Life cycle assessment of carbonaceous pellets used in blast furnaces in the context of "double carbon".

As the sole carbonaceous renewable energy source, biomass is distinguished by its abundant yield, widespread distribution, and carbon neutrality. It is integral to the achievement of zero and negative carbon production via conventional carbonaceous pellet technology. This study introduces a cradle-to-gate life cycle assessment methodology for biomass preparation in carbonaceous pellets. We prepare high-quality biochar through a process combining hydrothermal carbonization and pyrolytic carbonization. Biomass high molecular weight extracts are obtained via organic pyrolytic extraction, while biomass high-temperature binders result from the modification and treatment of biochar. Biomass carbonaceous pellets are then formed using hot press technology. The ReCiPe model facilitates a comprehensive life cycle assessment of biomass carbonaceous pellets used in blast furnace production. The study leverages two comprehensive evaluation indicators - renewability, and environmental performance - to enhance the environmental performance of the process system and to maximize energy-saving and emission reduction potential.

Complete characterization of the yak testicular development using accurate full-length transcriptome sequencing.

Alternative splicing is a prevalent phenomenon in testicular tissues. Due to the low assembly accuracy of short-read RNA sequencing technology in analyzing post-transcriptional regulatory events, full-length (FL) transcript sequencing is highly demanded to accurately determine FL splicing variants. In this study, we performed FL transcriptome sequencing of testicular tissues from 0.5, 1.5, 2.5, and 4-year-old yaks and 4-year-old cattle-yaks using Oxford Nanopore Technologies. The obtained sequencing data were predicted to have 47,185 open reading frames (ORFs), including 26,630 complete ORFs, detected 7645 fusion transcripts, 15,355 alternative splicing events, 25,798 simple sequence repeats, 7628 transcription factors, and 35,503 long non-coding RNAs. A total of 40,038 novel transcripts were obtained from the sequencing data, and the proportion was almost close to the number of known transcripts identified. Structural analysis and functional annotation of these novel transcripts resulted in the successful annotation of 9568 transcripts, with the highest and lowest annotation numbers in the Nr and KOG databases, respectively. Weighted gene co-expression network analysis revealed the key regulatory pathways and hub genes at various stages of yak testicular development. Our findings enhance our comprehension of transcriptome complexity, contribute to genome annotation refinement, and provide foundational data for further investigations into male sterility in cattle-yaks.

Genetic diversity, phylogeography, and maternal origin of yak (Bos grunniens).

BACKGROUND: There is no consensus as to the origin of the domestic yak (Bos grunniens). Previous studies on yak mitochondria mainly focused on mitochondrial displacement loop (D-loop), a region with low phylogenetic resolution. Here, we analyzed the entire mitochondrial genomes of 509 yaks to obtain greater phylogenetic resolution and a comprehensive picture of geographical diversity. RESULTS: A total of 278 haplotypes were defined in 509 yaks from 21 yak breeds. Among them, 28 haplotypes were shared by different varieties, and 250 haplotypes were unique to specific varieties. The overall haplotype diversity and nucleotide diversity of yak were 0.979 ± 0.0039 and 0.00237 ± 0.00076, respectively. Phylogenetic tree and network analysis showed that yak had three highly differentiated genetic branches with high support rate. The differentiation time of clades I and II were about 0.4328 Ma, and the differentiation time of clades (I and II) and III were 0.5654 Ma. Yushu yak is shared by all haplogroups. Most (94.70%) of the genetic variation occurred within populations, and only 5.30% of the genetic variation occurred between populations. The classification showed that yaks and wild yaks were first clustered together, and yaks were clustered with American bison as a whole. Altitude had the highest impact on the distribution of yaks. CONCLUSIONS: Yaks have high genetic diversity and yak populations have experienced population expansion and lack obvious phylogeographic structure. During the glacial period, yaks had at least three or more glacial refugia.

An insight, at the atomic level, into the structure and catalytic properties of the isomers of the Cu22 cluster.

