancer immune response in addition to the immune checkpoint‐blocking antibody therapy.

The Al–Sb–Sn ternary system was studied by combining experimental measurement and thermodynamic modeling. The three vertical cross-sections of Al–SnSb, Sn–AlSb, and Sb–AlSn were measured by Differential Scanning Calorimetry (DSC). Based on the Calculation of Phase Diagram (CALPHAD) method, the thermodynamic modeling of the Al–Sb–Sn ternary system was carried out based on the evaluated experimental data by FactSage. A set of thermodynamic model parameters consistent with the experimental data was obtained.

Abstract Background Cisplatin (CDDP) has become a standard-of-care treatment for muscle-invasive bladder cancer (MIBC), while chemoresistance remains a major challenge. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the regulatory functions as well as complexities of circRNAs in modulating CDDP-based chemotherapy in bladder cancer are yet to be well revealed. Methods Through analyzing the expression profile of circRNAs in bladder cancer tissues, RNA FISH, circRNA pull-down assay, mass spectrometry analysis and RIP, circLIFR was identified and its interaction with MSH2 was confirmed. The effects of circLIFR and MSH2 on CDDP-based chemotherapy were explored by flow cytometry and rescue experiments. Co-IP and Western blot were used to investigate the molecular mechanisms underlying the functions of circLIFR and MSH2. Biological implications of circLIFR and MSH2 in bladder cancer were implemented in tumor xenograft models and PDX models. Results CircLIFR was downregulated in bladder cancer and expression was positively correlated with favorable prognosis. Moreover, circLIFR synergizing with MSH2, which was a mediator of CDDP sensitivity in bladder cancer cells, positively modulated sensitivity to CDDP in vitro and in vivo. Mechanistically, circLIFR augmented the interaction between MutSα and ATM, ultimately contributing to stabilize p73, which triggered to apoptosis. Importantly, MIBC with high expression of circLIFR and MSH2 was more sensitive to CDDP-based chemotherapy in tumor xenograft models and PDX models. Conclusions CircLIFR could interact with MSH2 to positively modulate CDDP-sensitivity through MutSα/ATM-p73 axis in bladder cancer. CircLIFR and MSH2 might be act as promising therapeutic targets for CDDP-resistant bladder cancer.

Background This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. Methods In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. Results In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14–1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p

Introduction Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. Methods Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. Results Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84–0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. Conclusions We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.

The dissimilar self-piercing riveted (SPR) joints between aluminium-lithium alloy (AL1420) and titanium (TA1) sheets were investigated. The effects of the overlap form and rivet hardness on the forming structures, quasi-static and fatigue characteristics of the considered dissimilar joints were analysed systematically. A new curve-fitting method was adopted to fit the fatigue data of SPR joints. The results show that the potential weak areas in the forming structures could be changed using different overlap forms or rivet hardness. The overlap form for the dissimilar joints plays a more important role on the joint strength compared to the rivet hardness, but has little influence on the energy absorption. The fatigue property of the dissimilar joints is improved with the rivet hardness increased and the joints taken TA1 as the locked sheet possess a better fatigue life. The rivet hardness presents an obvious influence on the fatigue fracture path. The forming structures of the dissimilar joints are significantly affected by the overlap forms, which finally results in the fatigue fracture originated in different initiation sites.

Acute rejection (AR) is closely associated with renal allograft dysfunction. Here, we utilised RNA sequencing (RNA-Seq) and bioinformatic methods to characterise the peripheral blood mononuclear cells (PBMCs) of patients with acute renal allograft rejection. Pretransplant blood samples were collected from 32 kidney allograft donors and 42 corresponding recipients with biopsies classified as T cell-mediated rejection (TCMR, n = 18), antibody-mediated rejection (ABMR, n = 5), and normal/non-specific changes (non-AR, n = 19). The patients with TCMR and ABMR were assigned to the AR group, and the patients with normal/non-specific changes (n = 19) were assigned to the non-AR group. We analysed RNA-Seq data for identifying differentially expressed genes (DEGs), and then gene ontology (GO) analysis, Reactome, and ingenuity pathway analysis (IPA), protein—protein interaction (PPI) network, and cell-type enrichment analysis were utilised for bioinformatics analysis. We identified DEGs in the PBMCs of the non-AR group when compared with the AR, ABMR, and TCMR groups. Pathway and GO analysis showed significant inflammatory responses, complement activation, interleukin-10 (IL-10) signalling pathways, classical antibody-mediated complement activation pathways, etc., which were significantly enriched in the DEGs. PPI analysis showed that IL-10, VEGFA, CXCL8, MMP9, and several histone-related genes were the hub genes with the highest degree scores. Moreover, IPA analysis showed that several proinflammatory pathways were upregulated, whereas antiinflammatory pathways were downregulated. The combination of NFSF14+TANK+ANKRD 33 B +HSPA1B was able to discriminate between AR and non-AR with an AUC of 92.3% (95% CI 82.8–100). Characterisation of PBMCs by RNA-Seq and bioinformatics analysis demonstrated gene signatures and biological pathways associated with AR. Our study may provide the foundation for the discovery of biomarkers and an in-depth understanding of acute renal allograft rejection.

