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There is increasing interest in the alpha polytype of Ga2O3 because of its even larger bandgap than the more studied beta polytype, but in common with the latter, there is no viable p-type doping technology. One option is to use p-type oxides to realize heterojunctions and NiO is one of the candidate oxides. The band alignment of sputtered NiO on α-Ga2O3 remains type II, staggered gap for annealing temperatures up to 600°C, showing that this a viable approach for hole injection in power electronic devices based on the alpha polytype of Ga2O3. The magnitude of both the conduction and valence band offsets increase with temperature up to 500°C, but then are stable to 600°C. For the as-deposited NiO/ α-Ga2O3 heterojunction, ΔEV=-2.8 eV and ΔEC= 1.6 eV, while after 600°C annealing the corresponding values are ΔEV=-4.4 eV and ΔEC= 3.02 eV. These values are 1-2 eV larger than for the NiO/β-Ga2O3 heterojunction.

NiO/ β-(Al x Ga1-x )2O3 /Ga2O3 heterojunction lateral geometry rectifiers with diameter 50-100 µm exhibited maximum reverse breakdown voltages >7kV, showing the advantage of increasing the bandgap using the β-(Al x Ga1-x )2O3 alloy. This Si-doped alloy layer was grown by Metal Organic Chemical Vapor Deposition with an Al composition of ~21 %. On state resistances were in the range 50-2180 Ω.cm2, leading to power figures-of-merit up to 0.72 MW.cm-2. The forward turn-on voltage was in the range 2.3-2.5 V, with maximum on/off ratios >700 when switching from 5V forward to reverse biases up to -100V. Transmission line measurements showed the specific contact resistance was 0.12 Ω.cm2. The breakdown voltage is among the highest reported for any lateral geometry Ga2O3-based rectifier.

The Chinese writing system is different from English in that individual words both comprise one to four characters and are not separated by clear word boundaries (e.g., interword spaces). These differences raise the question of how readers of Chinese know where to move their eyes to support efficient lexical processing? The widely accepted

In this study, the focused ion beam (FIB) Ga+ irradiation damage on β-Ga2O3 Schottky diode structure under different ion energies were tested, and the effective recovery of diode characteristics after rapid thermal annealing (RTA) post-annealing were also studied. β-Ga2O3 based Schottky diodes have attracted increasing attention because of the prospects for use in next-generation high-power electronics. Focused ion beam (FIB) machining is one of the newest processing techniques, which is mainly used in semiconductor and chip manufacture and transmission electron microscopy (TEM) sample preparation. During FIB sample preparation, the energetic Ga ions are incident onto the sample to induce physical sputtering of the material, which in turn, modifies its chemical composition, crystallinity and electrical properties. It has been found in many studies that 20-30 nm amorphous layer can form on silicon after irradiation with 30 keV Ga ions. From our previous study, the FIB ion beam induced damages could cause significant degradation on diode on-resistance and turn-on voltage. Milling at lower energy has been used to reduce the electrical damage. However low energy milling is more time consuming and less precise. Short-time, high-temperature post-annealing treatments, such as RTA has been proved could remove the crystal damage. Thus, there is a great need to determine the maximal ion beam energy and post-annealing temperature for FIB without degrading diode characteristics. In this work, energies ranging from 2 keV to 30 keV were employed to mill off a part of Ga2O3 epi-layer and Schottky diodes were fabricated on milled surface. Forward IV characteristic shows less degradations with lower ion beam energies. For the diodes exposed to 2, 5, and 10 keV Ga+ ion beams exhibited significant recovery of diode on resistance and turn-on voltage after 300°C RTA annealing. For the diodes exposed to 30 keV Ga+ ion beams recovered significantly after 400 °C annealing. In conclusion, decreasing the FIB energy shows effective alleviations on the FIB damage, and post annealing treatment effectively recovered the damage from Ga+ implantation. This is the first time the thermal annealing treatment was performed for Ga2O3 Schottky diode recovering from FIB cutting, it is an effective and simple way to mitigate the degradation, especially for higher ion beam energies. This work could broaden the FIB’s usability and release tremendous potential as a specimen preparation and imaging tool in materials science applications. Figure 1

