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The frequency and intensity of extreme weather events, including rapid temperature fluctuations, are increasing because of climate change. Long-term fertilization practices have been observed to alter microbial physiology and community structure, thereby affecting soil carbon sequestration. However, the effects of warming on the carbon sequestration potential of soil microbes adapted to long-term fertilization remain poorly understood. In this study, we utilized 18O isotope labeling to assess microbial carbon use efficiency (CUE) and employed stable isotope probing (SIP) with 18O-H2O to identify growing taxa in response to temperature changes (5–35 °C). Organic amendment with manure or straw residue significantly increased microbial CUE by 86–181 % compared to unfertilized soils. The microorganisms inhabiting organic amended soils displayed greater resistance of microbial CUE to high temperatures (25–35 °C) compared to those inhabiting soils fertilized only with minerals. Microbial growth patterns determined by the classification of taxa into incorporators or non-incorporators based on 18O incorporation into DNA exhibited limited phylogenetic conservation in response to temperature changes. Microbial clusters were identified by grouping taxa with similar growth patterns across different temperatures. Organic amendments enriched microbial clusters associated with increased CUE, whereas clusters in unfertilized or mineral-only fertilized soils were linked to decreased CUE. Specifically, shifts in the composition of growing bacteria were correlated with enhanced microbial CUE, whereas modifications in the composition of growing fungi were associated with diminished CUE. Notably, the responses of microbial CUE to temperature fluctuations were primarily driven by changes in the bacterial composition. Overall, our findings demonstrate that organic amendments enhance soil microbial CUE and promote the enrichment of specific microbial clusters that are better equipped to cope with temperature changes. This study establishes a theoretical foundation for manipulating soil microbes to enhance carbon sequestration under global climate scenarios.

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo, and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field.

Objective: To explore the kidney yang deficiency pattern (KYDP) in a chronic kidney disease (CKD) rat model and the mechanisms underlying the effects of Zhenwu decoction (ZWD) by conducting transcriptomic and metabolomic analyses. Methods: Adriamycin (ADR) combined with hydrocortisone (HC) was used to induce CKD with KYDP in rats. ADR was injected into the tail vein twice. HC was injected intramuscularly for 8 weeks. ZWD was administered by gavage for 8 weeks. The general condition was observed, 24-h urine protein was detected, serum corticosterone, triiodothyronine, thyroxine, TSH, testosterone, cAMP, and cGMP levels were determined, and pathological analysis was conducted. Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes (DEGs), differentially expressed metabolites (DEMs), and differentially expressed pathways (DEPs). The core DEMs and DEGs were input to Metaboanalyst 5.0 to identify the pathways affected by ZWD. Results: In the HC group, KYDP symptoms were observed. Compared with control group, the levels of 24-h urine protein, TSH, and cGMP significantly increased (all P

Objective: To explore the protective effect and potential mechanisms of danshen root (Salvia miltiorrhiza Bge., S. miltiorrhiza) and its extracts for the treatment of diabetic nephropathy (DN). Methods: Preclinical studies of S. miltiorrhiza and its extracts on DN were systematically searched in nine databases. The primary outcomes were blood glucose, kidney function, proteinuria, and renal histopathology. The secondary outcomes included the related mechanisms. The methodological quality of animal studies was assessed based on the risk of bias tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) for animal studies. Meta-analysis was performed using R software (version 4.1.2). Results: Twenty-nine animal experimental studies that met the eligibility criteria were included in this study. Compared to the control group, S. miltiorrhiza reduced the serum creatinine, blood urea nitrogen, 24-h urine protein, 24-h urine albumin, blood glucose, and kidney index (kidney weight/body weight), and alleviated renal pathological damage. In terms of the mechanism of action, compared to the control group, S. miltiorrhiza reduced the levels of transforming growth factor β1, collagen IV, malondialdehyde, tumor necrosis factor α, interleukin-6, and monocyte/macrophage (ED-1), and increased the levels of superoxide dismutase, glutathione peroxidase, nuclear factor E2–related factor 2, and heme oxygenase-1. Conclusion: The existing evidence shows that S. miltiorrhiza has beneficial effects on the animal model of DN, and its mechanism is mainly related to improving kidney fibrosis, oxidative stress, and inflammatory response.

