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Abstract Background Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. Methods From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. Results In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P

Abstract Background Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. Methods BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. Results MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. Conclusions MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.

Abstract Long noncoding RNA MYLK antisense RNA 1 (MYLK‐AS1) is the crux in multiple diseases. Therefore, the purpose of this study was to investigate the possible mechanism of MYLK‐AS1. A total of 62 colon cancer (CC) specimens and paired adjacent normal tissues were collected, and the expression of MYLK‐AS1, microRNA (miR)‐101‐5p/cell division cycle 42 (CDC42) was detected. CC cell lines were transfected with MYLK‐AS1, miR‐101‐5p, CDC42‐related plasmids, and the biological functions and markers of epithelial‐mesenchymal transition (EMT) were analyzed. The binding relationship between MYLK‐AS1, miR‐101‐5p, and CDC42 was evaluated. In CC tissues and cell lines, MYLK‐AS1 and CDC42 were highly expressed, and miR‐101‐5p was lowly expressed. Inhibition of MYLK‐AS1 or upregulation of miR‐101‐5p can inhibit CC cell growth and EMT. miR‐101‐5p inhibited CDC42/N‐wasp axis activation in CC cells by targeting CDC42. Knockdown of CDC42 or upregulation of miR‐101‐5p partially reversed the effects caused by upregulation of MYLK‐AS1. MYLK‐AS1, which is significantly upregulated in CC, may be a molecular sponge for miR‐101‐5p, and MYLK‐AS1 promotes the activation of the CDC42/N‐wasp axis in CC cells by targeting CDC42 through miR‐101‐5p, which in turn promotes tumor development. MYLK‐AS1 may be a potential biomarker and target for CC therapy.

ObjectiveThis study aimed to investigate the knowledge, attitude, and practice (KAP) regarding disinfection and hand hygiene, along with associated influencing factors among childcare facilities staff during the COVID-19 pandemic in Anhui, and to provide information for developing disinfection and hand hygiene strategies for childcare facilities.MethodsA web-based cross-sectional study was conducted among Anhui Province residents in China in September 2020. In this study, 60 childcare facilities in two cities of Anhui Province were selected using the convenient sampling method for questionnaires. The questionnaires were distributed through a web-based platform. The disinfection and hand hygiene KAP scores among childcare facilities staff were calculated, and their influencing factors were analyzed. The accuracy rates of knowledge, attitude, and practice of behavior were calculated and analyzed.ResultsA total of 1,029 participants were included in the study. The disinfection and hand hygiene knowledge, attitude and practice ranged from approximately 5 to 23, 1 to 5, 3 to 13, respectively. The score of urban areas was higher than that of rural areas. Higher education levels and more years of working were associated with higher scores. Additionally, staff who received training or supervision had higher scores than those without. The categories with the lowest knowledge accuracy rate (46.3%), lowest attitude accuracy rate (4.2%), and “always” practice rate (5.3%) among childcare facility staff were all related to the question categories concerning the appropriate range of disinfectants for use. The accuracy rates of hand hygiene knowledge and attitude among the childcare facility staff were high (83.7%-99.6%), but the “always” practice rate was in the middle range (63.0%).ConclusionThe disinfection and hand hygiene knowledge among childcare facilities staff was inadequate during the COVID-19 pandemic in Anhui. Continuous implementation of education and training, particularly in rural areas, is essential. Establishing a monitoring system to assess usage effectiveness and adverse reactions in China is critical. Interventions should focus on increasing compliance with hand hygiene practices. Further research should explore the training and intervention of disinfection and hand hygiene, the safety of disinfection measures, and more operational hand hygiene methods in childcare facilities.