Vertical geometry NiO/β n-Ga2O/n+ Ga2O3 heterojunction rectifiers with contact sizes from 50 to 200 μm diameter showed breakdown voltages (VB) up to 7.5 kV for drift region carrier concentration of 8 × 1015 cm−3. This exceeds the unipolar 1D limit for SiC and was achieved without substrate thinning or annealing of the epi layer structure. The power figure-of-merit, VB2/RON, was 6.2 GW cm−2, where RON is the on-state resistance (9.3–14.7 mΩ cm2). The average electric field strength was 7.56 MV/cm, approaching the maximum for β-Ga2O3. The on–off ratio switching from 5 to 0 V was 2 × 1013, while it was 3 × 1010–2 × 1011 switching to 100 V. The turn-on voltage was in the range 1.9–2.1 V for the different contact diameters, while the reverse current density was in the range 2 × 10−8–2 × 10−9 A cm−2 at −100 V. The reverse recovery time was 21 ns, while the forward current density was >100 A/cm2 at 5 V.

NiO/β-Ga2O3 vertical rectifiers exhibit near-temperature-independent breakdown voltages (VB) of >8 kV to 600K. For 100 µm diameter devices, the power figure of merit (VB)2/ RON, where RON is the on-state...

Type 2 diabetes (T2D) increases the risk of coronavirus disease (COVID-19). This study investigates the association between glucose control of COVID-19 patients with T2D in first 7 days after hospital admission and prognosis. A total of 252 infected inpatients with T2D in China were included. Well-controlled blood glucose was defined as stable fasting blood glucose (FBG) levels in the range of 3.9–7.8 mmol/L during first 7 days using indicators of average (FBGA), maximum (FBGM) or first-time (FBG1) FBG levels. The primary endpoint was admission to intensive care unit or death. Hazard ratio (HR) of poorly controlled glucose level group compared with well-controlled group were 4.96 (P = 0.021) for FBGM and 5.55 (P = 0.014) for FBGA. Well-controlled blood glucose levels in first 7 days could improve the prognosis of COVID-19 inpatients with diabetes.

Polyunsaturated fatty acid (PUFA) and eicosapentaenoic acid (EPA) are essential for the health of aquatic organisms and human beings. In order to optimize the culture conditions of Chaetoceros lorenzianus, effects of different iron sources (FeC6H5O7, FeCl3, FeSO4) and different iron concentrations (0.10 mg L− 1, 0.25 mg L− 1, 0.50 mg L− 1, 0.75 mg L− 1, 1.00 mg L− 1, 1.25mg L− 1) on C. lorenzianus were studied. The results showed that different iron sources and different iron concentrations had significant effects on the biomass, chlorophyll A, total lipid and fatty acids of C. lorenzianus (P 4 and FeC6H5O7, FeCl3 had better effects on the growth, chlorophyll a, total lipids, and n-3 PUFA (EPA and DHA) content of C. lorenzianus. The optimum concentration of FeCl3 for the growth and synthesis of chlorophyll a in C. lorenzianus was 0.75–1 mg L− 1, and the optimum concentration for lipid accumulation was 0.25 mg L− 1. The secondary culture method can be used in large-scale culture, that is, the initial culture is performed under the optimal iron concentration (0.75mg L− 1 FeCl3) for obtaining higher biomass, and then, the subsequent culture is performed under a low iron concentration(0.25 mg L− 1 FeCl3) to accumulate higher total lipids.

Patients with Alzheimer’s disease have difficulty maintaining independent living abilities as the disease progresses, causing an increased burden of care on family caregivers and the healthcare system and related financial strain. This patient group is expected to continue to expand as life expectancy climbs. Current diagnostics for Alzheimer’s disease are complex, unaffordable, and invasive without regard to diagnosis quality at early stages, which urgently calls for more technical improvements for diagnosis specificity. Optical coherence tomography or tomographic angiography has been shown to identify retinal thickness loss and lower vascular density present earlier than symptom onset in these patients. The retina is an extension of the central nervous system and shares anatomic and functional similarities with the brain. Ophthalmological examinations can be an efficient tool to offer a window into cerebral pathology with the merit of easy operation. In this review, we summarized the latest observations on retinal pathology in Alzheimer’s disease and discussed the feasibility of retinal imaging in diagnostic prediction, as well as limitations in current retinal examinations for Alzheimer’s disease diagnosis.