The Türkiye-Syria earthquake doublet of 6 February 2023 (Mw 7.8 at 01:17 UTC and Mw 7.6 at 10:24 UTC) resulted in extensive damage and tens of thousands of casualties. We present the surface displacements of the two earthquakes from synthetic aperture radar (SAR) offset tracking measurements. We extracted the geometric parameters of the rupture faults from the surface displacements and early aftershock distribution, based on which we inverted the coseismic slip distributions. We then calculated Coulomb stress to investigate the triggering relationship between the earthquakes and stress transfer to neighbouring faults and regions. The coseismic ruptures of the earthquake doublet were predominantly left-lateral strike-slip motions distributed between 0 and 15 km depth. The maximum fault slip reached > 8 m (Mw 7.8) and almost 10 m (Mw 7.6). The coseismic deformation and fault slip motion are consistent with the overall westward extrusion of the Anatolian Plate relative to the Eurasian and Arabian plates. The Mw 7.8 earthquake increased Coulomb failure stress at the hypocenter of the Mw 7.6 earthquake, implying that the Mw 7.8 event had a strong positive causative effect. Moreover, coseismic stress perturbations revealed a positive Coulomb stress effect on the middle Puturge Fault, northern Dead Sea Fault Zone (DSFZ), Yesemek Fault, Antakya Fault, and Turkoglu Fault, indicating an increasing seismic hazard in these regions.

Abstract Bacteria are essential regulators of soil biogeochemical cycles. While several studies of bacterial elevational patterns have been performed in recent years, the drivers of these patterns remain incompletely understood. To clarify bacterial distribution patterns and diversity across narrow- and broad-scale elevational gradients, we collected soil samples from 22 sites in the grasslands of Mt. Tianshan in China along three elevational transects and the overall elevation transect: (1) 6 sites at elevations of 1047–1587 m, (2) 8 sites at 876–3070 m, and (3) 8 sites at 1602–2110 m. The bacterial community diversity across the overall elevation transects exhibited a hump-like pattern, whereas consistent patterns were not observed in the separate elevational transects. The bacterial community composition at the phylum level differed across the transects and elevation sites. The Actinobacteria was the most abundant phylum overall (41.76%) but showed clear variations in the different transects. Furthermore, heatmap analyses revealed that both pH and mean annual temperature (MAT) were significantly (P

Located in the East Kunlun Orogen, China, the Xiarihamu magmatic nickel–cobalt sulfide deposit is the country’s second largest deposit of this type. It was formed in special early Paleozoic with low copper grade (0.14 wt%) compared with other deposits of the same type. The mineralogy of nickel and cobalt minerals, which are direct carriers of these elements, can clearly reflect their behavior in the process of mineralization; however, such information for this deposit remains unreported. In the present study, we use an electron microscope and electron probe microanalyzer to delineate and analyze many nickel and cobalt minerals such as maucherite, nickeline, cobaltite, violarite, gersdorffite, parkerite, and arsenohauchecornite in various rocks and ores. With the increase in crustal material contamination, it can reach arsenide saturation locally in sulfide melt, then a separate Ni-rich arsenide (bismuth) melt exsolves somewhere. This melt will crystallize into nickeline, parkerite, arsenohauchecornite, and maucherite first. Second, most of nickel and cobalt tend to enter cobaltite and pentlandite phases, rather than existing in chalcopyrite and pyrrhotite phases as isomorphism during sufficient fractional crystallization of sulfide melt, which gathered nickel and cobalt elements widely. Also, more than one magma might result in the superposition of ore-forming elements. Later, the ore-forming elements redistribute limitedly through a hydrothermal process. The metallogenic mechanism model of nickel and cobalt established in the present study not only explains the process of nickel–cobalt mineralization in Xiarihamu but also can be applied to similar deposits and has a wide universal replicability.