The study of structural isomerism in copper nanoclusters has been relatively limited compared to that in gold and silver nanoclusters. In this work, we present the controlled synthesis and structures of two isomeric copper nanoclusters, denoted as Cu22-1 and Cu22-2, whose compositions were determined to be Cu22(SePh)10(Se)6(P(Ph-4F)3)8 through single-crystal X-ray diffraction (SCXRD). The structural isomerism of Cu22-1 and Cu22-2 arises from the different arrangements of a few Cu(SeR)(PR3) motifs on the surface structure. These subtle changes in the surface structure also influence the distortion of the core and the spatial arrangement of the clusters, and affect the electronic structure. Furthermore, due to their distinct structures, Cu22-1 and Cu22-2 exhibit different catalytic properties in the copper-catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC). Notably, Cu22-1 demonstrates efficient catalytic activity for photoinduced AAC, achieving a yield of 90% within 1 hour. This research contributes to the understanding of structural isomerism in copper nanoclusters and offers insights into the structure-function relationship in these systems.

Immunotherapeutic value of NUSAP1 associated with bladder cancer through a comprehensive analysis of 33 human cancer cases.

To investigate the correlation between nucleolar spindle-associated protein 1 (NUSAP1) and cancer immunotherapy across 33 different types of human cancers. We conducted an analysis of The Cancer Genome Atlas (TCGA) database to retrieve gene expression data and clinical characteristics for 33 different cancer types. The immunotherapy cohorts encompassed GSE67501, GSE78220, and IMvigor210. Relevant information was extracted from the gene expression repository. We assessed the prognostic significance of NUSAP1 by examining various clinical parameters. The single-sample gene-set enrichment analysis (ssGSEA) method was utilized to gauge NUSAP1 activity and to contrast NUSAP1 transcriptome and protein levels. We delved into the correlation between NUSAP1 and various immune processes and components to gain insights into NUSAP1's role. We also discussed coherent pathways associated with NUSAP1 signal transduction and its impact on immunotherapy biomarkers. To authenticate and validate the differential expression patterns of NUSAP1 in bladder tumor tissues versus normal bladder counterparts, we utilized Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry (IHC) techniques. NUSAP1 exhibits overexpression across a spectrum of malignancies, and its expression levels correlate with overall survival (OS), disease-specific survival, and tumor stage in specific cancer types. Furthermore, NUSAP1 expression is linked to mutations, methylation patterns, and immunotherapy responses in human cancers. Meanwhile, our experiments, involving WB, RT-qPCR, and IHC, consistently demonstrated significantly higher NUSAP1 expression in bladder tumor tissues compared to normal controls. Our study underscores the potential of NUSAP1 as a promising prognostic indicator and immunotherapeutic target for a range of malignant tumors.

Left endoscopic combined intrarenal surgery with electrocoagulation hemostasis and right flexible ureteroscopic lithotripsy for bilateral upper urinary tract stones: a case report.

Background: Percutaneous nephrolithotomy (PCNL) is the first-line treatment for large renal stones. However, multi-tract or staged procedures may be necessitated in bilateral or anatomically-complex stones to achieve stone clearance. Endoscopic combined intrarenal surgery (ECIRS) integrates the advantages of PCNL and retrograde intrarenal surgery. In this article, we detail a hybrid surgical technique adopted for the management of complex simultaneous bilateral upper urinary tract stones. In addition, we discuss the advantages and disadvantages of combining a variety of new techniques that may improve post-operative outcomes and patient satisfaction. Case Description: We report the case of a 36-year-old male with a large left renal pelvis stone, right proximal ureteric stone, and bilateral renal stones. Biochemical results showed raised inflammatory markers but he denied pre-stenting and staged surgery. After receiving 3-day antibiotic prophylaxis, he underwent an elective hybrid procedure. Under split-leg prone position, we performed a hybrid procedure that included left ECIRS with tubeless single-tract mini PCNL and left flexible ureteroscopy, and right flexible ureteroscopic lithotripsy. Hemostasis was achieved by electrocauterization with a novel device. The patient made an uneventful recovery. Follow-up computed tomography (CT) at 1-month revealed complete stone clearance. Conclusions: Unilateral ECIRS with tubeless single-tract mini PCNL with electrocoagulation hemostasis and adjacent retrograde intrarenal surgery in split-leg prone position is a safe, feasible, and efficient technique to manage large renal stones.