Actin filaments (F-actin) have been implicated in various steps of endosomal trafficking, and the length of F-actin is controlled by actin capping proteins, such as CapZ, which is a stable heterodimeric protein complex consisting of α and β subunits. However, the role of these capping proteins in endosomal trafficking remains elusive. Here, we found that CapZ docks to endocytic vesicles via its C-terminal actin-binding motif. CapZ knockout significantly increases the F-actin density around immature early endosomes, and this impedes fusion between these vesicles, manifested by the accumulation of small endocytic vesicles in CapZ-knockout cells. CapZ also recruits several RAB5 effectors, such as Rabaptin-5 and Rabex-5, to RAB5-positive early endosomes via its N-terminal domain, and this further activates RAB5. Collectively, our results indicate that CapZ regulates endosomal trafficking by controlling actin density around early endosomes and recruiting RAB5 effectors.

Metastatic spinal tumors (MST) have high rates of morbidity and mortality. MST can destroy the vertebral body or compress the nerve roots, resulting in an increased risk of pathological fractures and intractable pain. Here, we elaborately reviewed the currently available therapeutic options for MST according to the following four aspects: surgical management, minimally invasive therapy (MIT), radiation therapy, and systemic therapy. In particular, these aspects were classified and introduced to show their developmental process, clinical effects, advantages, and current limitations. Furthermore, with the improvement of treatment concepts and techniques, we discovered the prevalent trend toward the use of radiation therapy and MIT in clinic therapies. Finally, the future directions of these treatment options were discussed. We hoped that along with future advances and study will lead to the improvement of living standard and present status of treatment in patients with MST.

It is an important subject to mine valuable knowledge from complex and massive data in the era of big data. Rough set theory is a new mathematical tool for dealing with uncertain and inaccurate data, decision-theoretic rough set model (DTRS), as an extension of classical rough set model, is used to analyze decision information systems and multi-granulation decision-theoretic rough set model (MG-DTRS) can analyze and process target concepts from different angles and levels. However, the classical DTRS model exists some limitations in dealing numerical or hybrid-valued data. Considering the different influence of numerical features and symbolic features on decision-making, the paper proposes an incomplete neighborhood multi-granulation decision-theoretic rough set model in hybrid-valued decision system through integrating MG-DTRS with neighbourhood rough sets, and two types of neighborhood multi-granulation decision-theoretic set models are emphatically analysed. Furthermore, taking pessimistic and optimistic neighborhood multi-granulation decision-theoretic rough sets as examples, the implementation algorithms and related properties of the two type of models are studied. Finally, the relationship between the proposed model and other models is analyzed through formula derivation. The model proposed in this paper can effectively solve the decision-making problem of hybrid-valued incomplete information system through multi-angle and multi-level analysis.

Chromosomal rearrangements (CRs) play important roles in karyotype diversity and speciation. While many CR breakpoints have been characterized at the sequence level in yeast, insects, and primates, little is known about the structure of evolutionary CR breakpoints in plant genomes, which are much more dynamic in genome size and sequence organization. Here, we report identification of breakpoints of a translocation between chromosome arms 4L and 5L of Triticeae, which is fixed in several species, including diploid wheat and rye, by comparative mapping and analysis of the draft genome and chromosome survey sequences of the Triticeae species. The wheat translocation joined the ends of breakpoints downstream of a WD40 gene on 4AL and a gene of the PMEI family on 5AL. A basic helix-loop-helix transcription factor gene in 5AL junction was significantly restructured. Rye and wheat share the same position for the 4L breakpoint, but the 5L breakpoint positions are not identical, although very close in these two species, indicating the recurrence of 4L/5L translocations in the Triticeae. Although barley does not carry the translocation, collinearity across the breakpoints was violated by putative inversions and/or transpositions. Alignment with model grass genomes indicated that the translocation breakpoints coincided with ancient inversion junctions in the Triticeae ancestor. Our results show that the 4L/5L translocation breakpoints represent two CR hotspots reused during Triticeae evolution, and support breakpoint reuse as a widespread mechanism in all eukaryotes. The mechanisms of the recurrent translocation and its role in Triticeae evolution are also discussed.