As the northern boundary of the Tibetan Plateau, the long Altyn Tagh fault (ATF) controls the regional tectonic environment, and the study of its long-term fault slip rate is key to understanding the tectonic evolution and deformation of the northern Tibetan Plateau. In this paper, we measure the fault slip rate of the western segment of the ATF using InSAR observations between 2015 to 2020. The Multi-Temporal Interferometric InSAR analysis is applied to obtain the two-dimensional fault-parallel and vertical displacement fields. The spatially dense InSAR observations clearly illustrate the asymmetrical pattern of displacement fields across the fault. Constrained by our InSAR observations, the fault slip rate and locking depth of the western segment of the ATF are inverted using four different models in a Bayesian framework. The two-layer viscoelastic model incorporating lateral heterogeneity of rheology in the lower crust indicates that the fault slip rate of the western ATF is estimated to be 9.8 ± 1.1 mm/yr (at 83.8°E across the ATF) and 8.6 ± 1.1 mm/yr (at 85.1°E), respectively, and the locking depth is 15.8 ± 4.3 km and 14.8 ± 4.9 km. Our new estimates generally agree with the previous estimates of fault slip rate constrained by GPS observations. We conclude that the contrast between the thickness of the elastic layer and the shear modulus of the Tibetan plateau and the Tarim basin jointly contribute to the asymmetric interseismic strain accumulation on the ATF.

Financing by patent pledge is an important way for small- and medium-sized pharmaceutical enterprises to address financing problems. In this study, eight indexes are analyzed considering both the pledge patent value and pledger credit value. And a prediction model for the patent pledge financing amount for pharmaceutical enterprises is constructed for the first time using the analytic hierarchy process and the fuzzy comprehensive evaluation method. Three levels of financing amount are concluded through the prediction model and prediction results corresponding with the financing amount are displayed. This model was designed to help small- and medium-sized pharmaceutical enterprises get access to financing through patent pledge to relieve their financial stress. At the same time, it provides guides for pledgees and policymakers to improve the efficiency and quality of patent pledge. This work is reliable and valid in that it constructs this prediction model based on systematical data from official data sources.

The 17q23 amplicon containing the WIP1 oncogene is frequently amplified in HER2+ breast cancer. Here they find MIR21 to be present in WIP1-containing amplicons, and report nanoparticle based co-delivery of WIP1 and miR-21 inhibitors to be effective in trastuzumab-resistant HER2+ breast cancer.

Heterozygous loss of chromosome 17p is a common genomic event in castration-resistant prostate cancers (CRPC). Here, the authors use CRISPR-based screen to identify RBX1 as a target gene for CRPC with 17p loss and targeting RBX1 sensitizes CRPC to the treatment of α-amanitin antibody conjugates.

Cancer cells need to reprogramme their metabolism to allow rapid cell proliferation. Here, the authors show that USP13is amplified in ovarian cancer and its protein product, a deubiquitinase, drives tumour progression by rewiring the metabolism of cancer cells by stabilising two critical metabolic enzymes.

Posttranscriptional maturation is a critical step in microRNA (miRNA) biogenesis that determines mature miRNA levels. In addition to core components (Drosha and DGCR8 [DiGeorge syndrome critical region gene 8]) in the microprocessor, regulatory RNA-binding proteins may confer the specificity for recruiting and processing of individual primary miRNAs (pri-miRNAs). Here, we identify DDX1 as a regulatory protein that promotes the expression of a subset of miRNAs, including five members in the microRNA-200 (miR-200) family and four miRNAs in an eight-miRNA signature of a mesenchymal ovarian cancer subtype. A majority of DDX1-dependent miRNAs are induced after DNA damage. This induction is facilitated by the ataxia telangiectasia mutated (ATM)-mediated phosphorylation of DDX1. Inhibiting DDX1 promotes ovarian tumor growth and metastasis in a syngeneic mouse model. Analysis of The Cancer Genome Atlas (TCGA) reveals that low DDX1 levels are associated with poor clinical outcome in patients with serous ovarian cancer. These findings suggest that DDX1 is a key modulator in miRNA maturation and ovarian tumor suppression.

Expression of microRNAs (miRNAs) involves transcription of miRNA genes and maturation of the primary transcripts. Recent studies have shown that posttranscriptional processing of primary and precursor miRNAs is induced after DNA damage through regulatory RNA-binding proteins in the Drosha and Dicer complexes, such as DDX5 and KSRP. However, little is known about the regulation of nuclear export of pre-miRNAs in the DNA-damage response, a critical step in miRNA maturation. Here, we show that nuclear export of pre-miRNAs is accelerated after DNA damage in an ATM-dependent manner. The ATM-activated AKT kinase phosphorylates Nup153, a key component of the nucleopore, leading to enhanced interaction between Nup153 and Exportin-5 (XPO5) and increased nuclear export of pre-miRNAs. These findings define an important role of DNA-damage signaling in miRNA transport and maturation.

