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Abstract With the continuous development of underground engineering construction in China, it is particularly important to study the identification of structural plane characteristics of rock masses. In this study, three types of pseudo-rock specimens with structural plane interlayers were fabricated to analyze the patterns of drilling parameter changes in rock bodies with structural planes during the drilling process and to explore the characterization and identification methods of rock body structural planes. Gneiss, granite, and sandstone were used as rock materials, with gypsum mortar as the interlayer material for the structural planes in these three types of specimens. The indoor digital drilling equipment was utilized for conducting indoor digital drilling experiments. The variation patterns of drilling parameters in rock bodies with structural surfaces under different interlayer inclinations and thicknesses were analyzed. The relationship between the ratio of the change in rotational speed and drilling speed during the stable phase of the upper rock mass and the peak torque and peak drilling pressure has been established. The relationship between the structural plane inclination angle and the ratio of change in rotational speed and drilling speed has been determined. By utilizing the variation in these ratios, the impacts of the structural plane inclination angle and the thickness of the structural plane on the peak torque and peak drilling pressure have been elucidated. The research results provide a theoretical basis for the stability evaluation of rock masses with structural planes under drilling action.

Abstract Background Saccharomyces cerevisiae has been considered a harmless yeast, but in recent years, increasing evidence has shown that it can cause disease in humans, especially invasive infections in infants/children and vulvovaginal infections in women. This study aimed to investigate the clinical information and antifungal susceptibility of clinical cases with S. cerevisiae and establish a foundation for the prevention and treatment of fungal infections. Methods This study was conducted from May 2018 to May 2023 at a national regional medical center in Southwest China for women and children. The demographic and clinical characteristics of patients isolated with S. cerevisiae were collected and analyzed. All the isolates were cultured on Sabouraud medium plates and identified by MALDI-TOF MS. The antifungal susceptibility of S. cerevisiae to 10 agents (amphotericin B, fluconazole, itraconazole, voriconazole, micafungin, caspofungin, terbinafine and 5-flucytosine) was determined via the microdilution broth method to determine the minimum inhibitory concentrations (MICs). Results A total of 75 cases of S. cerevisiae isolated from patients with vulvovaginal candidiasis (VVC, 44 cases), pneumonia (13 cases), or diarrhea (18 cases) were included after data review. The MICs of voriconazole and flucytosine for S. cerevisiae isolated from different body sites differed, with higher resistance in intestinal isolates. In this study, S. cerevisiae caused VVC, but there was no clear evidence that it was involved in pneumonia or diarrhea. Compared with those of Candida albicans, the primary pathogen of VVC, the MICs of fluconazole (11.96 ± 5.78 µg/mL vs. 67.64 ± 16.62 µg/mL, p = 0.002), itraconazole (0.77 ± 0.19 µg/mL vs. 2.31 ± 0.53 µg/mL, p = 0.008), voriconazole (0.22 ± 0.09 µg/mL vs. 5.02 ± 1.09 µg/mL, p

Abstract In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.

The use of support structures with good explosion resistance to support and reinforce underground projects has become a focus of concern for relevant units in order to ensure the safety of underground projects in explosive ground loads. The blast resistance of underground caverns and the influence of support parameters on blast resistance have been studied when lining and pre-stressing anchors are supported individually under dynamic and static coupling. Straight-walled arched caverns are chosen for this study because of their strong blast resistance. The influence of excavation unloading on the support structure was analyzed under the condition of a burial depth of 500 m. The study investigated the blast resistance of caves supported solely by singular concrete lining support and singular pre-stressed anchor bolt support. The research findings indicate that pre-stressed anchor bolts significantly limit the deformation capacity of surrounding rock while lining is more effective in restricting the vibration response of surrounding rock. The pre-stressed anchor bolts ensure operation within the strength range throughout the entire process with no alteration in load-bearing capacity. Increasing the thickness of the lining can reduce the vibration response of the cavern. Meanwhile, enhancing the pre-stressed anchor bolts within a certain range notably restricts the deformation response of the cavern. Therefore, the pre-stressed anchor bolts should be employed as the supporting structure to bear the excavation and unloading loads of the cavern.

