AbstractObjectiveTo study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for ...coronavirus disease 2019 (covid-2019).DesignRetrospective case series.SettingSeven hospitals in Zhejiang province, China.Participants62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020.Main outcome measuresClinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification.ResultsOf the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days.ConclusionAs of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.
Porphyry copper deposits account for more than 80% of the world’s total Cu resources. However, the formation mechanism and controlling factors of porphyry copper deposits remain obscure. Previous ...studies have revealed that porphyry copper deposits are usually associated with oxidized, calc-alkalic, adakitic shallow intrusive rocks. Here we show that hematite–magnetite intergrowths are commonly found in porphyry copper deposits, suggesting high and fluctuating oxygen fugacity (fO2). Oxidation promotes the destruction of sulfides in the magma source, and thereby increases initial chalcophile element concentrations. Sulfide remains undersaturated during the evolution of oxidized sulfur-enriched magmas where sulfate is the dominant sulfur species, leading to high chalcophile element concentrations in evolved magmas. The final porphyry copper mineralization is controlled by sulfate reduction, which starts with magnetite crystallization, accompanied by decreasing pH and correspondingly increasing fO2. Hematite forms once sulfate reduction lowers the pH sufficiently and the fO2 reaches the hematite–magnetite oxygen fugacity buffer, which in turn increases the pH for a given fO2. The oxidation of ferrous iron during the crystallization of magnetite and hematite is the causal process of sulfate reduction and consequent mineralization. Therefore, the initial pH and fO2 ranges of porphyries favorable for porphyry copper mineralization are defined by the hematite–magnetite oxygen fugacity buffer and SO42−–HS−–S3− reaction lines. Adakitic rocks have higher initial contents of copper, sulfur and iron than normal arc rocks, and thus are the best candidates for porphyry copper deposits. These provide a plausible explanation for the formation of copper porphyry deposits. The hematite–magnetite intergrowth marks the upper limits of fO2 favorable for the mineralization, and thus may be a powerful tool for future prospecting of large porphyry copper deposits.
Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in ...the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects.
To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP).
Exercise therapy appears to be effective at decreasing pain and improving function ...for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP.
Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies.
From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain mean difference (-1.29); 95% confidence interval (-2.47, -0.11); P = 0.003 and disability mean difference (-7.14); 95% confidence interval (-11.64, -2.65); P = 0.002 at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months mean difference (-0.50); 95% confidence interval (-1.36, 0.36); P = 0.26 and 12 months mean difference (-0.32); 95% confidence interval (-0.87, 0.23); P = 0.25.
Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise.
http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717.
Summary
Autophagy is a conserved degradation system in eukaryotic cells that includes non‐selective and selective processes. Selective autophagy functions as a selective degradation mechanism for ...specific substrates in which autophagy‐related protein 11 (ATG11) acts as an essential scaffold protein. In B. bassiana, there is a unique ATG11 family protein, which is designated as BbATG11. Disruption of BbATG11 resulted in significantly reduced conidial germination under starvation stress. The mutant ΔBbATG11 displayed enhanced sensitivity to oxidative stress and impaired asexual reproduction. The conidial yield was reduced by approximately 75%, and this defective phenotype could be repressed by increasing exogenous nutrients. The virulence of the ΔBbATG11 mutant strain was significantly impaired as indicated in topical and intra‐hemocoel injection bioassays, with a greater reduction in topical infection. Notably, BbATG11 was involved in pexophagy and mitophagy, but these two autophagic processes appeared in different fungal physiological aspects. Both pexophagy and mitophagy were associated with nutrient shift, starvation stress and growth in the host hemocoel, but only pexophagy appeared in both oxidation‐stressed cells and aerial mycelia. This study highlights that BbATG11 mediates pexophagy and mitophagy in B. bassiana and links selective autophagy to the fungal stress response, conidiation and virulence.
Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This ...disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses.
A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted.
All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant.
This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.
► The Shennongjia suite is typical of a mid-Grenvillian arc volcanic sequence ► Microcontinents comprise the Yangtze Block before collision with the Cathaysia ► The Yangtze Block underwent a lateral ...continental growth during the Grenvillian ► It infers a western Yangtze-South Australia connection during Rodinia assembly.
The Grenvillian (1.3–1.0
Ga) orogenic and subduction related events have been regarded as a critical linkage in Rodinia reconstruction. Here we report the first recognized late Mesoproterozoic arc-volcanic sequence in South China. The volcanic sequence is well-exposed in the Shennongjia region, along the northern central margin of the Yangtze Block, and has previously been mapped as a volcanic sequence interbedded with early Mesoproterozoic strata, but reliable dating data have been lacking.
The volcanic sequence comprises alkali-, calc-alkaline basalts and tholeiitic andesitic rocks, and is dated at 1103
±
8
Ma by the U–Pb zircon method. The alkali basalts have high TiO
2 (2.62–4.48
wt.%) and relatively low Mg# (42–55), and display OIB-like incompatible elemental patterns. They have initial Sr isotopic ratios of 0.7021–0.7056 and
ɛ
Nd(
t) values of +2.4 to +4.0. By contrast, the calc-alkaline basalts have high Mg# (57–68), Cr (67.1–211
ppm) and Ni (62.8–121
ppm), and exhibit a pronounced depletion in high field strength elements (Nb, Ta, P and Ti) and positive Pb anomalies. Compared to the alkali basalts, they possess higher initial Sr isotopic ratios of 0.7086–0.7120 and large negative
ɛ
Nd(
t) values of −15.3 to −14.2. The andesitic rocks are characterized by negative Eu anomalies (Eu/Eu
*
=
0.62–0.65) and depleted Nb, Ta, P and Ti anomalies along with small negative
ɛ
Nd values (−2.7 to −2.1) and low Sr isotopic ratios (0.7028–0.7042).
