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As a crucial component of the climate system, snow cover plays an important role on surface energy budgets, hydrological cycles and socioeconomic development. This paper investigated the spatiotemporal patterns of snow depth across the Qinghai Plateau (QP) during 1980–2018 based on passive microwave (PMW) satellite observation and reanalysis products. The study identified the relationships between the changes in PMW snow depth and topographic features and revealed the impact of climatic variables (air temperature, precipitation and wind speed) and large‐scale atmospheric circulations on observed snow depth variability. The results show that the spatial pattern of snow depth climatology is similar in all datasets, except in terms of magnitude, with high values in the southern and southeastern parts of the QP and low values in the eastern and northwestern parts. Average snow depth correlates positively with precipitation, elevation and slope, and negatively with air temperature and wind speed. The long‐term trends in snow depth vary with the season and the datasets. The PMW snow depth across the QP shows a significant annual (−0.125 cm·decades−1, p <.10) and spring (−0.184 cm·decades−1, p <.05) negative trend, while snow depth for ERA5 and MERRA2 does not present significant trends. Air temperature dominates total snow depth variation over the QP, explaining 43.85, 24.88 and 47.28% of annual, winter and spring PMW snow depth variations, which significantly affects snow depth variations in most parts of the QP, yet the effects of precipitation and wind speed on snow depth variation exhibit significant regional differences, and atmospheric circulations (e.g., AMO) also have a remarkable controlling effect on some localized areas. [ABSTRACT FROM AUTHOR]

Tuberculosis, caused by mycobacteria, continues to pose a substantial public health threat. Mycobacteria typically use cholesterol from the membranes of host macrophages as a carbon and energy source. Most genes that control cholesterol degradation are regulated by KstR, which is highly conserved in Mycobacterium tuberculosis and Mycobacterium smegmatis. Through bioinformatic analysis, we found a typical global nitrogen regulator (GlnR)‐binding motif (CCGAC‐AACAGT‐GACAC) in the promoter region of kstR of M. smegmatis, and we determined its binding activity in vitro using electrophoretic mobility shift assays. Using RT‐qPCR, we found that nine genes involved in side‐chain or sterol‐ring oxidation were upregulated in a ΔglnR M. smegmatis strain compared to the WT strain and glnR‐complemented strains under nitrogen limitation. ATP assays in macrophages revealed that coordinated GlnR–KstR regulation significantly reduced the viability of M. smegmatis in macrophages. Thus, we found that various genes involved in cholesterol catabolism are regulated by GlnR via KstR in response to environmental nitrogen, and that they further affect the invasive ability of M. smegmatis. These findings revealed a novel regulatory mechanism of cholesterol catabolism, which may be useful in the development of new strategies for controlling tuberculosis. [ABSTRACT FROM AUTHOR]