Jerusalem artichoke juice is valued for its nutritional content and health benefits. Spontaneous fermentation enhances its flavor, quality, and functional components through microbial metabolic activities. This study used high-throughput sequencing to analyze microbial community changes, and LC–MS and GC–MS to detect secondary metabolites and flavor compounds during fermentation. During natural fermentation, beneficial bacteria like Lactobacillus and Pediococcus increased, promoting lactic acid production and inhibiting harmful bacteria, while environmental bacteria decreased. Similarly, fungi shifted from environmental types like Geosmithia and Alternaria to fermentation-associated Pichia and Penicillium. A total of 1666 secondary metabolites were identified, with 595 upregulated and 497 downregulated. Key metabolic pathways included phenylpropanoid biosynthesis, with significant increases in phenylalanine, tryptophan, and related metabolites. Lipid and nucleotide metabolism also showed significant changes. Flavor compounds, including 134 identified alcohols, esters, acids, and ketones, mostly increased in content after fermentation. Notable increases were seen in Phenylethyl Alcohol, Ethyl Benzenepropanoate, 3-Methylbutyl Butanoate, Ethyl 4-Methylpentanoate, 5-Ethyl-3-Hydroxy-4-Methyl-2(5H)-Furanone, Ethyl Decanoate, Hexanoic Acid, and 1-Octanol. γ-aminobutyric acid (GABA) and other functional components enhanced the health value of the juice. This study provides insights into microbial and metabolic changes during fermentation, aiding in optimizing processes and improving the quality of fermented Jerusalem artichoke juice for functional food development.

IntroductionResearch on the outdoor thermal comfort (OTC) of a university campus is beneficial to the physical and mental health of college students.MethodsIn this study, the OTC of students attending Tibet University in Lhasa, which experiences high-altitude cold climate conditions, under different activity intensities was studied using field measurements and a questionnaire survey.ResultsWith the increase in activity intensity, the comfort physiologically equivalent temperature (PET) value gradually increased in summer, while the comfortable PET value gradually decreased in winter. The most comfortable PET value is 17.6°C in summer and 11.5°C in winter. The neutral PET of Tibetan college students during outdoor activities in summer was 16.3°C, and the neutral PET of outdoor activities in winter was 12.1°C. Gender and ethnicity had different effects on thermal sensation under different activity intensities. Under vigorous-intensity activities, PET in winter and summer had the greatest influence on thermal sensation. The situation was different under moderate-intensity activity. PET had the greatest influence on thermal sensation in summer, and Tmrt had the greatest influence on thermal sensation in winter.DiscussionThese findings provide a basis for an improved design of the outdoor environment under different outdoor activity intensities in high-altitude areas.

The muscarinic acetylcholine receptor M3 (M3-mAChR) is involved in various physiological and pathological processes. Owing to specific cardioprotective effects, M3-mAChR is an ideal diagnostic and therapeutic biomarker for cardiovascular diseases (CVDs). Growing evidence has linked M3-mAChR to the development of multiple CVDs, in which it plays a role in cardiac protection such as anti-arrhythmia, anti-hypertrophy, and anti-fibrosis. This review summarizes M3-mAChR’s expression patterns, functions, and underlying mechanisms of action in CVDs, especially in ischemia/reperfusion injury, cardiac hypertrophy, and heart failure, opening up a new research direction for the treatment of CVDs.