Aims: We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. Methods: Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. Results: 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p

To improve the diamond bit property, this paper studies the influencing mechanism of silicon carbide (SiC) and its additive amount on diamond bit; in the study, firstly, the SiC particles in different weight percentage were added in the matrix, then the drilling bit was fabricated, and finally the indoors drilling test was made. The results show that proper concentration of SiC particles can improve the synchronic wear property of diamond bit and matrix; at the additive amount 5.5% (wt%), the drilling efficiency increases by 55% as compared with the conventional bit; besides, compared with the diamond particles, the SiC-impregnated force by matrix is limited, so it can be more easily peeled off to form a pit on the matrix surface, which helps to increase the specific pressure of bit’s crown (bit) and further promote the micro-wears morphology of matrix; at last, the free-state SiC residue on hole bottom can on one hand has a sharpening effect on the single-particle diamond in matrix to increase the diamond protrusion height and improve the machinability of single-particle diamond, on the other hand, it can enhance the solid component, promoting the erosive effect of flushing fluid on matrix.

W3 is essential for β-diketone biosynthesis but suppresses its hydroxylation. Loss-of-function mutation w3 significantly increased cuticle permeability in terms of water loss and chlorophyll efflux.

Huntington disease (HD) represents a family of neurodegenerative diseases that are caused by misfolded proteins. The misfolded proteins accumulate in the affected brain regions in an age-dependent manner to cause late-onset neurodegeneration. Transgenic mouse models expressing the HD protein, huntingtin, have been widely used to identify therapeutics that may retard disease progression. Here we report that Berberine (BBR), an organic small molecule isolated from plants, has protective effects on transgenic HD (N171-82Q) mice. We found that BBR can reduce the accumulation of mutant huntingtin in cultured cells. More importantly, when given orally, BBR could effectively alleviate motor dysfunction and prolong the survival of transgenic N171-82Q HD mice. We found that BBR could promote the degradation of mutant huntingtin by enhancing autophagic function. Since BBR is an orally-taken drug that has been safely used to treat a number of diseases, our findings suggest that BBR can be tested on different HD animal models and HD patients to further evaluate its therapeutic effects.

Background Declining birth rates during the pandemic have led to concerns about the potential impact of the of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on fertility among men. As previous studies have had inconsistent conclusions, we conducted a meta-analysis to evaluate the effects of SARS-CoV-2 on semen parameters. Methods We searched several databases for articles published between 1 January 2020 and 25 July 2023. We performed a robust screening process based on predetermined inclusion and exclusion criteria and, following quality assessment, extracted data from high-quality studies for the meta-analysis. We determined the P-values and 95% confidence intervals (CIs) for both continuous and dichotomous variables, which we described using mean differences (MDs) and odds ratios (ORs), respectively. Lastly, we used the leave-one-out approach for our sensitivity analysis, and Begg’s and Egger’s tests to determine publication bias. Results We included 39 articles with 1887 cases and 2097 controls. In patients infected with SARS-CoV-2, the sperm volume (MD=−0.29; 95% CI=−0.50, −0.07; P = 0.008) and concentration (MD= −8.71; 95% CI = −16.94, −0.48; P=0.04) were decreased, which increased oligospermia risk (OR=2.49; 95% CI = 1.04, 5.99; P = 0.04). Furthermore, we observed reduced sperm motility (MD=−8.18; 95% CI=−12.19, −4.17; P<0.001) and increased immotility (MD=4.06; 95% CI=1.57, 6.54; P=0.001) in infected patients, which increased asthenospermia risk (OR=3.86; 95%CI=1.83, 8.14; P=0.0004). We also saw a decreased proportion of semen with normal sperm morphology (MD=−1.67; 95% CI=−2.68, −0.66; P=0.001) and an increased proportion of semen with abnormal sperm morphology (MD=−1.31; 95% CI=−2.14, −0.49; P=0.002,), along with increases in teratospermia (OR=1.98; 95% CI=1.00, 3.92; P=0.05) in infected compared non-infected patients. Although we found consistency within most subgroups, we observed differences in severity, follow-up time, and country of origin. The results of the main meta-analysis results remained stable in the sensitivity analysis, while Begg’s and Egger’s tests showed no publication bias. Conclusions Based on sufficient evidence, we see that the effects of SARSCoV-2 on semen parameters resulted in a decline in male fertility. The increased severity and shorter duration of the SARS-CoV-2 infection increased the likelihood of altering of semen parameters. [ABSTRACT FROM AUTHOR]

