Search

AbstractWith the increase of mining depth and mining intensity of the large inclined extra-thick coal seam (LIETCS), the number of rock bursts increases significantly. In this paper, based on a rock burst during upper roadway driving of the LIETCS, the distribution characteristics and fracture mechanism of microseismic (MS) events are analyzed using data statistics and seismic moment tensor inversion. By means of mechanical analysis and numerical simulation, this paper studies the static load distribution characteristics and dynamic load action effect of the LIETCS under upper slice mining condition. Based on the theory of dynamic and static combined load, the mechanism of rock bursts is proposed. The results show that the coal and rock mass of the LIETCS are mainly destroyed by shearing. The “shear-clamping” stress produced by the joint action of the roof and floor is the static load source. In upper slice mining, the shear stress and energy of the coal pillar behind the slice and the coal body below the coal pillar always remain high. Under the superposition of floor dynamic load, the regional stress environment changes, which induces rock bursts. This study provides a theoretical basis for rock burst prevention under similar conditions.

ABSTRACTIn China, the number of newly reported HIV infections in older people is increasing rapidly. However, clear information on the impact of older people on HIV transmission is limited. This study aims to reveal the local HIV transmission patterns, especially how older people affect virus transmission. Subtype analysis based on available pol sequences obtained from HIV patients revealed that CRF01_AE and CRF08_BC were predominant in patients aged

Background: Coronavirus disease 2019 (COVID-19) is a global outbreak disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cytomegalovirus (CMV) infection can occur in critical COVID-19 patients and is associated with adverse clinical outcomes. Objective: The aim of this study was to explore the clinical characteristics and outcome of CMV infection in critical COVID-19 patients. Design: This was a retrospective cohort study. Methods: From May to September 2021, SARS-CoV-2 reverse transcription polymerase chain reaction (RT–PCR)-confirmed COVID-19 patients with intensive care unit (ICU) admission were enrolled. CMV infection was confirmed by PCR. Baseline characteristics, critical illness data and clinical outcomes were recorded and analyzed. Results: Seventy-two RT–PCR-confirmed COVID-19 patients with ICU admission were included during the study period and 48 (66.7%) patients required mechanical ventilation (MV). Overall, in-hospital mortality was 19.4%. Twenty-one (29.2%) patients developed CMV infection. Patients with CMV infection had a higher likelihood of diabetes, higher lactate dehydrogenase and lactate levels, and higher proportions of MV, anticoagulant, and steroid use. Patients with CMV infection were associated with longer duration of SARS-CoV-2 shedding, longer ICU and hospital stay, and fewer ventilator-free days. The independent risk factor for development of CMV infection was a higher accumulative steroid dose. Conclusion: CMV infection adversely impacted the outcomes of critical COVID-19 patients, resulting in longer ICU stays, longer mechanical ventilation uses and prolonged shedding of SARS-CoV-2.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pandemic that has resulted in millions of deaths worldwide. Critically ill COVID-19 patients who require intubation and develop nosocomial pneumonia, commonly caused by gram-negative bacilli, have a higher mortality rate than those without nosocomial pneumonia. Objectives: The aim of this study is to compare the clinical characteristics and outcomes and associated risk factors of Alpha and Omicron SARS-CoV-2 variants in critically ill patients on mechanical ventilation (MV) with nosocomial pneumonia. Design: This is a retrospective single-center cohort study. Methods: This observational study was conducted at Taipei Veterans General Hospital, Taiwan from May 2021 to September 2022. Critically ill patients who had confirmed SARS-CoV-2 infection and intubated on a MV with bacterial pneumonia were enrolled. Demographic data, laboratory results, and treatment information were collected and analyzed. In addition, clinical outcomes among different SARS-CoV-2 variants were examined. Results: This study included 94 critically ill COVID-19 patients who required intubation and intensive care unit (ICU) admission. The Alpha group had a longer duration of SARS-CoV-2 viral shedding, MV days, and ICU stay, while the Omicron group had older age, more comorbidities, higher APACHE II scores, and higher in-hospital mortality (47.0% versus 25.0%, p = 0.047). However, independent risk factors for in-hospital mortality included malignancy, lower serum albumin levels, and lack of Remdesivir treatment, except for the SARS-CoV-2 variant. Conclusion: Our study discovered a higher in-hospital mortality rate in severe COVID-19 patients with MV and secondary pneumonia infected with the Omicron variant compared to the Alpha variant; however, real independent risk factors for in-hospital mortality are malignancy, lower serum albumin level, and lack of Remdesivir treatment.

Abstract Background Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction. Methods Sotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo. Results In the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo. Conclusions We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.