The northern margin of the North China Craton is one of the most important porphyry-skarn molybdenum ore belts in the world. The eastern Hebei Province, which contains a high number of molybdenum and gold (molybdenum) resources, is an important portion of the northern margin of the North China Craton. Xichanggou and Huashi, located in eastern Hebei, are quartz-molybdenum vein deposits that are intimately associated with intrusions that are deeply concealed in the mining area. This work presents two zircon U-Pb dates and ten molybdenite Re-Os ages from samples of the aforementioned two deposits in order to determine the timing of the intrusion and mineralization. The zircon U-Pb ages of the quartz monzonite porphyry from Xichanggou are determined to be 163.3 ± 0.3 Ma and 162.8 ± 0.4 Ma. The molybdenite Re-Os dating yielded ages of 160.3 ± 4.6 Ma for Xichanggou and 171.4 ± 19 Ma for Huashi, respectively. The isotopic composition of oxygen and hydrogen of the ore-forming fluid from Huashi, as indicated by the δDV-SMOW values (−80.0‰ to −67.6‰) and δ18OH2O values (−1.86‰ to 2.33‰), suggests that the fluid is primarily composed of water derived from magma, with some contribution from atmospheric precipitation. The sulfur isotope values (δ34S) of sulfides from Xichanggou range from 6.5‰ to 7.1‰, while the δ34S values from Huashi range from 3.3‰ to 4.9‰. The lead isotope ratios (206Pb/204Pb and 207Pb/204Pb) of sulfides from Xichanggou and Huashi average at 17.414, 15.428, and 17.591, 15.379, respectively. The Re-Os isotopic compositions of ore sulfides mostly fall within the range of 318 ppm to 50,114 ppm. These isotopic compositions indicate that the materials responsible for the formation of the ores in Xichanggou and Huashi primarily originate from the melting of lower crust materials that have been contaminated by the mantle. Based on the regional data, the molybdenum deposits in eastern Hebei were formed in multiple periods, specifically approximately 170 Ma and 160 Ma in Huahsi and Xichanggou, respectively. The subduction of the Paleo-Pacific plate during the middle–late Jurassic period led to the partial remelting of lower crust material, resulting in the acquisition of a significant quantity of metal elements (Mo), which were subsequently deposited.

Wide-bandgap (WB) mixed-halide perovskite solar cells (PSCs) play a crucial role in perovskite-based tandem solar cells (TSCs), enabling them to exceed the Shockley–Queisser limits of single-junction solar cells. Nonetheless, the lack of stability in WB perovskite films due to photoinduced phase segregation undermines the stability of WB PSCs and their TSCs, thus impeding the commercialization of perovskite-based TSCs. Many efforts have been made to suppress photoinduced phase segregation in WB perovskite films and significant progresses have been obtained. In this review, we elaborate the mechanisms behind photoinduced phase segregation and its impact on the photovoltaic performance and stability of devices. The importance role of advanced characterization techniques in confirming the photoinduced phase segregation are comprehensively summarized. Beyond that, the effective strategies to alleviate photoinduced phase segregation in WB mixed halide PSCs are systematically assessed. Finally, the prospects for developing highly efficient and stable WB PSCs in tandem application are also presented.

Abstract Background The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Methods The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. Results Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. Conclusions CD8+ T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

Fast and accurate prediction for mechanical parameters of rock mass is an important prerequisite for guiding the safe construction of rock engineering. At present, the rock strength parameters test requires well-prepared samples; sample preparation is time consuming, costly, and difficult as well as destructive, in particular the polishing and rectification of the sample ends. In this paper, the mathematical model of the drilling process is established based on the force characteristics of the drill bit and the principle of mechanical limit equilibrium. The digital drilling tests are carried out on four types of rocks to drilling characteristics using the digital drilling system. The concept of cutting strength ratio is proposed to analyze the correlation between cutting strength ratio and rock internal friction angle and cohesion. A new method is proposed for determining the compressive and tensile strength of rock. The results show that the cutting strength ratio increases with the increasing of internal friction angle and cohesion. The uniaxial compressive strength and tensile strength of rock increase linearly with the cutting strength ratio. The average error of rock tensile strength is 12.29%, and the average error of uniaxial compressive strength is 20.44%. The internal friction angle of rock obtained based on the digital drilling technology is consistent with the value measured by the laboratory standard test. This method can provide a new way to determine rock strength parameters in real time.

The interaction between the drill bit and rock is a complex dynamic problem in the process of drilling and breaking rock. In this paper, the dynamic process of drilling and breaking rock is analyzed using ABAQUS software. The rock-breaking mechanism of drilling is revealed according to the stress–strain state of the rock and the force of the drill bit. The effect of the size of the drill bit and the characteristics of the rock mass on the drilling parameters is studied during the drilling process. The results show that both thrust force and torque show a linear increase with the increasing drilling speed under each fixed rotational speed. The drill bit size has minimal impact on the correlation coefficient of the relationship curves between thrust force, torque, and rotation speed. The drilling results in a soft–hard interlayered rock formation show that there are significant differences in thrust force and torque during the drilling process of different rock types. Whether transitioning from a soft rock layer to a hard rock layer or vice versa, the relationship between thrust force and torque is distinctly manifested whenever there is a change in rock quality. The thrust force and torque increase correspondingly with the increase in confining pressure. When subjected to lateral pressure, thrust force and torque gradually increase with the rising confining pressure. Vertical drilling exhibits a larger increase in thrust force and torque compared to horizontal drilling. The thrust force and torque increase more significantly with the rise in confining pressure compared to lateral pressure.