The utilization of low-dimensional perovskites (LDPs) as interlayers on three-dimensional (3D) perovskites has been regarded as an efficient strategy to enhance the performance of perovskite solar cells. Yet, the formation mechanism of LDPs and their impacts on the device performance remain elusive. Herein, we use dimensional engineering to facilitate the controllable growth of 1D and 2D structures on 3D perovskites. The differences of isomeric ligands in electrostatic potential distribution and steric effects for intermolecular forces contribute to different LDPs. The 1D structure facilitates charge transfer with favored channel orientation and energy level alignment. This approach enables perovskite solar modules (PSMs) using 2,2',7,7'-tetrakis[ N,N-di(4-methoxyphenyl) amino]-9,9'-spirobifluorene to achieve an efficiency of 20.20% over 10 by 10 square centimeters (cm2) and 22.05% over 6 by 6 cm2. In particular, a PSM (6 by 6 cm2) using poly[bis(4-phenyl)(2,4,6-trimethylphenyl) amine] maintains an initial efficiency of ~95% after 1000 hours under the rigorous ISOS-L-3 accelerated aging tests, marking a record for the highest stability of n-i-p structure modules. [ABSTRACT FROM AUTHOR]

Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29- mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression. [ABSTRACT FROM AUTHOR]

The article informs about how Intracellular cargo transport is fundamental for a broad range of cellular activities, especially for the processes involving extensive and rapid rearrangements of cellular components, such as cell division and neuromodulation. It also mentions how actin-based motors, unconventional class V myosins are critical in transporting a diverse array of intracellular cargoes, including different types of organelles, vesicles, and protein complexes.

In mouse testes, Musashi-1 (Msi-1) was predominantly expressed in the cytoplasm and nuclei of Sertoli cells. Here we demonstrate that knockdown of Msi-1 in Sertoli cells altered the levels and distribution of blood-testis barrier (BTB)-associated proteins. Moreover, Msi-1 knockdown in vivo disrupted BTB functional structure and spermatogenesis. In addition, we report a novel role of Msi-1 in regulating Sertoli cells survival following heat-induced injury. Endogenous Msi-1 protein in heat-treated Sertoli cells was recruited to stress granules. The formation of stress granules was considerably disrupted, and apoptosis was significantly up-regulated in Msi-1-knockdown Sertoli cells after heat treatment. p-ERK1/2 acted downstream of stress granule formation, and inhibition of p-ERK1/2 signaling triggered Sertoli cell apoptosis upon heat stress. In conclusion, we demonstrate that Msi-1 is critical for constructing a functional BTB structure and maintaining spermatogenesis. We also note a role for Msi-1 in regulating Sertoli cell fate following heat-induced injury, likely through the induction of stress granule formation and subsequent activation of p-ERK1/2 signaling., (© 2015 ErLin et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Mobilization of intracellular Ca(2+) stores is involved in many diverse cell functions, including: cell proliferation; differentiation; fertilization; muscle contraction; secretion of neurotransmitters, hormones and enzymes; and lymphocyte activation and proliferation. Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca(2+) mobilizing nucleotide present in many cell types and species, from plants to animals. cADPR is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide. The main ADP-ribosyl cyclase in mammals is CD38, a multi-functional enzyme and a type II membrane protein. It has been shown that many extracellular stimuli can induce cADPR production that leads to calcium release or influx, establishing cADPR as a second messenger. cADPR has been linked to a wide variety of cellular processes, but the molecular mechanisms regarding cADPR signaling remain elusive. The aim of this review is to summarize the CD38/cADPR/Ca(2+) signaling pathway, focusing on the recent advances involving the mechanism and physiological functions of cADPR-mediated Ca(2+) mobilization.