Natural product-derived ferroptosis mediators.

It has been 11 years since ferroptosis, a new mode of programmed cell death, was first proposed. Natural products are an important source of drug discovery. In the past five years, natural product-derived ferroptosis regulators have been discovered in an endless stream. Herein, 178 natural products discovered so far to trigger or resist ferroptosis are classified into 6 structural classes based on skeleton type, and the mechanisms of action that have been reported are elaborated upon. If pharmacodynamic data are sufficient, the structure and bioactivity relationship is also presented. This review will provide medicinal chemists with some effective ferroptosis regulators, which will promote the research of natural product-based treatment of ferroptosis-related diseases in the future.

Novel small molecule inhibitors targeting renal cell carcinoma: Status, challenges, future directions.

Renal cell carcinoma (RCC) is the most common renal malignancy with a rapidly increasing morbidity and mortality rate gradually. RCC has a high mortality rate and an extremely poor prognosis. Despite numerous treatment strategies, RCC is resistant to conventional radiotherapy and chemotherapy. In addition, the limited clinical efficacy and inevitable resistance of multiple agents suggest an unmet clinical need. Therefore, there is an urgent need to develop novel anti-RCC candidates. Nowadays many promising results have been achieved with the development of novel small molecule inhibitors against RCC. This paper reviews the recent research progress of novel small molecule inhibitors targeting RCC. It is focusing on the structural optimization process and conformational relationships of small molecule inhibitors, as well as the potential mechanisms and anticancer activities for the treatment of RCC. To provide a theoretical basis for promoting the clinical translation of novel small molecule inhibitors, we discussed their application prospects and future development directions. It could be capable of improving the clinical efficacy of RCC and improving the therapy resistance for RCC.

Do microbial-gut-muscle mediated by SCFAs, microbial-gut-brain axis mediated by insulin simultaneously regulate yak IMF deposition?

Ruminant rumen plays an important role in the digestibility of cellulose, hemicellulose, starch and fat. In this study, the yaks under graze and stall feeding were chosen as the models of different rumen bacteria and intramuscular fat (IMF). The characteristics of IMF deposition, serum indexes in yaks were detected; the bacteria, metabolites in rumen was explored by 16S rRNA sequencing technology, untargeted metabolomics based on liquid chromatography-mass spectrometer and gas chromatography, respectively; the transcriptome of longissimus thoracis was identified by RNA-Sequencing analysis. Based on above results, a hypothesis that yak IMF deposition is regulated by the combined action of microbiome-gut-brain and muscle axis was proposed. The short-chain fatty acids (SCFAs) and neurotransmitters precursors like acetylcholine produced in yak rumen promoted insulin secretion via central nervous system. These insulin resulted in the high expression of SREBF1 gene by gut-brain axis; SCFAs can directly arrive to muscular tissue via blood circulation system, then activated the expression of PPARγ gene by gut-muscle axis. The expression of lipogenesis gene SCD, FABP3, CPT1, FASN and ACC2 was accordingly up-regulated. This study firstly introduce the theory of microbiome-gut-brain/muscle axis into the study of ruminant, and comprehensively expounded the regulatory mechanism of yak IMF deposition.

Exopolysaccharides produced by Antrodia cinnamomea using microparticle-enhanced cultivation: Optimization, primary structure and antibacterial property.