Introduction As the pandemic progresses, the pathophysiology of COVID-19 is becoming more apparent, and the potential for tocilizumab is increasing. However, the clinical efficacy and safety of tocilizumab in the treatment of COVID-19 patients remain unclear. Methods To assess the efficacy and safety of tocilizumab treatment in COVID-19 patients, we performed a retrospective case-control study. The study was conducted, including 95 patients treated with tocilizumab plus standard treatment and matched controls with 95 patients treated with standard treatment therapy by propensity score from February to April 2020. We searched some databases using the search terms for studies published from January 1, 2020, to June 1, 2021. Results Our case-control study found a lower mortality rate in the tocilizumab treatment group than in the standard treatment group (9.47% versus 16.84%, P = 0.134), but the results were not statistically significant. We also found that the mortality rate in tocilizumab treatment groups was significantly lower than in the standard treatment group in the stratified ICU analysis (OR 0.52, 95% CI 0.44–0.61, P = 0.048 and OR 0.31, 95% CI 0.10–0.99, P = 0.044). We selected 49 studies (including 6568 cases and 11,660 controls) that met the inclusion criteria in the meta-analysis. In the overall analysis, we performed a meta-analysis that showed significantly decreased mortality after patients received tocilizumab (OR 0.81, 95% CI 0.69–0.95, P = 0.008). We also revealed significant associations within some subgroups. The sequential trial analysis showed a true-positive result. No significant associations were observed between tocilizumab and elevated secondary infection risk, discharge, adverse events, and mechanical ventilation in the overall analysis. Conclusion Tocilizumab significantly decreased mortality in COVID-19 patients with no increased discharge, secondary infection risk, adverse events, and mechanical ventilation in a meta-analysis. Our data suggest that clinicians should pay attention to tocilizumab therapy as an effective and safe treatment for COVID-19 patients.

Innate immunity is the first and essential line for resisting pathogens, and the immune intensity and duration need to be strictly regulated to balance excessive or insufficient immune response. MicroRNAs (miRNAs) are crucial regulators of immune response in Drosophila, yet how immune-related miRNAs are regulated remains poorly understood. Herein, we elucidated that the involvement of miR-317 in NF-κB transcription factor Relish mediated Drosophila Imd pathway in response to Gram-negative (G-) bacteria stimulation. Remarkably, the dynamic expression profiling for immune response indicated that Relish simultaneously enhances the expression of the effector antimicrobial peptide Dpt as well as miR-317 post-infection. Upregulation of miR-317 could further down-regulate the expression of PGRP-LC, thereby forming a feedback in Drosophila Imd pathway to prevent over-activation and restore immune homeostasis. Taken together, our study not only uncovers a novel Relish/miR-317/PGRP-LC regulatory axis to attenuate Drosophila Imd immune response and facilitate immune homeostasis restoration, but also provides vital insights into the complex mechanisms of animal innate immune regulation.

This study aims to investigate the metabolic phenotype and mechanism of 40% calorie restriction (CR) in mice.CR mice exhibit super-stable blood glucose, as evidenced by increased fasting blood glucose (FBG), decreased postprandial blood glucose, and reduced glucose fluctuations. Additionally, both fasting plasma insulin and the homeostasis model assessment of insulin resistance increase significantly in CR mice. Compared with control, the phosphorylation of insulin receptor substrates-1 and serine/threonine kinase decreases in liver and fat but increases in muscle of CR mice after insulin administration, indicating hepatic and adipose insulin resistance, and muscle insulin sensitization. CR reduces visceral fat much more than subcutaneous fat. The elevated FBG is negatively correlated with low-level fasting β-hydroxybutyrate, which may result from insufficient free fatty acids and diminishes ketogenic ability in CR mice. Furthermore, liver glycogen increases dramatically in CR mice. Analysis of glycogen metabolism related proteins indicates active glycogen synthesis and decomposition. Additionally, CR elevates plasma corticosterone and hypothalamic orexigenic gene expression.CR induces lipid insufficiency and stress, resulting in global physiological insulin resistance except muscle and enhances glycogen metabolism, culminating in the stability of blood glucose manifests in increased FBG, which compensates for insufficient blood ketones.