How to realize the ecological protection and high‐quality development (HQD) of the Yellow River Basin (YRB) has become a great challenge for China. Based on panel data from 100 prefecture‐level cities in the YRB from 2006 to 2018, this innovative paper employs the System Generalized Method of Moments (SYS‐GMM) panel model and takes environmental regulation as a situational factor to empirically examine the influence mechanism of industrial agglomeration on HQD in the YRB. Our findings reveal that: (i) overall, a "U‐shaped" relationship exists between industrial agglomeration and HQD in the YRB, and environmental regulation plays a vital role in augmenting their relationship. (ii) Presently, the industrial agglomeration degree prevails on the left side of the threshold value, and the upsurge of industrial agglomeration degree still limits HQD. (iii) From the perspective of river basins, the influence of industrial agglomeration on HQD in the upstream is not significant, and the strengthening effect of environmental regulation is not noticeable. We find a "U‐shaped" relationship between industrial agglomeration and HQD in the midstream, along with notable differences in the correlation between industrial agglomeration and different dimensions of HQD in downstream. This paper helps in further understanding the influence of industrial agglomeration, environmental regulation, and HQD, as well as establishes efficient policies to promote HQD in the YRB and other similar river basins through industrial agglomeration in the context of environmental constraints. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a clinically heterogeneous disorder. Its mechanism is still unknown. Although the altered intersubject variability in functional connectivity (IVFC) within gray‐matter has been reported in MDD, the alterations to IVFC within white‐matter (WM‐IVFC) remain unknown. Based on the resting‐state functional MRI data of discovery (145 MDD patients and 119 healthy controls [HCs]) and validation cohorts (54 MDD patients, and 78 HCs), we compared the WM‐IVFC between the two groups. We further assessed the meta‐analytic cognitive functions related to the alterations. The discriminant WM‐IVFC values were used to classify MDD patients and predict clinical symptoms in patients. In combination with the Allen Human Brain Atlas, transcriptome‐neuroimaging association analyses were further conducted to investigate gene expression profiles associated with WM‐IVFC alterations in MDD, followed by a set of gene functional characteristic analyses. We found extensive WM‐IVFC alterations in MDD compared to HCs, which were associated with multiple behavioral domains, including sensorimotor processes and higher‐order functions. The discriminant WM‐IVFC could not only effectively distinguish MDD patients from HCs with an area under curve ranging from 0.889 to 0.901 across three classifiers, but significantly predict depression severity (r = 0.575, p = 0.002) and suicide risk (r = 0.384, p = 0.040) in patients. Furthermore, the variability‐related genes were enriched for synapse, neuronal system, and ion channel, and predominantly expressed in excitatory and inhibitory neurons. Our results obtained good reproducibility in the validation cohort. These findings revealed intersubject functional variability changes of brain WM in MDD and its linkage with gene expression profiles, providing potential implications for understanding the high clinical heterogeneity of MDD. [ABSTRACT FROM AUTHOR]

Clinical evidence shows that the mechanical stimulation obtained from occlusion could enhance periodontal ligament (PDL) remodeling. Mechano‐growth factor (MGF) is a growth factor produced specifically following mechanical stimulus Here, we aim to investigate the mechanical enhancement potential and mechanism of the MGF in PDL regeneration. In vivo study found that MGF produced from the PDL under occlusion force could strongly enhance PDL remodeling. In vitro experiments and mathematical modeling further confirmed the mechanical enhancement effect of MGF for PDLSC differentiation toward fibroblasts. A mechanochemical coupling effect of MGF mediated the enhancement of mechanical effect, which was modulated by Fyn‐FAK kinases signaling and subsequent MAPK pathway. Finally, enhanced PDL regeneration under the mechanochemical coupling of MGF and occlusal force was verified in vivo. There exists an additive mechanical effect of MGF mediated by Fyn‐FAK crosstalk and subsequent ERK1/2 and p38 phosphorylation, which could be developed as an MGF‐centered adjuvant treatment to optimize PDL remodeling, especially for patients with weakened bite force or destroyed periodontium. [ABSTRACT FROM AUTHOR]

In this work, unique Co3O4/N‐doped reduced graphene oxide (Co3O4/N‐rGO) composites as favorable sulfur immobilizers and promoters for lithium–sulfur (Li–S) batteries are developed. The prepared Co3O4 nanopolyhedrons (Co3O4‐NP) and Co3O4 nanocubes mainly expose (112) and (001) surfaces, respectively, with different atomic configurations of Co2+/Co3+ sites. Experiments and theoretical calculations confirm that the octahedral coordination Co3+ (Co3+Oh) sites with different oxidation states from tetrahedral coordination Co2+ sites optimize the adsorption and catalytic conversion of lithium polysulfides. Specially, the Co3O4‐NP crystals loaded on N‐rGO expose (112) planes with ample Co3+Oh active sites, exhibiting stronger adsorbability and superior catalytic activity for polysulfides, thus inhibiting the shuttle effect. Therefore, the S@Co3O4‐NP/N‐rGO cathodes deliver excellent electrochemical properties, for example, stable cyclability at 1 C with a low capacity decay rate of 0.058% over 500 cycles, superb rate capability up to 3 C, and high areal capacity of 4.1 mAh cm−2. This catalyst's design incorporating crystal surface engineering and oxidation state regulation strategies also provides new approaches for addressing the complicated issues of Li–S batteries. [ABSTRACT FROM AUTHOR]