Abstract Despite extensive study, the bandgap characteristics of lead halide perovskites are not well understood. Usually, these materials are considered as direct bandgap semiconductors, while their photoluminescence quantum yield (PLQY) is very low in the solid state or single crystal (SC) state. Some researchers have noted a weak indirect bandgap below the direct bandgap transition in these perovskites. Herein, application of pressure to a CsPbBr3 SC and first‐principles calculations reveal that the nature of the bandgap becomes more direct at a relatively low pressure due to decreased dynamic Rashba splitting. This effect results in a dramatic PLQY improvement, improved more than 90 times, which overturns the traditional concept that the PLQY of lead halide perovskite SC cannot exceed 10%. Application of higher pressure transformed the CsPbBr3 SC into a pure indirect bandgap phase, which can be maintained at near‐ambient pressure. It is thus proved that lead halide perovskites can induce a phase transition between direct and indirect bandgaps. In addition, distinct piezochromism is observed for a perovskite SC for the first time. This work provides a novel framework to understand the optoelectronic properties of these important materials.

Abstract The interface between the perovskite layer and the hole transport layer (HTL) plays a vital role in hole extraction and electron blocking in perovskite solar cells (PSCs), and it is particularly susceptible to harmful defects. Surface passivation is an effective strategy for addressing the above concerns. However, because of its strong polarity, isopropyl alcohol (IPA) is used as a solvent in all of the surface treatment materials reported thus far, and it frequently damages the surface of perovskite. In this paper, a method is proposed for dissolving the passivation materials, for example, guanidine bromide (GABr), in mixed solvents (1:1) of IPA and toluene (TL), which can efficiently passivate interface and grain boundary defects by minimizing the IPA solubility of the perovskite surface. As a result, all the performance parameters Voc, Jsc, and FF are improved, and the power conversion efficiency (PCE) increased from 20.1 to 22.7%. Moreover, combining the PSCs with GABr post‐treatment in mixed solvents with copper indium gallium selenide (CIGS) solar cells, a 4‐terminal (4T) perovskite/CIGS tandem device is realized and a PCE of 25.5% is achieved. The mixed solvent passivation strategy demonstrated here, hopefully, will open new avenues for improving PSCs’ efficiency and stability.

The small PWR has been paid more and more attention due to its diversity of application and flexibility in the site selection. However, the large core power density, the small containment space and the rapid accident progress characteristics make it difficult to control the containment pressure like the traditional PWR during the LOCA. The pressure suppression system has been used by the BWR since the early design, which is a suitable technique that can be applied to the small PWR. Since the configuration and operating conditions are different from the BWR, the pressure suppression system should be redesigned for the small PWR. Conducting the experiments on the scale down test facility is a good choice to reproduce the prototypical phenomena in the test facility, which is both economical and reasonable. A systematic scaling method referring to the H2TS method was proposed to determine the geometrical and thermohydraulic parameters of the pressure suppression containment response test facility for the small PWR conceptual design. The containment and the pressure suppression system related thermohydraulic phenomena were analyzed with top-down and bottom-up scaling methods. A set of the scaling criteria were obtained, through which the main parameters of the test facility can be determined.

Abstract Background Function genomic studies will generally result in lists of genes that may provide clues for exploring biological questions and discovering unanticipated functions, based on differential gene expression analysis, differential epigenomic analysis or co-expression network analysis. While tools have been developed to identify biological functions that are enriched in the genes sets, there remains a need for comprehensive tools that identify functional enrichment of genes for both model and non-model species from a different function classification perspective. Results We developed AllEnricher, a tool that calculates gene set function enrichment, with user-defined updatable libraries backing up for both model and non-model species as well as providing comprehensive functional interpretation from multiple dimensions, including GO, KEGG, Reactome, DO and DisGeNET. Conclusions AllEnricher incorporates up to date information from different public resources and provides a comprehensive resolution for biologists to make sense out of specific gene sets, making it an advanced open-source tool for gene set function analysis.