Microparticle-enhanced cultivation was used to enhance the production of exopolysaccharides (EPSs) from Antrodia cinnamomea. The structure and antibacterial activity of two EPSs produced by A. cinnamomea treated with Al2O3 [EPS-Al (crude) and EPS-Al-p (purified)] and without Al2O3 [EPS-C (crude) and EPS-C-p (purified)] were compared. It was observed that the addition of 4 g/L Al2O3 at 0 h resulted in the highest EPS yield of 1.46 g/L, possible attributed to the enhanced permeability of the cell membrane. The structural analysis revealed that EPS-C-p and EPS-Al-p had different structures. EPS-C-p was hyperbranched and spherical with a Mw of 10.8 kDa, while EPS-Al-p was irregular and linear with a Mw of 12.5 kDa. The proportion of Man in EPS-Al-p decreased, while those of Gal and Glc increased when compared to EPS-C-p. The total molar ratios of 6-Glcp and 4-Glcp in EPS-Al-p are 1.45 times that of EPS-C-p. Moreover, EPSs could alter bacterial cell morphology, causing intracellular substance leakage and growth inhibition, with EPS-Al having a stronger antibacterial activity than EPS-C. In conclusion, A. cinnamomea treated with Al2O3 could produce more EPSs, changing monosaccharide composition and glycosidic linkage profile, which could exert stronger antibacterial activity than that produced by untreated A. cinnamomea.

Rare 7,9'-dinorlignans with neuroprotective activity from the roots of Lindera aggregata (Sims) Kosterm.

Linderagatins C-F (1-4), the first examples of naturally occurring diaryltetrahydrofuran-type 7,9'-dinorlignans, were characterized from the roots of Lindera aggregata (Sims) Kosterm. The structures of these dinorlignans were elucidated by extensive spectroscopic analysis. The absolute configurations were determined based on calculated and experimental ECD data. A biosynthetic pathway for these dinorlignans was hypothetically proposed. Compounds 2 and 3 showed significant neuroprotective effects on erastin-induced ferroptosis in HT-22 cells with EC50 values of 23.4 and 21.8 µM, respectively.

Molecular epidemiology and antimicrobial resistance patterns of carbapenem-resistant Acinetobacter baumannii isolates from patients admitted at ICUs of a teaching hospital in Zunyi, China.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a predominant strain of healthcare-associated infections worldwide, particularly in intensive care units (ICUs). Therefore, it is imperative to study the molecular epidemiology of CRAB in the ICUs using multiple molecular typing methods to lay the foundation for the development of infection prevention and control strategies. This study aimed to determine the antimicrobial susceptibility profile, the molecular epidemiology and conduct homology analysis on CRAB strains isolated from ICUs. Methods: The sensitivity to various antimicrobials was determined using the minimum inhibitory concentration (MIC) method, Kirby-Bauer disk diffusion (KBDD), and E-test assays. Resistance genes were identified by polymerase chain reaction (PCR). Molecular typing was performed using multilocus sequence typing (MLST) and multiple-locus variable-number tandem repeat analysis (MLVA). Results: Among the 79 isolates collected, they exhibited high resistance to various antimicrobials but showed low resistance to levofloxacin, trimethoprim-sulfamethoxazole, and tetracyclines. Notably, all isolates of A. baumannii were identified as multidrug-resistant A. baumannii (MDR-AB). The bla OXA-51-like, adeJ, and adeG genes were all detected, while the detection rates of bla OXA-23-like (97.5%), adeB (93.67%), bla ADC (93.67%), qacEΔ1-sul1 (84.81%) were higher; most of the Ambler class A and class B genes were not detected. MLST analysis on the 79 isolates identified five sequence types (STs), which belonged to group 3 clonal complexes 369. ST1145Ox was the most frequently observed ST with a count of 56 out of 79 isolates (70.89%). MLST analysis for non-sensitive tigecycline isolates, which were revealed ST1145Ox and ST1417Ox as well. By using the MLVA assay, the 79 isolates could be grouped into a total of 64 distinct MTs with eleven clusters identified in them. Minimum spanning tree analysis defined seven different MLVA complexes (MCs) labeled MC1 to MC6 along with twenty singletons. The locus MLVA-AB_2396 demonstrated the highest Simpson's diversity index value at 0.829 among all loci tested in this study while also having one of the highest variety of tandem repeat species. Conclusion: The molecular diversity and clonal affinities within the genomes of the CRAB strains were clearly evident, with the identification of ST1144Ox, ST1658Ox, and ST1646Oxqaq representing novel findings.