Tumor angiogenesis is a complex process that is unamenable to intravital whole‐process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging‐optical coherence tomography angiography (OCTA)‐laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo‐chemotherapy of tumor by monitoring blood oxygen saturation (SaO2) and hemoglobin content (HbT), but also capable of long‐term microscopic investigating the microvessel morphology (microvascular density) and hemodynamics changes (relative blood flow) before and after the nanotherapeutics in vivo. Moreover, to realize the tumor thermo‐chemotherapy treatment based on this novel multimodal imaging strategy, a 2D 5‐fluorouracil silicon nanosheets (5‐Fu‐Si NSs) therapeutic agent is designed. Furthermore, 2D high‐resolution tumor microvascular images in different stage display that tendency of the thermo‐chemotherapy effect is closely associated with tumor angiogenesis. Taken together, the investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor. More importantly, this technique will be beneficial to evaluate the tumor microvascular response to nanotherapeutics at microscale. [ABSTRACT FROM AUTHOR]

Tumor angiogenesis is a complex process that is unamenable to intravital whole‐process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging‐optical coherence tomography angiography (OCTA)‐laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo‐chemotherapy of tumor by monitoring blood oxygen saturation (SaO2) and hemoglobin content (HbT), but also capable of long‐term microscopic investigating the microvessel morphology (microvascular density) and hemodynamics changes (relative blood flow) before and after the nanotherapeutics in vivo. Moreover, to realize the tumor thermo‐chemotherapy treatment based on this novel multimodal imaging strategy, a 2D 5‐fluorouracil silicon nanosheets (5‐Fu‐Si NSs) therapeutic agent is designed. Furthermore, 2D high‐resolution tumor microvascular images in different stage display that tendency of the thermo‐chemotherapy effect is closely associated with tumor angiogenesis. Taken together, the investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor. More importantly, this technique will be beneficial to evaluate the tumor microvascular response to nanotherapeutics at microscale. [ABSTRACT FROM AUTHOR]

Aims: MITF, TFE3, TFEB and TFEC belong to the same microphthalmia‐associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1–TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC–MITF gene fusion by RNA sequencing. Methods and results: Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in‐situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription–polymerase chain reaction confirmed the presence of a PRCC–MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break‐apart probes and PRCC–MITF fusion probes to detect the MITF gene rearrangement. Conclusions: This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate potential molecular mechanisms associated with loss of BRM expression in poorly differentiated clear cell renal cell carcinoma (cc RCC). Methods and results Nineteen previously selected BRM-negative RCC tissues were examined by DNA sequencing, fluorescence in-situ hybridization ( FISH) and methylation-specific polymerase chain reaction ( PCR) of the BRM gene. BRM mutation was identified in 78.9% (15 of 19) cases, chromosome 9 monosomy or BRM deletion in 43.8% (seven of 16) and BRM promoter region cytosine-phosphate-guanine (CpG) methylation in 42.8% (six of 14). These results indicated that 89.5% (17 of 19) of the cases harboured at least one type of BRM genetic alteration, with two or more types of alteration in 47.4% (nine of 19). Such alterations were found rarely in adjacent non-neoplastic tissues and low-grade areas of composite tumours. Conclusions BRM gene mutation, chromosome 9 monosomy or BRM deletion and CpG methylation contribute collectively to the loss of BRM expression in cc RCC. This work focusing on composite tumours indicated that BRM abnormality occurred during tumour progression. [ABSTRACT FROM AUTHOR]

The integration effects on flatness control during hot rolling process is studied for meeting the requirement of schedule-free rolling (SFR) campaigns of non-oriented electrical steel strips with identical width. A 3D finite element model for elastic deformation of rolls is built by ANSYS. The integration effects of lubrication, asymmetry self-compensating work rolls (ASR), and varying contact back-up roll (VCR) contours on flatness control are comparatively analyzed. An improved strip profile, flatness, and rolling stability are achieved by combining these technologies. The total rolling coil number is increased from 70 to 100 within a rolling campaign. The lateral stiffness of roll gap is increased by 10.3 and 12.75% in the early and later rolling stage, respectively. [ABSTRACT FROM AUTHOR]