Abstract In this study, we present the growth of monolayer MoS2 (molybdenum disulfide) film. Mo (molybdenum) film was formed on a sapphire substrate through e-beam evaporation, and triangular MoS2 film was grown by direct sulfurization. First, the growth of MoS2 was observed under an optical microscope. The number of MoS2 layers was analyzed by Raman spectrum, atomic force microscope (AFM), and photoluminescence spectroscopy (PL) measurement. Different sapphire substrate regions have different growth conditions of MoS2. The growth of MoS2 is optimized by controlling the amount and location of precursors, adjusting the appropriate growing temperature and time, and establishing proper ventilation. Experimental results show the successful growth of a large-area single-layer MoS2 on a sapphire substrate through direct sulfurization under a suitable environment. The thickness of the MoS2 film determined by AFM measurement is about 0.73 nm. The peak difference between the Raman measurement shift of 386 and 405 cm−1 is 19.1 cm−1, and the peak of PL measurement is about 677 nm, which is converted into energy of 1.83 eV, which is the size of the direct energy gap of the MoS2 thin film. The results verify the distribution of the number of grown layers. Based on the observation of the optical microscope (OM) images, MoS2 continuously grows from a single layer of discretely distributed triangular single-crystal grains into a single-layer large-area MoS2 film. This work provides a reference for growing MoS2 in a large area. We expect to apply this structure to various heterojunctions, sensors, solar cells, and thin-film transistors.

ABSTRACTNeuromorphic computing based on brain-inspired frameworks has shown its potential to perform computation with remarkable power and speed efficiency. The spintronic device has been considered a promising candidate for neuromorphic computing because of its intrinsic non-volatility, ultrafast switching dynamics and scalability. This article will review the current status of neuromorphic computing techniques employing spintronic materials and devices. We will begin with a concise introduction to the biological structure of neurons and then go through several important models of artificial neural networks. The revolutionary breakthroughs of spintronic-based neuromorphic computation will be demonstrated together with their challenges and outlook.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis–apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Zanthoxylum armatum (Z. armatum) is an economic crop widely planted for both spice and medicinal purposes in Southwest China. Soil is a key environmental condition that affects seedling growth and development, and screening suitable soil types is of great significance for the large-scale cultivation of crops. This study designed growth experiments of Z. armatum seedlings in red soil (RS), yellow soil (YS), acidic purple soil (ACPS), alkaline purple soil (ALPS), and alluvial soil (AS) to screen for more suitable soil types. The growth traits of Z. armatum seedlings and the carbon (C), nitrogen (N), phosphorus (P), C:N:P stoichiometry, and non-structural carbohydrate (NSC) content of different organs were comparatively analyzed. The results showed that the morphological indexes of Z. armatum seedlings cultured in AS were better than those in the other four soils.AS and RS may be beneficial for the culture of Z. armatum seedlings due to higher nutrient levels in three organs. Two-factor ANOVA and PCA analysis showed that C, N, and P and their proportions would affect the uptake and distribution of NSC in various organs of Z. armatum seedlings. These results showed that soil types and plant organs significantly affected the accumulation and distribution of N, P, and NSC in Z. armatum seedlings. These results are conducive to screening soil types suitable for the growth and development of Z. armatum and provide data support for further large-scale cultivation of Z. armatum in suitable areas.

The effect of oxygen reduction on the magnetic properties of LaFeO3−δ (LFO) thin films was studied to better understand the viability of LFO as a candidate for magnetoionic memory. Differences in the amount of oxygen lost by LFO and its magnetic behavior were observed in nominally identical LFO films grown on substrates prepared using different common methods. In an LFO film grown on as-received SrTiO3 (STO) substrate, the original perovskite film structure was preserved following reduction, and remnant magnetization was only seen at low temperatures. In a LFO film grown on annealed STO, the LFO lost significantly more oxygen and the microstructure decomposed into La- and Fe-rich regions with remnant magnetization that persisted up to room temperature. These results demonstrate an ability to access multiple, distinct magnetic states via oxygen reduction in the same starting material and suggest LFO may be a suitable materials platform for nonvolatile multistate memory.