The Jinzhuping and Changkeng granites are related to the Helong W–Sn ore field in southern Jiangxi Province, China. Three different phases can be found in the Jinzhuping pluton, and their LA-ICP-MS zircon U–Pb ages are 155.2 ± 0.68 Ma, 154.0 ± 0.56 Ma, and 153.4 ± 0.99 Ma, respectively, indicating two types of granitic rocks. All granites in the Helong ore field have similar geochemical characteristics, they have high contents of SiO2 (73.99 wt.%–77.68 wt.%), and total alkali (7.56 wt.%–8.76 wt.%) and are weakly to strongly peraluminous. They are slightly enriched in HREE and depleted in Eu, Ba, Sr, P, and Ti. Zircon εHf(t) values of the Jinzhuping three granites are from −14.4 to −10.4, from −15.3 to −11.4, and from −18.1 to −10.5, and the Hf TDM model ages range from 1.83 to 2.06 Ga, from 1.89 to 2.14 Ga, and from 1.83 to 2.31 Ga, respectively. Whole-rock geochemistry and Hf isotope analysis indicate that the Helong granites experienced a high degree of differentiation and evolution derived by partial melting of the Late Paleoproterozoic crustal materials, and they formed in a backarc caused by low-angle subduction of the Paleopacific plate.

Pressure suppression containment has been adopted extensively in boiling water reactor design due to its remarkable pressure suppression capacity. To study the pressure response characteristics of the containment in the initial stage of the loss-of-coolant accident, it is necessary to build a scaling facility to simulate the prototype. Analysis of the steam mass and energy that are released from the break as well as of the steam condensation that occurs in the suppression pool is conducted, respectively, for the prototype pressurized water reactor. The suppression pipe system resistance is also scaled with a certain ratio. The length and diameter of the main pipe and the branch pipe as well as the orifice diameter are calculated. At last, the prototype and the experimental facility are modeled by MELCOR to analyze the steam mass and energy release. The results show that the containment pressure evolution trends of the prototype and the scaled experimental facility are consistent. The pressure difference exists at some times, with a maximum relative error of 4%.

Cr(VI) is considered as a priority pollutant, and its remediation has attracted increasing attention in the environmental area. In this study, the driving of pyrite-based Cr(VI) reduction by Acidithiobacillus ferrooxidans was systematically investigated. The results showed that pyrite-based Cr(VI) reduction was a highly proton-dependent process and that pH influenced the biological activity. The passivation effect became more significant with an increase in pH, and there was a decrease in Cr(VI) reduction efficiency. However, Cr(VI) reduction efficiency was enhanced by inoculation with A. ferrooxidans. The highest reduction efficiency was achieved in the biological system with a pH range of 1–1.5. Pyrite dissolution and reactive site regeneration were promoted by A. ferrooxidans, which resulted in the enhanced effect in Cr(VI) reduction. The low linear relevancy between pH and Cr(VI) dosage in the biological system indicated a complex interaction between bacteria and pyrite. Secondary iron mineral formation in an unfavorable pH environment inhibited pyrite dissolution, but the passivation effect was relieved under the activity of A. ferrooxidans due to S/Fe oxidization. The balance between Cr(VI) reduction and biological activity was critical for sustainable Cr(VI) reduction. Pyrite-based Cr(VI) remediation driven by chemoautotrophic acidophilic bacteria is shown to be an economical and efficient method of Cr(VI) reduction.

BACKGROUND:Temperature is a key factor influencing the growth and distribution of Taxus chinensis var. mairei, which is of high medicinal value. However, there is little information about the changes in rhizosphere bacterial community of Taxus chinensis var. maire under different temperatures. METHODS:In this study, the rhizosphere bacterial communities of Taxus chinensis var. maire under a series of temperatures [5°C (T5), 15°C (T15), 25°C (T25), 35°C (T35)] were assessed through high-throughput sequencing. And some taxa annotated as Mitochondria were positively correlated with the activity of SOD. RESULTS:Activity of peroxidase (POD) and superoxide dismutase (SOD) were increased and decreased respectively with increasing incubation temperature, showing that SOD may be the dominant reactive oxygen species (ROS) detoxifying enzyme in Taxus chinensis var. maire under low temperature. Taxus chinensis var. maire enriched specific bacterial taxa in rhizosphere under different temperature, and the rhizosphere bacterial diversity decreased with increasing temperature. CONCLUSION:The results indicated that rhizosphere bacteria may play important role for Taxus chinensis var. maire in coping with temperature changes, and the management of rhizosphere bacteria in a potential way to increase the cold resistance of Taxus chinensis var. mairei, thus improving its growth under low temperature and enlarging its habitats.