Exploring Novel Genome Instability-associated lncRNAs and their Potential Function in Pan-Renal Cell Carcinoma.

OBJECTIVE: Genomic instability can drive clonal evolution, continuous modification of tumor genomes, and tumor genomic heterogeneity. The molecular mechanism of genomic instability still needs further investigation. This study aims to identify novel genome instabilityassociated lncRNAs (GI-lncRNAs) and investigate the role of genome instability in pan-Renal cell carcinoma (RCC). MATERIALS AND METHODS: A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation. RESULTS: A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance. CONCLUSIONS: In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms.

A comparative study of flexible ureteroscopic lithotripsy for upper urinary tract stones in patients with prior urosepsis following emergency drainage via retrograde ureteral stent or percutaneous nephrostomy.

BACKGROUND: Patients with urosepsis associated with upper urinary tract stones require further stone management after emergency drainage. OBJECTIVE: To evaluate the safety and efficacy of elective flexible ureteroscopic lithotripsy (F-URSL) for upper urinary tract stones in patients with prior urosepsis who have undergone emergency drainage using retrograde ureteral stent(RUS) or percutaneous nephrostomy (PCN). METHOD: Between January 2017 and December 2021, clinical data were collected for 102 patients who underwent elective F-URSL following emergency drainage for urosepsis caused by upper ureteral or renal stones. The patients were categorized into two groups based on the drainage method used: the RUS group and the PCN group. The collected data included patient demographics, stone parameters, infection recovery after emergency drainage, and clinical outcomes post F-URSL. Subsequently, the data underwent statistical analysis. RESULTS: A total of 102 patients were included in the statistical analysis, with 58 (56.86%) in the RUS group and 44 (43.14%) in the PCN group. Among the patients, 84 (82.35%) were female and 18 (17.65%) were male, with an average age of 59.36 years. Positive urine cultures were observed in 71 (69.61%) patients. Successful drainage was achieved in all patients in both groups, and there were no significant differences in the time required for normalization of white blood cell count (WBC) and body temperature following drainage. Additionally, all patients underwent F-URSL successfully, and no statistically significant differences were observed between the two groups in terms of operative time, stone-free rates, postoperative fever, and postoperative hospital stay. CONCLUSION: Both RUS and PCN have been established as effective approaches for managing urosepsis caused by upper urinary tract stones. Furthermore, the impact of these two drainage methods on the subsequent management of stones through elective F-URSL has shown consistent outcomes.

A multicenter study on the application of artificial intelligence radiological characteristics to predict prognosis after percutaneous nephrolithotomy.

Background: A model to predict preoperative outcomes after percutaneous nephrolithotomy (PCNL) with renal staghorn stones is developed to be an essential preoperative consultation tool. Objective: In this study, we constructed a predictive model for one-time stone clearance after PCNL for renal staghorn calculi, so as to predict the stone clearance rate of patients in one operation, and provide a reference direction for patients and clinicians. Methods: According to the 175 patients with renal staghorn stones undergoing PCNL at two centers, preoperative/postoperative variables were collected. After identifying characteristic variables using PCA analysis to avoid overfitting. A predictive model was developed for preoperative outcomes after PCNL in patients with renal staghorn stones. In addition, we repeatedly cross-validated their model's predictive efficacy and clinical application using data from two different centers. Results: The study included 175 patients from two centers treated with PCNL. We used a training set and an external validation set. Radionics characteristics, deep migration learning, clinical characteristics, and DTL+Rad-signature were successfully constructed using machine learning based on patients' pre/postoperative imaging characteristics and clinical variables using minimum absolute shrinkage and selection operator algorithms. In this study, DTL-Rad signal was found to be the outstanding predictor of stone clearance in patients with renal deer antler-like stones treated by PCNL. The DTL+Rad signature showed good discriminatory ability in both the training and external validation groups with AUC values of 0.871 (95% CI, 0.800-0.942) and 0.744 (95% CI, 0.617-0.871). The decision curve demonstrated the radiographic model's clinical utility and illustrated specificities of 0.935 and 0.806, respectively. Conclusion: We found a prediction model combining imaging characteristics, neural networks, and clinical characteristics can be used as an effective preoperative prediction method.