The objective of this research was to quantify the effect of surface degradation and abrasion separately and in combination on the flexural strength of lithia disilicate ceramics. Lithia disilicate disks were fabricated using the lost wax technique and pressing in vacuum. The eight groups in this pilot experiment were (i) reference, hydrated in distilled water for 24 h prior to fracture; (ii) reference, non-hydrated group; (iii) 28-day pH cycling group; (iv) 125K chewing cycle group; (v) combined pH cycling + 125K chewing cycle; (vi) constant pH 2 solution for 28 days; (vii) constant pH 7 solution for 28 days; and (viii) constant pH 10 solution for 28 days. pH cycling is a method that alternates between pH 2, 7 and 10 over 28 days. A total of 15 disks were used for each group. All the groups were tested using the biaxial piston and a three-ball flexural strength test to obtain their biaxial flexural strength. pH 2 constant immersion demonstrated the highest fracture strength and was significantly greater than all other groups (p < 0.0001). Chewing and pH cycling + chewing groups exhibited the lowest fracture strengths and were significantly lower than all other groups (p < 0.0001). The damage observed from the chewing simulator does not represent apparent clinical fractures.

Epigenetic alterations contributed to human carcinogenesis immensely. N6-methyladenosine (m6A) is one of the most preventive and abundant modifications on RNA molecules present in eukaryotes. However, the biological function of m6A methylation in colorectal cancer (CRC) remains largely unclear. Here, we found that METTL14 was downregulated in CRC tissues and cell lines, and closely correlated with overall survival (OS). METTL14 knockdown significantly reduced m6A levels in total RNAs and promoted CRC cell growth and metastasis, whereas METTL14 overexpression markedly increased m6A levels in total RNA and inhibited CRC cell growth and metastasis. Furthermore, we demonstrated that miR-375 was a downstream target of METTL14. We also verified that METTL14 suppressed CRC cell growth via the miR-375/Yes-associated protein 1 (YAP1) pathway, as well as inhibited CRC cell migration and invasion through the miR-375/SP1 pathway. Taken together, our studies showed an important role for METTL14 in CRC progression and provided novel insight into m6A modification in CRC progression., Graphical Abstract, In this study, Wang et al. showed that METTL14, a key factor involved in m6A modification of RNA, interacts with DGCR8 and enhances primary miR-375 (primiR-375) processing in an m6A-dependent manner, thus revealing an important role for METTL14 in CRC progression and providing insight into the role of m6A modification in CRC progression.

Serous ovarian carcinoma (SOC) is a common malignant tumor in female reproductive system. Long noncoding RNA (lncRNA) LIFR-AS1 is a tumor suppressor gene in colorectal cancer, but its effect and underlying mechanism in SOC are still unclear. Therefore, this study focuses on unveiling the regulatory mechanism of LIFR-AS1 in SOC.The relationship between LIFR-AS1 expression and prognosis of SOC patients was analyzed by TCGA database and Starbase, and then, the LIFR-AS1 expression in SOC tissues and cells was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Besides, the relationship between LIFR-AS1 and clinical characteristics was analyzed. Also, the effects of LIFR-AS1 on the biological behaviors of SOC cells were measured by Cell Counting Kit-8, colony formation, and wound-healing and Transwell assays, respectively. Western blot and qRT-PCR were employed to determine the protein expressions of genes related to proliferation (PCNA), apoptosis (cleaved caspase-3), epithelial-mesenchymal transition (E-cadherin, N-cadherin, and Snail).LIFR-AS1 was lowly expressed in SOC, which was correlated with the poor prognosis of SOC patients. Low expression of LIFR-AS1 in SOC was associated with the tumor size, clinical stage, lymph node metastasis, and distant metastasis. LIFR-AS1 overexpression promoted the expressions of cleaved caspase-3 and E-cadherin while suppressing the malignant behaviors (proliferation, migration, and invasion) of SOC cells, the expressions of PCNA, N-cadherin, and Snail. Besides, silencing LIFR-AS1 exerted the effects opposite to overexpressed LIFR-AS1.LIFR-AS1 overexpression inhibits biological behaviors of SOC cells, which may be a new therapeutic method.

The energy and beam current dependence of Ga+ focused ion beam milling damage on the sidewall of vertical rectifiers fabricated on n-type Ga2O3 was investigated with 5–30 kV ions and beam currents from 1.3–20 nA. The sidewall damage was introduced by etching a mesa along one edge of existing Ga2O3 rectifiers. We employed on-state resistance, forward and reverse leakage current, Schottky barrier height, and diode ideality factor from the vertical rectifiers as potential measures of the extent of the ion-induced sidewall damage. Rectifiers of different diameters were exposed to the ion beams and the “zero-area” parameters extracted by extrapolating to zero area and normalizing for milling depth. Forward currents degraded with exposure to any of our beam conductions, while reverse current was unaffected. On-state resistance was found to be most sensitive of the device parameters to Ga+ beam energy and current. Beam current was the most important parameter in creating sidewall damage. Use of subsequent lower beam energies and currents after an initial 30 kV mill sequence was able to reduce residual damage effects but not to the point of initial lower beam current exposures.