In this paper, pattern synthesis through time-modulated linear array is studied, and a novel strategy for harmonic beamforming in time-modulated array is proposed. The peak side lobe level is designed as optimization objective function, and the switch-on time sequence of each element is selected as optimization variable. An improved invasive weed optimization (IWO) algorithm is developed in order to determine the optimal parameters describing the pulse sequence used to modulate the excitation weights of array elements. Representative results are reported and discussed to point out potentialities and advantages of the proposed approach, which can obtain lower objective function values.

It is widely known that bioleaching microorganisms have to cope with the complex extreme environment in which microbial ecology relating to community structure and function varies across environmental types. However, analyses of microbial ecology of bioleaching bacteria is still a challenge. To address this challenge, numerous technologies have been developed. In recent years, high-throughput sequencing technologies enabling comprehensive sequencing analysis of cellular RNA and DNA within the reach of most laboratories have been added to the toolbox of microbial ecology. The next-generation sequencing technology allowing processing DNA sequences can produce available draft genomic sequences of more bioleaching bacteria, which provides the opportunity to predict models of genetic and metabolic potential of bioleaching bacteria and ultimately deepens our understanding of bioleaching microorganism. High-throughput sequencing that focuses on targeted phylogenetic marker 16S rRNA has been effectively applied to characterize the community diversity in an ore leaching environment. RNA-seq, another application of high-throughput sequencing to profile RNA, can be for both mapping and quantifying transcriptome and has demonstrated a high efficiency in quantifying the changing expression level of each transcript under different conditions. It has been demonstrated as a powerful tool for dissecting the relationship between genotype and phenotype, leading to interpreting functional elements of the genome and revealing molecular mechanisms of adaption. This review aims to describe the high-throughput sequencing approach for bioleaching environmental microorganisms, particularly focusing on its application associated with challenges.

Correct specification of the left-right (L-R) axis is important for organ morphogenesis. Conserved mechanisms involving cilia rotation inside node-like structures and asymmetric Nodal signaling in the lateral plate mesoderm (LPM), which are important symmetry-breaking events, have been intensively studied. In zebrafish, the clustering and migration of dorsal forerunner cells (DFCs) is critical for the formation of the Kuppfer's vesicle (KV). However, molecular events underlying DFC clustering and migration are less understood. The WD-repeat proteins function in a variety of biological processes, including cytoskeleton assembly, intracellular trafficking, mRNA splicing, transcriptional regulation and cell migration. However, little is known about the function of WD-repeat proteins in L-R asymmetry determination. Here, we report the identification and functional analyses of zebrafish wdr18, a novel gene that encodes a WD-repeat protein that is highly conserved among vertebrate species. wdr18 was identified from a Tol2 transposon-mediated enhancer trap screen. Follow-up analysis of wdr18 mRNA expression showed that it was detected in DFCs or the KV progenitor cells and later in the KV at early somitogenesis stages. Morpholino knockdown of wdr18 resulted in laterality defects in the visceral organs, which were preceded by the mis-expression of Nodal-related genes, including spaw and pitx2. Examination of morphants at earlier stages revealed that the KV had fewer and shorter cilia which are immotile and a smaller cavity. We further investigated the organization of DFCs in wdr18 morphant embryos using ntl and sox17 as specific markers and found that the clustering and migration of DFC was altered, leading to a disorganized KV. Finally, through a combination of wdr18 and itgb1b morpholino injections, we provided evidence that wdr18 and itgb1b genetically interact in the laterality determination process. Thus, we reveal a new and essential role for WD-repeat proteins in the determination and regulation of L-R asymmetry and propose a potential mechanism for wdr18 in the regulation of DFC clustering and migration and KV formation.