Recently, an increasing number of TFE3 rearrangement-associated tumours have been reported, such as TFE3 rearrangement-associated perivascular epithelioid cell tumours ( PEComas), melanotic Xp11 translocation renal cancers and melanotic Xp11 neoplasms. We have suggested that these tumours belong to a single clinicopathological spectrum. 'Xp11 neoplasm with melanocytic differentiation' or 'melanotic Xp11 neoplasm' have been proposed to designate this unique neoplasm. Herein, we describe the first case of an Xp11 neoplasm with melanocytic differentiation to be described in the prostate, bearing the novel NONO- TFE3 gene fusion. This study both adds to the spectrum regarding melanotic Xp11 neoplasms and expands its gene fusion spectrum. Moreover, we discuss the relationship of these rare tumours to neoplasms such as conventional PEComas, alveolar soft part sarcomas, malignant melanomas, clear cell sarcomas and Xp11 translocation renal cancers. [ABSTRACT FROM AUTHOR]

A key issue for perovskite solar cells is the stability of perovskite materials due to moisture effects under ambient conditions, although their efficiency is improved constantly. Herein, an improved CH3NH3PbI3− xCl x perovskite quality is demonstrated with good crystallization and stability by using water as an additive during crystal perovskite growth. Incorporating suitable water additives in N, N-dimethylformamide (DMF) leads to controllable growth of perovskites due to the lower boiling point and the higher vapor pressure of water compared with DMF. In addition, CH3NH3PbI3− xCl x · nH2O hydrated perovskites, which can be resistant to the corrosion by water molecules to some extent, are assumed to be generated during the annealing process. Accordingly, water additive based perovskite solar cells present a high power conversion efficiency of 16.06% and improved cell stability under ambient conditions compared with the references. The findings in this work provide a route to control the growth of crystal perovskites and a clue to improve the stability of organic-inorganic halide perovskites. [ABSTRACT FROM AUTHOR]

Aims Malignant rhabdoid tumours ( MRTs) are highly aggressive malignancies of early infancy characterized by inactivation of SMARCB1, a core member of the SWI/ SNF chromatin-remodelling complex. The aim of this study was to explore the status of multiple key subunits of the SWI/ SNF complex in MRTs. Methods and results We screened the key subunits of the SWI/ SNF complex, including SMARCB1, SMARCA2, PBRM1, SMARCA4, and ARID1A, in four MRTs by immunohistochemistry, sequencing, and fluorescence in-situ hybridization ( FISH). Complete loss of SMARCB1, SMARCA2 and PBRM1 expression and corresponding mutations in the same genes were observed in all cases. The mutations included seven missense, three same-sense, four frameshift and two truncating mutations. FISH revealed heterozygous deletion of SMARCB1 in one case, and monoploidy of chromosome 22, which harbours SMARCB1, in another case. Furthermore, trisomy of chromosome 9, which harbours SMARCA2, was observed in two cases. Abnormality of PBRM1 was not found in any case. Conclusions We report, for the first time, co-inactivation and frequent mutations of SMARCB1, SMARCA2 and PBRM1 in MRTs. Multiple subunit abnormalities of the SWI/ SNF complex potentially act together to contribute to the tumorigenesis of MRTs, which provides unique insights into this disease. [ABSTRACT FROM AUTHOR]

According to the requirement and condition of schedule-free rolling (SFR) for non-oriented electrical steel production with a large number of the same width strip rolling campaigns, asymmetry self-compensating work rolls (ASR) bending force mathematical model for different rolling schedules is established. Based on ANSYS software package, a 3D finite element model of roll stacks is established on the consideration of roll wear and thermal contour of work rolls. The effects of the bending force, the strip width, the rolling force, the diameters of backup and work rolls, the work roll shifting stroke on the loaded roll gap crown in rolling process are quantitatively analyzed. The developed ASR bending force mathematical model for different conditions is proved to be reasonable and has been applied to the 1700 hot strip mills. [ABSTRACT FROM AUTHOR]