NiO/β-(Al xGa1− x)2O3/Ga2O3 heterojunction lateral geometry rectifiers with diameter 50–100 μm exhibited maximum reverse breakdown voltages >7 kV, showing the advantage of increasing the bandgap using the β-(Al xGa1− x)2O3 alloy. This Si-doped alloy layer was grown by metal organic chemical vapor deposition with an Al composition of ∼21%. On-state resistances were in the range of 50–2180 Ω cm2, leading to power figures-of-merit up to 0.72 MW cm−2. The forward turn-on voltage was in the range of 2.3–2.5 V, with maximum on/off ratios >700 when switching from 5 V forward to reverse biases up to −100 V. Transmission line measurements showed the specific contact resistance was 0.12 Ω cm2. The breakdown voltage is among the highest reported for any lateral geometry Ga2O3-based rectifier.

Background Increasing evidence suggests a causal link between periodontitis and cognitive disorders. Systemic inflammation initiated by periodontitis may mediate the development of cognitive impairment. Our study aims to investigate the effect of ligature-induced periodontitis on cognitive function and the role of signal transducers and activators of transcription 3 (STAT3) in this process. Materials and methods Ligature-induced periodontitis was established, and the rats were treated intraperitoneally with/without the pSTAT3 inhibitor cryptotanshinone (CTS). Alveolar bone resorption and periodontal inflammation were detected by micro-computed tomography analysis and histopathological evaluation. Locomotor activity and cognitive function were evaluated by the open field test and the Morris water maze test, respectively. The activation of microglia and astrocytes in the hippocampus and cortex was assessed by immunohistochemistry (IHC). The expression of interleukins (IL-1β, IL-6, IL-8, IL-21) in both the periphery and cortex was evaluated by RT-PCR and ELISA. The expression of TLR/NF-κB and ROS cascades was evaluated by RT-PCR. The expression of pSTAT3 and the activation of the STAT3 signaling pathway (JAK2, STAT3, and pSTAT3) in the periodontal tissue and cortex were assessed by IHC and Western blot. The expression of amyloid precursor protein (APP) and its key secretases was evaluated by RT-PCR. The level of amyloid β-protein (Aβ) and the ratio of Aβ1-40/1-42 were measured via ELISA in the plasma and cortex while IHC was used to detect the level of Aβ1-42 in the brain. Results In periodontal ligature rats, significant alveolar bone resorption and local inflammatory cell infiltration were present. Apparent increases in inflammatory cytokines (IL-1β, IL-6, IL-8, and IL-21) were detected in peripherial blood and brain. Additionally, spatial learning and memory ability was impaired, while locomotor activity was not affected. Activated microglia and astrocytes were found in the cortex and hippocampus, presenting as enlarged cell bodies and irregular protrusions. Levels of TLR/NF-kB, PPAR and ROS were altered. The STAT3 signaling pathway was activated in both the periodontal tissue and cortex, and the processing of APP by β- and γ-secretases was promoted. The changes mentioned above could be relieved by the pSTAT3 inhibitor CTS. Conclusions Ligature-induced periodontitis in rats resulted in systemic inflammation and further abnormal APP processing, leading to cognitive impairments. In this progress, the activation of the STAT3 signaling pathway may play an important role by increasing inflammatory load and promoting neuroinflammation.

This article describes the protocol for determining the cause of failure for retrieved failed implant supported fixed dental prostheses (FDPs) in a clinical study of three-unit bridges. The results of loading of flexure bars of different veneer compositions at different stress rates were presented for two veneer materials (leucite reinforced and fluorapatite glass-ceramic veneers) and a Y-TZP core zirconia ceramic used in the clinical study. From these results, the strengths of the fast loading conditions were used to determine the fracture toughness of these materials. Fractal dimension measurements of the flexure bars and selected FDPs of the same materials demonstrated that the values were the same for both the bars and the FDPs. This allowed the use of fracture toughness values from the flexure bars to determine the strengths of the FDPs. The failure analysis of clinically obtained FDP replicates to determine the size of the fracture initiating cracks was then performed. Using the information from the flexure bars and the size of the fracture initiating cracks for the failed FDPs, the strengths of the FDPs were determined. The clinical failures were determined to be most likely the result of repeated crack growth due to initial overload and continuous use after initial cracking.