Connexin43 reduces LPS-induced inflammation in hDPCs through TLR4-NF-κB pathway via hemichannels.

OBJECTIVES: Connexin43 (Cx43) is involved in the inflammation of many tissue types. Dental caries is infectious disease resulting from mineralized tissue dissolution by a specific bacterial population, causing pulp inflammation. However, Cx43's role in dental pulp remains unclear. Here, we investigated the function of Cx43 during pulp inflammation. MATERIALS AND METHODS: We constructed a dentin injury model in Sprague-Dawley rats to investigate changes in Cx43 expression during pulp inflammation. Cx43 was inhibited in human dental pulp cells (hDPCs) that had been stimulated with lipopolysaccharide (LPS) to investigate the effect of Cx43 on inflammatory response. Promotion of TLR4-NF-κB pathway activity and special Cx43 channel inhibitors were used to clarify the function of Cx43 in hDPCs. RESULTS: Dentin injury led to low-level inflammation in dental pulp. Following dentin injury, Cx43 expression initially decreased before gradually recovering to normal levels. Cx43 inhibition reduced LPS-induced expression of inflammatory cytokines and NF-κB pathway activity. Promotion of NF-κB pathway activity counteracted the effect of Cx43 in hDPCs. Furthermore, inhibition of Cx43 hemichannels reduced LPS-induced inflammatory cytokine expression. CONCLUSIONS: Cx43 is involved in inflammation of dental pulp, while its inhibition reduced LPS-induced inflammation in hDPCs through NF-κB pathway via blockage of hemichannels.

Visualizing moiré ferroelectricity via plasmons and nano-photocurrent in graphene/twisted-WSe2 structures.

Ferroelectricity, a spontaneous and reversible electric polarization, is found in certain classes of van der Waals (vdW) materials. The discovery of ferroelectricity in twisted vdW layers provides new opportunities to engineer spatially dependent electric and optical properties associated with the configuration of moiré superlattice domains and the network of domain walls. Here, we employ near-field infrared nano-imaging and nano-photocurrent measurements to study ferroelectricity in minimally twisted WSe2. The ferroelectric domains are visualized through the imaging of the plasmonic response in a graphene monolayer adjacent to the moiré WSe2 bilayers. Specifically, we find that the ferroelectric polarization in moiré domains is imprinted on the plasmonic response of the graphene. Complementary nano-photocurrent measurements demonstrate that the optoelectronic properties of graphene are also modulated by the proximal ferroelectric domains. Our approach represents an alternative strategy for studying moiré ferroelectricity at native length scales and opens promising prospects for (opto)electronic devices.

Transcriptome Studies Reveal the N6-Methyladenosine Differences in Testis of Yaks at Juvenile and Sexual Maturity Stages.