It is suggested that the alkali basalts were derived from a depleted asthenospheric mantle source, the calc-alkaline basalts from previously metasomatised subcontinental lithospheric mantle rocks, whereas the andesitic rocks were derived from mafic lower crustal anatexis induced by basaltic underplating and/or asthenospheric ascent. The Shennongjia volcanic sequence is thus proposed to have developed within an island-arc setting. Integrating our new data with documented igneous and metamorphic events during the end Mesoproterozoic to early Neoproterozoic, the northwestern and western segments of the Yangtze Block likely comprised a collage of microcontinents during the Grenvillian period and underwent westward lateral continental growth by subduction accretion and microcontinent growth by subduction-related collision. Given the documented ∼1.6
Ga peak population of detrital zircon spectra for the lower Shennongjia strata, ∼1.6
Ga significant juvenile mantle input in the Shennongjia area and ∼1.1
Ga Grenvillian metamorphic record in the westernmost Yangtze segment, we suggest a western Yangtze-South Australia connection during Rodinia assembly of the Grenvillian period. It thus provides a new insight into the position of the South China Craton in the supercontinent.
Summary
The gelsolin superfamily includes seven protein members: gelsolin, villin, adseverin, CapG, advillin, supervillin and flightless I. The gelsolin proteins are actin‐binding proteins that ...contain three or six gelsolin‐like domains, and they play important roles in remodelling actin dynamics and cellular processes in eukaryotes. The entomopathogenic fungus Beauveria bassiana expresses a unique CapG protein (BbGEL1) that contains three gelsolin‐like domains. BbGEL1p is associated with actin during mycelial growth and plays an important role in fungal morphological transitions under both aerobic and submerged conditions. The ΔBbGEL1 mutant displays abnormal spore‐producing structures that reduce the conidial and blastospore yields by approximately 70% and 90% respectively. The virulence of the ΔBbGEL1 mutant is notably reduced as indicated by topical and intrahemocoel injection assays. Two comparative proteomics analyses indicated that BbGEL1 has significantly different roles in the development of conidia and blastospores, and the results revealed the potential targets of BbGEL1 in the corresponding developmental processes. Additionally, as an overlapping downstream protein of BbGEL1, the hydrophobin‐like protein gene BbHyd3 is required for conidiation but has a negative role in blastospore formation. Our findings indicate that in addition to its function as an actin‐interacting protein, BbGEL1 contributes to fungal morphological transitions via broad genetic pathways.
Significant debate has been noted in the α-ω and ω-β phase transformations of zirconium. The initial pressure of the α-to-ω transformation at room temperature has been reported to vary from 0.25 to ...7.0 GPa, while the hydrostatic transformation is believed to occur at approximately 2.2 GPa. Shear stress is commonly considered as a key factor leading to the discrepancy. However, the principal mechanisms previously proposed concluded that the phase transformation pressure would be decreased in the presence of shear stress. The experimental results of the α-ω transformation in zirconium are contrary to this conclusion. In the ω-β phase diagram of zirconium, the dT/dP along the phase boundary near the α-ω-β triple-point was reported to be either positive or negative, but no theoretical explanation, especially a quantitative one, has been proposed. This article aimed to quantitatively investigate and explain the controversies reported in the α-ω and ω-β phase transformations of zirconium by applying a new nonhydrostatic thermodynamic formalism for solid medium, which has recently been proposed and is capable of quantitatively estimating the impact of shear stress on phase transformations in solids.
Cholesterol gallstone disease is a prevalent condition that has a significant economic impact. However, the role of the bile microbiome in its development and the host's responses to it remain poorly ...understood.
In this study, we conducted a comprehensive analysis of microbial and human bile proteins in 40 individuals with either gallstone disease or gallbladder polyps. We employed a combined proteomic and metaproteomic approach, as well as meta-taxonomic analysis, functional pathway enrichment, and Western blot analyses.
Our metaproteomic analysis, utilizing the lowest common ancestor algorithm, identified 158 microbial taxa in the bile samples. We discovered microbial taxa that may contribute to gallstone formation, including β-glucuronidase-producing bacteria such as Streptococcus, Staphylococcus, and Clostridium, as well as those involved in biofilm formation like Helicobacter, Cyanobacteria, Pseudomonas,
, and Clostridium. Furthermore, we identified 2,749 human proteins and 87 microbial proteins with a protein false discovery rate (FDR) of 1% and at least 2 distinct peptides. Among these proteins, we found microbial proteins crucial to biofilm formation, such as QDR3, ompA, ndk, pstS, nanA, pfIB, and dnaK. Notably, QDR3 showed a gradual upregulation from chronic to acute cholesterol gallstone disease when compared to polyp samples. Additionally, we discovered other microbial proteins that enhance bacterial virulence and gallstone formation by counteracting host oxidative stress, including sodB, katG, rbr, htrA, and ahpC. We also identified microbial proteins like lepA, rtxA, pckA, tuf, and tpiA that are linked to bacterial virulence and potential gallstone formation, with lepA being upregulated in gallstone bile compared to polyp bile. Furthermore, our analysis of the host proteome in gallstone bile revealed enhanced inflammatory molecular profiles, including innate immune molecules against microbial infections. Gallstone bile exhibited overrepresented pathways related to blood coagulation, folate metabolism, and the IL-17 pathway. However, we observed suppressed metabolic activities, particularly catabolic metabolism and transport activities, in gallstone bile compared to polyp bile. Notably, acute cholelithiasis bile demonstrated significantly impaired metabolic activities compared to chronic cholelithiasis bile.
Our study provides a comprehensive metaproteomic analysis of bile samples related to gallstone disease, offering new insights into the microbiome-host interaction and gallstone formation mechanism.
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