BackgroundInfection with SARS-CoV-2 has been associated with liver dysfunction, aggravation of liver burden, and liver injury. This study aimed to assess the effects of liver injuries on the clinical outcomes of patients with COVID-19.MethodsA total of 1,564 patients with severe or critical COVID-19 from Huoshenshan Hospital, Wuhan, were enrolled. Chronic liver disease (CLD) was confirmed by consensus diagnostic criteria. Laboratory test results were compared between different groups. scRNA-seq data and bulk gene expression profiles were used to identify cell types associated with liver injury.ResultsA total of 10.98% of patients with severe or critical COVID-19 developed liver injury after admission that was associated with significantly higher rates of mortality (21.74%, pp+ cells in these tissues. By generating a model, we were able to predict the risk and severity of liver injury during hospitalization.ConclusionWe demonstrate that liver injury occurring during therapy in patients with COVID-19 is significantly associated with the severity of disease and mortality, but the presence of CLD is not associated. We provide a risk-score model that can predict whether patients with COVID-19 will develop liver injury or proceed to higher risk stages during subsequent hospitalizations. These findings may prove beneficial for the clinical management of patients infected with SARS-CoV-2.

Backgrounds: It's well known that calorie restriction (CR) brings striking benefits in metabolic improvement with complex and unclear mechanism. In this study, we aimed to investigate the specific manifestation and possible mechanisms of metabolism in CR mice. Methods: B6 mice were randomly assigned to three groups: (1) chow diet (control) , (2) chow diet with 40% calorie restriction (CR) , (3) high-fat diet (HFD) . The metabolism status and related examination were performed after 12 weeks of feeding. Results: In this study, we found that CR increased fasting blood glucose and plasma insulin, as well as reduced insulin sensitivity reflected by insulin tolerance test. Comparing to the control mice, the decrease of phosphorylation levels of IRS-1 including serine307 and tyrosine632 residues, and AKT (threonine308) after insulin rejection further confirmed that CR induced insulin resistance. Different from insulin resistance induced by HFD, CR improved glucose tolerance and reduced gluconeogenesis. Meanwhile, CR led to absolute lipid reduction, manifested in decreased plasma lipid, liver lipid deposition and fat mass. In contrast, liver glycogen increased dramatically. Fasting glycogen was twice as much as that of HFD group and 20 times as that of control group. Furthermore, the CR increased p-PYGL, p-GSK3β and decreased p-GS notably indicating active glycogen synthesis and decomposition. Subsequently, we found that CR increased plasma corticosterone and decreased plasma c-reactive protein (CRP) compared with control and HFD groups, while plasma corticosterone and CRP in HFD were higher than those in control group. Additionally, CR lowered levels of orexigenic neuropeptides and elevated levels of anorexigenic neuropeptides. Conclusions: Our study suggested that CR induced lipid insufficiency and stress from starvation, resulting in physiological insulin resistance and enhanced glycogen metabolism, including increased glycogen synthesis, glycogenolysis and glycogen content. Disclosure L.Hu: None. X.Xia: None. Y.Gu: None. J.Yin: None. Funding National Natural Science Foundation of China (No. 82070885) ,Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No. 20172025)

Aims: Low-carbohydrate diet (LCD) , characterized by low consumption of carbohydrate and high intake of fat, is well known to decrease body weight and blood glucose in humans. However, in animal experiments, high-fat diet (HFD) is widely used to induce dietary obese model with metabolic disorders. The study aims to explore why LCD/HFD has the opposite effects on humans and animals. Methods: Twenty-two adults with overweight or obesity were enrolled to receive LCD for three weeks. The subjects were divided into two groups according to whether carbohydrate intake is below 10% by calories, and their weight loss and glucose homeostasis were compared. C57 mice were randomly assigned to five groups: chow diet (CD) , HFD with respectively 60%, 70% and 75% fat (cocoa butter) by calories and 60% fat (lard) by calories (60%HFD-L) , and metabolism of mice was evaluated. Results: In this trial, subjects who consumed less carbohydrate had greater weight loss and better glycemic control compared with the others. The questionnaires revealed that most of the subjects favored high-carbohydrate (HC) food rather than low-carbohydrate food. However, in mice, HFD groups showed more weight gain and higher blood glucose compared with CD group. When provided with CD and HFD at the same time, mice ate little CD. Besides, we found HFD group had lower mRNA level of Npy and Agrp and higher mRNA level of Pomc and Cartpt in hypothalamus in comparison with CD group. Among HFD with coco butter groups, mice took in more calories and gained more weight as the fat content in diet increases. Compared with HFD with coco butter groups, mice in 60%HFD-L group consumed even more calories, and had heavier body weight and poorer glucose metabolism. Conclusion: LCD has opposite effects on metabolism in humans and mice because of different food preferences. People prefer HC food while mice favor HFD. Mice consume more and feel less hungry when the diet contains higher proportion of fat, which leads to poorer metabolic status. Besides, mice prefer lard to coco butter. Disclosure X.Xia: None. L.Cai: None. Y.Gu: None. J.Yin: None. Funding National Natural Science Foundation of China (No. 82070885) ,Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No. 20172025)