Gastric cancer is the second most prominent cause of cancer mortality in the world. This study was designed to identify the possible use of si- RNA-mediated PDLIM5 gene silencing as a therapeutic tool for gastric cancer. Expression levels of PDLIM5 were detected in several gastric cancer cell lines using Western blot and qRT- PCR. We found PDLIM5 is highly expressed in all cultured gastric cancer cell lines. Small interfering RNA (si- RNA) was then employed to knock down PDLIM5 expression in MGC80-3 gastric cancer cells. Knockdown of PDLIM5 significantly inhibited cell proliferation and colony formation. Moreover, the absence of PDLIM5 in MGC80-3 cells led to S phase cell cycle arrest and apoptosis. This study highlights the critical role of PDLIM5 in gastric cancer cell growth and suggests that si- RNA-mediated silencing of PDLIM5 might serve as a potential therapeutic approach for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

B Thermo-Chemotherapy b A promising biocompatible nanotheranostics agent based on chemotherapeutic drug 5-fluorouracil and 2D silicon nanosheets is developed for synergistic thermo-chemotherapy strategy. The tumor tissue functional parameters, including SaO SB 2 sb , HbT, micro microvascular morphology, and hemodynamics, are dynamically monitored by multimodal PA/OCTA/LS imaging strategy to accurately evaluate overall therapeutic effects. Intravital Whole-Process Monitoring Thermo-Chemotherapy Via 2D Silicon Nanoplatform: A Macro Guidance and Long-Term Microscopic Precise Imaging Strategy (Adv. Sci. 16/2021). [Extracted from the article]

Intravital Whole-Process Monitoring Thermo-Chemotherapy Via 2D Silicon Nanoplatform: A Macro Guidance and Long-Term Microscopic Precise Imaging Strategy (Adv. Sci. 16/2021) B Thermo-Chemotherapy b A promising biocompatible nanotheranostics agent based on chemotherapeutic drug 5-fluorouracil and 2D silicon nanosheets is developed for synergistic thermo-chemotherapy strategy. The tumor tissue functional parameters, including SaO SB 2 sb , HbT, micro microvascular morphology, and hemodynamics, are dynamically monitored by multimodal PA/OCTA/LS imaging strategy to accurately evaluate overall therapeutic effects. [Extracted from the article]

Necroptosis is crucially involved in severe cardiac pathological conditions. However, whether necroptosis contributes to age‐related intolerance to ischemia/reperfusion (I/R) injury remains elusive. In addition, metformin as a potential anti‐aging related injury drug, how it interacts with myocardial necroptosis is not yet clear. Male C57BL/6 mice at 3–4‐ (young) and 22–24 months of age (aged) and RIPK3‐deficient (Ripk3−/−) mice were used to investigate aging‐related I/R injury in vivo. Metformin (125 μg/kg, i.p.), necrostatin‐1 (3.5 mg/kg), and adenovirus vector encoding p62‐shRNAs (Ad‐sh‐p62) were used to treat aging mice. I/R‐induced myocardial necroptosis was exaggerated in aged mice, which correlated with autophagy defects characterized by p62 accumulation in aged hearts or aged human myocardium. Functionally, blocking autophagic flux promoted H/R‐evoked cardiomyocyte necroptosis in vitro. We further revealed that p62 forms a complex with RIP1‐RIP3 (necrosome) and promotes the binding of RIP1 and RIP3. In mice, necrostatin‐1 treatment (a RIP1 inhibitor), RIP3 deficiency, and cardiac p62 knockdown in vivo demonstrated that p62‐RIP1‐RIP3‐dependent myocardial necroptosis contributes to aging‐related myocardial vulnerability to I/R injury. Notably, metformin treatment disrupted p62‐RIP1‐RIP3 complexes and effectively repressed I/R‐induced necroptosis in aged hearts, ultimately reducing mortality in this model. These findings highlight previously unknown mechanisms of aging‐related myocardial ischemic vulnerability: p62‐necrosome‐dependent necroptosis. Metformin acts as a cardioprotective agent that inhibits this unfavorable chain mechanism of aging‐related I/R susceptibility. [ABSTRACT FROM AUTHOR]