The relationship between species richness (SR) and aboveground net primary productivity (ANPP) is still a central and debated issue in community ecology. Previous studies have often emphasized the relationship of alpha diversity (number of species identity) to the mean ANPP with respect to the SR-ANPP relationship while neglecting the contribution of beta diversity (dissimilarity in species composition) to the mean ANPP and to the stability of ANPP (coefficient of ANPP: CV of ANPP). In this study, we used alpha and beta diversity, mean ANPP and the CV of ANPP collected from 159 sites and belonging to three vegetation types in the Xinjiang temperate grassland to first examine their trends along climatic factors and among different vegetation types and then test the relationship among alpha (beta) diversity and mean ANPP and the CV of ANPP. Our results showed that in the Xinjiang temperate grasslands, alpha diversity was positively and linearly correlated with MAP but unimodally correlated with MAT. Meanwhile, beta diversity was unimodally correlated with MAP but linearly correlated with MAT. Relative to desert steppe, meadow steppe and typical steppe had the highest alpha and beta diversity, respectively. Except for ANPP exhibiting a quadratic relationship with MAP, no significant relationship was found among ANPP, the CV of ANPP and climatic factors. ANPP and the CV of ANPP also exhibited no apparent patterns in variation among different vegetation types. Our results further showed that mean ANPP was closely associated with alpha diversity. Both linear and unimodal relationships were detected between alpha diversity and mean ANPP, but their particular form was texture-dependent. Meanwhile, the CV of ANPP was positively correlated with beta diversity. Our results indicated that in addition to incorporating alpha diversity and mean ANPP, incorporating beta diversity and the CV of ANPP could expand our understanding of the SR-ANPP relationship.

Investigating relationships between temporally- and spatially-related continental earthquakes is important for a better understanding of the crustal deformation, the mechanism of earthquake nucleation and occurrence, and the triggering effect between earthquakes. Here we utilize Global Positioning System (GPS) velocities before and after the 2008 Mw 7.9 Wenchuan earthquake to invert the fault coupling of the Longmenshan Fault (LMSF) and investigate the impact of the 2008 Mw 7.9 Wenchuan earthquake on the 2013 Mw 6.6 Lushan earthquake. The results indicate that, before the 2008 Mw 7.9 Wenchuan earthquake, fault segments were strongly coupled and locked at a depth of ~18 km along the central and northern LMSF. The seismic gap between the two earthquake rupture zones was only locked at a depth < 5 km. The southern LMSF was coupled at a depth of ~10 km. However, regions around the hypocenter of the 2013 Mw 6.6 Lushan earthquake were not coupled, with an average coupling coefficient ~0.3. After the 2008 Mw 7.9 Wenchuan earthquake, the central and northern LMSF, including part of the seismic gap, were decoupled, with an average coupling coefficient smaller than 0.2. The southern LMSF, however, was coupled to ~20 km depth. Regions around the hypocenter of the 2013 Mw 6.6 Lushan earthquake were also coupled. Moreover, by interpreting changes of the GPS velocities before and after the 2008 Mw 7.9 Wenchuan earthquake, we find that the upper crust of the eastern Tibet (i.e., the Bayan Har block), which was driven by the postseismic relaxation of the 2008 Mw 7.9 Wenchuan earthquake, thrust at an accelerating pace to the Sichuan block and result in enhanced compression and shear stress on the LMSF. Consequently, downdip coupling of the fault, together with the rapid accumulation of the elastic strain, lead to the occurrence of the 2013 Mw 6.6 Lushan earthquake. Finally, the quantity analysis on the seismic moment accumulated and released along the southern LMSF show that the 2013 Mw 6.6 Lushan earthquake should be defined as a “delayed” aftershock of the 2008 Mw 7.9 Wenchuan earthquake. The seismic risk is low along the seismic gap, but high on the unruptured southwesternmost area of the 2013 Mw 6.6 Lushan earthquake.