The characteristics of COVID-19 patients with autoimmune rheumatic diseases (AIRD) have rarely been reported. Patients with AIRD have suppressed immune defense function, which may increase their susceptibility to COVID-19. However, the immunosuppressive agents AIRD patients routinely used may be beneficial for protecting the cytokine storm caused by SARS-CoV-2. In this retrospective study, we included all confirmed cases in Huoshenshan Hospital from February 4 to April 9. Data were extracted from electronic medical records and were analyzed for clinical and laboratory features using SPSS (version 25.0). Of 3059 patients, 21 had the comorbidities with systematic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA), including 5 with SLE, 15 with RA, and 1 with Rhupus. The proportion was 57.1% for severe cases, 61.9% for either severe or critical cases, and 4.8% for critical cases. The main manifestations, ARDS and ICU admission rate, as well as the mortality and length of hospital stay of COVID-19 in AIRD patients were similar to COVID-19 patients in the general population. Our preliminary experience shows that patients with AIRD tend to have a higher risk of SARS-CoV-2 infection, and may be at risk for a severe but less likely critical disease course. Further investigation is needed to understand the immunological features of these diseases.

Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development., Understanding antibody responses to Sars-CoV-2 proteins over time is complicated by many variables. Here the authors survey IgM and IgG antibodies against S protein, RBD and nucleoprotein in a large cohort of infected and recovering severe vs. moderate COVID-19 patients, comparing against clinical parameters and immunological readouts.

Background Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. Case presentation We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. Conclusion When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.

The discovery of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the outbreak of coronavirus disease 2019 (COVID‐19) are causing public health emergency. A handful of literatures have summarized its clinical and radiologic features, whereas therapies for COVID‐19 are rather limited. In order to evaluate the efficacy of convalescent plasma therapy in COVID‐19 patients, we did this timely descriptive study. 6 laboratory confirmed COVID‐19 patients were enrolled and received the transfusion of ABO‐compatible convalescent plasma. The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground glass opacities (GGOs) and consolidation in patient #1, #2, #3, #4 and #6. In patient #1 and #5 who presented with SARS‐CoV‐2 in throat swab, convalescent plasma therapy elicited an elimination of virus. Serologic analysis indicated an immediate increase in anti‐SARS‐CoV‐2 antibody titers in patient #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID‐19. This intervention has a special significance for eliminating SARS‐CoV‐2 and is believed to be a promising state‐of‐art therapy during COVID‐19 pandemic crisis. This article is protected by copyright. All rights reserved.

For centuries, attempts have been continuously made to artificially reconstitute counterparts of in vivo organs from their tissues or cells. Only in the recent decade has organoid technology as a whole technological field systematically emerged and been shown to play important roles in tissue engineering. Based on their self-organizing capacities, stem cells of versatile organs, both harvested and induced, can form 3D structures that are structurally and functionally similar to their in vivo counterparts. These organoid models provide a powerful platform for elucidating the development mechanisms, modeling diseases, and screening drug candidates. In this review, we will summarize the advances of this technology for generating various organoids of tissues from the three germ layers and discuss their drawbacks and prospects for tissue engineering.

In the current issue of Blood, Xia et al evaluate the use of convalescent plasma for the treatment of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19).1,2 SARS-CoV-2 has spurred a global crisis. To date, there are limited treatment options for COVID-19 and no proven prophylactic therapies for those who have been exposed to SARS-CoV-2.