Abstract Background and Aim Programmed death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) inhibitors have transformed the treatment landscape of advanced hepatocellular carcinoma (HCC), but consistent responses are not observed in all patients, and prognostic biomarkers to guide treatment decisions are lacking. We aimed to evaluate the predictive value of PD‐L1 expression in advanced HCC patients treated with PD‐1/PD‐L1 inhibitors. Methods A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Studies comparing the objective response rate (ORR) and/or disease control rate (DCR) based on the tumor PD‐L1 status of HCC were included. Results Eleven studies with 1,330 HCC patients treated with PD‐1/PD‐L1 inhibitors were included. Pooled odds ratio (OR) analysis demonstrated a significantly improved ORR in PD‐L1‐positive patients compared with PD‐L1‐negative patients (OR, 1.86, 95% CI, 1.35–2.55). Similar results were observed in the anti‐PD‐1 treatment (p

Abstract Experimental Advanced Superconducting Tokamak (EAST) was built to demonstrate high-power, long-pulse operations under fusion-relevant conditions, with major radius R = 1.9 m, minor radius a = 0.5 m, and design pulse length up to 1000s. It has an ITER-like D-shaped cross-section with two symmetric divertors at the top and bottom, accommodating both single null and double null divertor configurations. EAST construction was started in 2000, and its first plasma was successfully obtained in 2006. In the past 15 years, plasma-facing components, plasma heating, diagnostics, and other systems have been upgraded step by step to meet its mission on exploring of the scientific and technological bases for fusion reactors and studying the physics and engineering technology issues with long pulse steady-state operation. An advanced steady-state plasma operation scenario has been developed, and plasma parameters were greatly improved. Meanwhile, front physics on the magnetic confinement plasmas have been systemically investigated and lots of fruitful results were realized, covering transport and confinement, MHD stabilities, pedestal physics, divertor and scrap-off layer (SOL) physics, and energetic particle physics. This brief review of EAST on engineering upgrading, stand-steady operation scenario development, and plasma physics investigation would be useful for the reference on construction and operation of a superconducting tokamak, such as ITER and future fusion reactor.

Abstract Pinus elliottii used as rootstock instead of homologous rootstock, have been proved to accelerate early growth of the scion (Pinus massoniana), for cultivation of large diameter wood. However, the basal diameter of scions in heterologous grafts was significantly smaller than self-graft 10 years later, according to field investigation, which was opposed to cultivation objectives. Although advantage of heterologous grafts has been reported, less is known about the long term effect of heterologous rootstock on scions of P. massoniana. The aim of present study was to investigate the mechanism of the above difference. Toward this aim, the growth traits and physiological characteristics of scions in the two graft groups were studied, and the underlying mechanism was preliminarily explored through transcriptome sequencing technology. Results showed that scions of heterologous grafts had less TSCA compared to self-grafts, while no significant difference of plant height, number of branches and canopy volume between two graft groups. Besides, scion leaves of heterologous grafts displayed higher antioxidant enzyme activity and lower chlorophyll content. And interactions between rootstocks and scions had also changed the mineral element composition of scion leaves. Compared with homologous grafts, scion leaves of heterologous grafts accumulated more K+, Mg2+ and Zn2+, but less Ca2+,which have been proved to be conducive to the growth of stem diameter of P. massoniana. Moreover, a comparative transcriptome analysis of two graft groups showed that DEGs between them were mainly caused by the specificity of rootstock. GO and KEGG analysis found that heterologous rootstock had different gene expression preferences, and the gene expression level between rootstocks and scions were significantly different, such as auxin auxin-related genes and stress responsive genes. That may imply that auxin pathway played an important role not only in grafting healing process, but also in maintaining the growth between scion and stock. Summary of all above results, we concluded that the long term effect of heterologous rootstock on scions may be unsatisfactory with the later rapidly growth of scion, probably due to delayed graft incompatibility between scion and stock of heterologous grafts. This study may remind us that the long-term growth of the scion deserves attention as well as the healing process, which could also provide a basis for delayed graft incompatibility.

Abstract Background The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis. Methods This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019. Plasma samples were collected before TKI therapy and at tri-monthly intervals thereafter. Genotyping of ctDNA for T790M was performed using a ddPCR EGFR Mutation Assay. Patients were followed up until the date of death or to the end of 2021. Results Seventy-five of 80 patients experienced progressive disease. Fifty-three (71%) of 75 patients underwent rebiopsy, and T790M mutation was identified in 53% (28/53) of samples. Meanwhile, plasma ddPCR detected T790M mutation in 23 (43%) of 53 patients. The concordance rate of T790M between ddPCR and rebiopsy was 76%, and ddPCR identified 4 additional T790M-positive patients. Ten (45%) of 22 patients who did not receive rebiopsy tested positive for T790M by ddPCR. Serial ddPCR analysis showed the time interval from detection of plasma T790M to objective progression was 1.1 (0–4.1) months. Compared to 28 patients with rebiopsy showing T790M, the overall survival of 14 patients with T790M detected solely by ddPCR was shorter(41.3 [95% CI, 36.6–46.0] vs. 26.6 months [95% CI, 9.9–43.3], respectively). Conclusion Plasma ddPCR-based genotyping is a useful technology for detection and monitoring of the key actionable genomic alteration, namely, T790M, in patients treated with gefitinib, erlotinib, or afatinib for activating mutations, to achieve better patient care and outcome.