Studying the mechanism of spermatogenesis is key to exploring the reproductive characteristics of male yaks. Although N6-methyladenosine (m6A) RNA modification has been reported to regulate spermatogenesis and reproductive function in mammals, the molecular mechanism of m6A in yak testis development and spermatogenesis remains largely unknown. Therefore, we collected testicular tissue from juvenile and adult yaks and found that the m6A level significantly increased after sexual maturity in yaks. In MeRIP-seq, 1702 hypermethylated peaks and 724 hypomethylated peaks were identified. The hypermethylated differentially methylated RNAs (DMRs) (CIB2, AK1, FOXJ2, PKDREJ, SLC9A3, and TOPAZ1) mainly regulated spermatogenesis. Functional enrichment analysis showed that DMRs were significantly enriched in the adherens junction, gap junction, and Wnt, PI3K, and mTOR signaling pathways, regulating cell development, spermatogenesis, and testicular endocrine function. The functional analysis of differentially expressed genes showed that they were involved in the biological processes of mitosis, meiosis, and flagellated sperm motility during the sexual maturity of yak testis. We also screened the key regulatory factors of testis development and spermatogenesis by combined analysis, which included BRCA1, CREBBP, STAT3, and SMAD4. This study indexed the m6A characteristics of yak testicles at different developmental stages, providing basic data for further research of m6A modification regulating yak testicular development.

Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer.

BACKGROUND: Metformin is the most frequently prescribed medication for the treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety of cancer types. Metformin can inhibit the growth of many cancer cells through various mechanisms, including ferroptosis. However, it is still unclear whether metformin can induce ferroptosis in lung cancer. METHODS: This study evaluated the anti-tumor effect of metformin by detecting the levels of oxidative stress factors, the levels of ferrous ions, and the expression of ferroptosis-related genes in A549 and H1299 lung cancer cell lines treated with or without metformin. RESULTS: The results showed that metformin treatment increased the levels of MDA, ROS and iron ions, while decreased the levels of GSH, T-SOD and CAT. Meanwhile, metformin treatment reduced the protein expression levels of Gpx4 and SLC7A11, Nrf2 and HO-1, while the addition of ferroptosis inhibitor ferrostatin-1 reversed the reduction. CONCLUSIONS: These results demonstrated that metformin exerts anti-tumor effects by inducing ferroptosis through the Nrf2/HO-1 signaling pathway in lung cancer cells, providing a theoretical basis for drug therapy of lung cancer patients.

Single-cell RNA sequencing and UPHLC-MS/MS targeted metabolomics offer new insights into the etiological basis for male cattle-yak sterility.

The variety of species can be efficiently increased by interspecific hybridization. However, because the males in the hybrid progeny are usually sterile, this heterosis cannot be employed when other cattle and yaks are hybridized. While some system-level studies have sought to explore the etiological basis for male cattle-yak sterility, no systematic cellular analyses of this phenomenon have yet been performed. Here, single-cell RNA sequencing and UPHLC-MS/MS targeted metabolomics methods were used to study the differences in testicular tissue between 4-year-old male yak and 4-year-old male cattle-yak, providing new and comprehensive insights into the causes of male cattle-yak sterility. Cattle-yak testes samples detected 6 somatic cell types and one mixed germ cell type. Comparisons of these cell types revealed the more significant differences in Sertoli cells (SCs) and [Leydig cells and myoid cells (LCs_MCs)] between yak and cattle-yak samples compared to other somatic cell clusters. Even though the LCs and MCs from yaks and cattle-yaks were derived from the differentiation of the same progenitor cells, a high degree of overlap between LCs and MCs was observed in yak samples. Still, only a small overlap between LCs and MCs was observed in cattle-yak samples. Functional enrichment analyses revealed that genes down-regulated in cattle-yak SCs were primarily enriched in biological activity, whereas up-regulated genes in these cells were enriched for apoptotic activity. Furthermore, the genes of up-regulated in LCs_MCs of cattle-yak were significantly enriched in enzyme inhibitor and molecular function inhibitor activity. On the other hand, the genes of down-regulated in these cells were enriched for signal receptor binding, molecular function regulation, positive regulation of biological processes, and regulation of cell communication activity. The most significant annotated differences between yak and cattle-yak LCs_MCs were associated with cell-to-cell communication. While yak LCs_MCs regulated spermatogenic cells at spermatogonia, spermatocyte, and spermatid levels, no such relationships were found between cattle-yak LCs_MCs and germ cells. This may suggest that the somatic niche in male cattle-yak testes is a microenvironment that is ultimately not favorable for spermatogenesis.