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

The SARS-CoV-2 pandemic has had a significant impact worldwide. Currently, the most common detection methods for the virus are polymerase chain reaction (PCR) and lateral flow tests. PCR takes more than an hour to obtain the results and lateral flow tests have difficulty with detecting the virus at low concentrations. In this study, 60 clinical human saliva samples, which included 30 positive and 30 negative samples confirmed with RT-PCR, were screened for COVID-19 using disposable glucose biosensor strips and a reusable printed circuit board. The disposable strips were gold plated and functionalized to immobilize antibodies on the gold film. After functionalization, the strips were connected to the gate electrode of a metal-oxide-semiconductor field-effect transistor on the printed circuit board to amplify the test signals. A synchronous double-pulsed bias voltage was applied to the drain of the transistor and strips. The resulting change in drain waveforms was converted to digital readings. The RT-PCR-confirmed saliva samples were tested again using quantitative PCR (RT-qPCR) to determine cycling threshold (Ct) values. Ct values up to 45 refer to the number of amplification cycles needed to detect the presence of the virus. These PCR results were compared with digital readings from the sensor to better evaluate the sensor technology. The results indicate that the samples with a range of Ct values from 17.8 to 35 can be differentiated, which highlights the increased sensitivity of this sensor technology. This research exhibits the potential of this biosensor technology to be further developed into a cost-effective, point-of-care, and portable rapid detection method for SARS-CoV-2.

There is increasing interest in α-polytype Ga2O3 for power device applications, but there are few published reports on dielectrics for this material. Finding a dielectric with large band offsets for both valence and conduction bands is especially challenging given its large bandgap of 5.1 eV. One option is HfSiO4 deposited by atomic layer deposition (ALD), which provides conformal, low damage deposition and has a bandgap of 7 eV. The valence band offset of the HfSiO4/Ga2O3 heterointerface was measured using x-ray photoelectron spectroscopy. The single-crystal α-Ga2O3 was grown by halide vapor phase epitaxy on sapphire substrates. The valence band offset was 0.82 ± 0.20 eV (staggered gap, type-II alignment) for ALD HfSiO4 on α-Ga0.2O3. The corresponding conduction band offset was −2.72 ± 0.45 eV, providing no barrier to electrons moving into Ga2O3.

Perovskite quantum dots (PQDs) are extremely unstable in ambient air due to their inherent structural instability, which limits the wide application of PQDs. In this work, silicon-coated CsPbBr

NiO/Ga2O3 heterojunction rectifiers were exposed to 1 Mrad fluences of Co-60 γ-rays either with or without reverse biases. While there is a small component of Compton electrons (600 keV), generated via the interaction of 1.17 and 1.33 MeV gamma photons with the semiconductor, which in turn can lead to displacement damage, most of the energy is lost to ionization. The effect of the exposure to radiation is a 1000× reduction in forward current and a 100× increase in reverse current in the rectifiers, which is independent of whether the devices were biased during this step. The on–off ratio is also reduced by almost five orders of magnitude. There is a slight reduction in carrier concentration in the Ga2O3 drift region, with an effective carrier removal rate of −1. The changes in electrical characteristics are reversible by application of short forward current pulses during repeated measurement of the current–voltage characteristics at room temperature. There are no permanent total ionizing dose effects present in the rectifiers to 1 Mad fluences, which along with their resistance to displacement damage effects indicate that these devices may be well-suited to harsh terrestrial and space radiation applications if appropriate bias sequences are implemented to reverse the radiation-induced changes.

The characteristics of sputtered NiO for use in pn heterojunctions with Ga2O3 were investigated as a function of sputtering parameters and postdeposition annealing temperature. The oxygen/ nickel and Ni2O3/NiO ratios, as well as the bandgap and resistivity, increased as a function of O2/Ar gas flow ratio. For example, the bandgap increased from 3.7 to 3.9 eV and the resistivity increased from 0.1 to 2.9 Ω cm for the O2/Ar ratio increasing from 1/30 to 1/3. By sharp contrast, the bandgap and Ni2O3/NiO ratio decreased monotonically with postdeposition annealing temperatures up to 600 °C, but the density of films increased due to a higher fraction of NiO being present. Hydrogen is readily incorporated into NiO during exposure to plasmas, as delineated by secondary ion mass spectrometry measurements on deuterated films. The band alignments of NiO films were type II-staggered gaps with both α- and β-Ga2O3. The breakdown voltage of NiO/β-Ga2O3 heterojunction rectifiers was also a strong function of the O2/Ar flow ratio during deposition, with values of 1350 V for 1/3 and 830 V for 1/30.