Abstract Introduction Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. Methods The multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. Results In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p

Abstract To provide high‐quality imaging by decreasing the sparse view imaging artefact from the computed tomography (CT) images, this study addresses a new artefact suppression technique for sparse data for both single material and multi‐material objects that have diverse materials. It begins with a pre‐reconstructed image and a network of target patches that have been trained beforehand and then uses the forward projection (FP) approach to resolve the structural mutation brought on by sparse‐view projection. As an edge‐preserving operator to commit to the forward operator for sinogram correction, the bilateral filter was used. Both simulated and actual data have been gathered and evaluated in experiments. The suggested forward operator and normalized compensation (FONC) method produce results that have far smaller artefact and errors than those of more traditional techniques. For simulation # blade, the Normalized Mean Square Distance (NMSD) of the proposed method was reduced by 8.94%, Structural Similarity Index (SSIM) and the Universal Quality Index (UQI) were increased by 78.17% and 80.49%, respectively, which also demonstrate better uniformity of the results to practical data # pan, where the root mean squared error was reduced by 13.93%. SSIM and UQI were increased by 25.66% and 37.02%, respectively. The results conclusively show that the planned strategies are successful in eliminating artefact for irregular objects.

Probiotics are receiving significant attention due to their considerable health advantages. However, research involving the effect of probiotic biofilm and planktonic cells on the health of the host is limited. This study ascertained that the biofilm cells of Lactiplantibacillus paraplantarum LR-1 displayed stronger immunomodulation activity than their planktonic counterparts. Furthermore, the LR-1 biofilm cells more distinctly influenced the relative abundance of the intestinal marker bacteria than the planktonic cells. In comparison to the planktonic cells and the control group, the biofilm cells exhibited a stronger potential positive effect on the metabolism of the mice. Correlation analysis revealed the interaction between the metabolites, genera, and immune factors, which could explain the mechanism behind the beneficial effect of LR-1 biofilm or planktonic cells on host health. The results of this study enhance the understanding of the beneficial impact of probiotic biofilm cells while providing references for further investigation.

Rhynchanthus beesianus is a medicine food homology plant, and its rhizome is a food spice and traditional Chinese medicine used to treat inflammation-related disorders. Still, little research has been done on its phytochemicals and biological activities. Therefore, this study firstly reported the phytochemical analysis by UHPLC-Q-Orbitrap-MS, antioxidant, anti-enzymatic, and anti-inflammatory effects of R. beesianus rhizome water extract (WE) and 70% ethanol extract (EE). For phytochemical analysis, WE and EE had high total phenolic (25.57–28.19 mg GAE/g extract) and flavonoid (10.57–28.08 mg RE/g extract) contents, and further UHPLC-Q-Orbitrap-MS test identified sixty-one compounds, including twelve phenolic compounds and six flavonoids. In the antioxidant assay, WE and EE showed significant DPPH (IC50: 83.93 ± 5.90 and 69.48 ± 1.57 μg/mL, respectively) and ABTS (IC50: 73.46 ± 0.69 and 40.72 ± 0.67 μg/mL, respectively) radical scavenging ability, especially the efficacy of EE was superior or equivalent to that of positive control BHT. Moreover, the WE and EE exhibited poor inhibition on acetylcholinesterase (IC50: 3.31 ± 0.16 and 3.53 ± 0.14 mg/mL, respectively), butyrylcholinesterase (IC50: 1.29 ± 0.02 and 0.75 ± 0.08 mg/mL, respectively), and tyrosinase (IC50: 5.91 ± 0.63 and 21.30 ± 1.52 mg/mL, respectively). Interestingly, EE showed remarkable inhibition on NO, PGE2, IL-6, and TNF-α produced by LPS stimulation without cytotoxicity. It reduced ROS generation and down-regulated mRNA and protein levels of iNOS and COX-2 in LPS-stimulated RAW264.7 macrophages. Besides, EE decreased LPS-stimulated MAPKs (ERK, p38, and JNK) phosphorylation and inhibited NF-κB p65 nuclear translocation by suppressing the phosphorylation and degradation of IκBα. Therefore, R. beesianus can be used as a promising natural antioxidant, enzyme inhibitor, and anti-inflammatory agent with great exploitation potential in functional food and pharmaceuticals.