Taohong Siwu Decoction (THSWD), a traditional Chinese prescription renowned for its efficacy in promoting blood circulation and alleviating blood stasis, was investigated in this study to delineate its potential active components and discern the core targets (CTs) and signaling pathways implicated in the treatment of Alzheimer's disease (AD). Initially, 25 active compounds (ACs) and 478 corresponding active ingredient targets (AITs) of THSWD were meticulously identified by scrutinizing the active ingredients and their targets through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Similarity Ensemble Approach (SEA) databases. Subsequently, a comprehensive compilation of 724 AD-related targets was assembled from the Therapeutic Target Database (TTD), DisGeNET, DrugBank, Genetic Association Database (GAD), and GeneCards databases. Through a meticulous alignment of AITs with disease-related targets, 64 overlapping targets (OTs) emerged as critical intersections. To distill the key compounds, an intricate analysis of the interrelationships among the 25 ACs and 64 OTs resulted in the identification of 21 first-level key compounds (FKCs). Further scrutiny through protein-protein interaction (PPI) analysis of the 64 OTs revealed 33 CTs. KEGG cluster analysis of these CTs yielded the top 73 pathways, forming the basis for constructing a network diagram encompassing "21 FKCs-33 CTs-73 pathways" using Cytoscape 3.7.2 software. Refining the network through the selection of topological parameters led to the identification of 19 second key components (SKCs). This information was then employed to construct a refined network, "19 SKCs-33 CTs-73 pathways", providing deeper insights into the intricate connections within the system. Further analyses culminated in the creation of a comprehensive network map, encapsulating "6 single drugs-8 potential active ingredients-13 core targets-54 signaling pathways", elucidating the multifaceted intervention of THSWD in AD. These results offered a novel perspective for understanding the pharmacodynamic material basis of THSWD and paved the way for in-depth investigations into its mechanisms of action and clinical applications in the context of AD. [ABSTRACT FROM AUTHOR]

As a progressive neurological disorder, Parkinson's disease (PD) is characterized by tremors and slow movement. Mitochondrial dysfunction and amino acid (AA) metabolism are essential mechanisms of PD. Previous work has confirmed that the changes in amino acid contents in SH-SY5Y cells are earlier than the changes in cell viability. In the present study, we aimed to investigate whether Taohong Siwu dispensing granules (THSWDG) could alleviate rotenone-induced SH-SY5Y cytotoxicity by improving mitochondrial dysfunction and amino acid metabolism disorder. MTT assay was used to analyze the cell viability. JC-1 dye assay was used to measure mitochondrial membrane potential (MMP). HPLC was used to determine the content of amino acids (AAs) in SH-SY5Y cells. Principal component analysis was used to analyze the changes in the content of AAs. In order to further explore the PD-related biological functions involved in amino acid regulation, bioinformatics analysis tools were used to assess the biological processes involved in these protective effects. This study showed that the changes in AA contents in SH-SY5Y cells were earlier than the changes in cell activity. THSWDG dramatically increased cell viability and improved the rotenone-induced repression of MMP and abnormal metabolism of AAs. The results of the bioinformatic analysis suggested that the effects of THSWDG involved nine biological processes, including five AA metabolism regulations related to PD and four biological processes related to oxidative damage. The cellular AA process is a common biological process involved in the regulation of AA metabolism and oxidative damage. These results suggested that THSWDG exerted a cytoprotective effect on SH-SY5Y cells by rescuing mitochondrial dysfunction and AA metabolism disarrangements. [ABSTRACT FROM AUTHOR]

The random fiber laser (RFL) has been an excellent platform for exploring novel optical dynamics and developing new functional optoelectronic devices. However, it is challenging for RFLs to regulate their emission into regular narrow pulses due to their intrinsic randomness. Here, through engineering the laser configuration (cavity Q value, gain distribution and nonlinearity), we demonstrate that narrow (~2.5 ns) pulses with record peak power as high as 64.3 kW are achieved from a self-Q-switched random ytterbium fiber laser. Based on high intracavity intensity and efficient interplay of multiple nonlinear processes (stimulated Brillouin scattering, stimulated Raman scattering and four-wave mixing), an over-one-octave visible-near-infrared (NIR) Raman-frequency comb is generated from single-mode silica fibers for the first time. After spectrally filtering the Raman peaks, wavelength-tunable pulses with durations of several hundreds of picoseconds are obtained. Such a high-peak-power random Q-switched fiber laser and wide frequency comb in the visible-NIR region can find applications in diverse areas, such as spectroscopy, biomedical imaging and quantum information. [ABSTRACT FROM AUTHOR]