Background. gcrR gene acts as a negative regulator related to sucrose-dependent adherence in S. mutans. It is constructive to test the potential capacity of mutans with gcrR gene deficient in bacteria replacement therapy. Methods. In this study, we constructed the mutant by homologous recombination. The morphological characteristics of biofilms were analyzed by confocal laser scanning microscopy. S. mutans UA159 and the mutant MS-gcrR-def were inoculated, respectively, or together for competitive testing in vitro and in rat model. Results. Adhesion assay showed that the adhesion ability of the mutant increased relative to the wild type, especially in the early stage. MS-gcrR-def out-competed S. mutans UA159 in vitro biofilm, and correspondingly coinfection displayed significantly fewer caries in vivo. The former possessed both a lower level of acid production and a stronger colonization potential than S. mutans UA159. Conclusion. These findings demonstrate that MS-gcrR-def appears to be a good candidate for replacement therapy.

Gut dysbiosis, a well-known risk factor to triggers the progression of Alzheimer's disease (AD), is strongly associated with metabolic disturbance. Trimethylamine N-oxide (TMAO), produced in the dietary choline metabolism, has been found to accelerate neurodegeneration in AD pathology. In this study, the cognitive function and gut microbiota of TgCRND8 (Tg) mice of different ages were evaluated by Morris water maze task (MWMT) and 16S rRNA sequencing, respectively. Young pseudo germ-free (PGF) Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type (WT) mice were selected to determine the role of the gut microbiota in the process of neuropathology. Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions. Our results showed that gut dysbiosis, neuroinflammation response, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and cyclin-dependent kinase 5 (CDK5)/transcription 3 (STAT3) activation occurred in Tg mice age-dependently. Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice, with the activation of CDK5/STAT3 signaling in the brains. On the contrary, faecal microbiota transplantation from WT mice alleviated the cognitive deficits, attenuated neuroinflammation, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice. Moreover, excessive choline treatment was also shown to aggravate the cognitive deficits, Aβ deposition, neuroinflammation and CDK5/STAT3 pathway activation. These findings provide a novel insight into the interaction between gut dysbiosis and AD progression, clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy.Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed.Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05).Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.

Organoselenium compounds have attracted significant research interest because of their potent therapeutic activities and indispensable applications in the organic chemistry field. The selenation reactions conventionally rely on the use of sensitive Se reagents; thus, new synthetic methods with improved efficiency and operational simplicity have recently been of particular interest. In this manuscript, we report a Rh-catalyzed direct selenium annulation using tractable sodium selenite (Na2SeO3) as the limiting reagent. The selenite species was converted to highly electrophilic SeO(OBz)2 in situ upon treatment with Bz2O, thereby undergoing C–H/N–H double nucleophilic selenation. A series of benzimidates successfully underwent selenation under mild reaction conditions to afford isoselenazole derivatives.

Abstract For linear time varying (LTV) multiple input multiple output (MIMO) systems with vector relative degree, an open‐closed‐loop iterative learning control (ILC) strategy is developed in this article, where the time interval of operation is iteration dependent. To compensate the missing tracking signal caused by iteration dependent interval, the feedback control is introduced in ILC design. As the tracking signal of many continuous iterations is lost in a certain interval, the feedback control part can employ the tracking signal of current iteration for compensation. Under the assumption that the initial state vibrates around the desired initial state uniformly in mathematical expectation sense, the expectation of ILC tracking error can converge to zero as the number of iteration tends to infinity. Under the circumstance that the initial state varies around the desired initial state with a bound, as the number of iteration tends to infinity, the expectation of ILC tracking error can be driven to a bounded range, whose upper bound is proportional to the fluctuation. It is revealed that the convergence condition is dependent on the feedforward control gains, while the feedback control can accelerate convergence speed by selecting appropriate feedback control gains. As a special case, the controlled system with integrated high relative degree is also addressed by proposing a simplified iteration dependent interval based open‐closed‐loop ILC method. Finally, the effectiveness of the developed iteration dependent interval based open‐closed‐loop ILC is illustrated by a simulation example with two cases on initial state.

Abstract An undescribed pyrrole acid, 1-(4′-methoxy-4′-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages. Graphical abstract

A new species of Primulina, P. pingnanensis, from the Guangxi Zhuangzu Autonomous Region, China, is described and illustrated here. It is morphologically similar to P. orthandra but has significant differences in the bracts, corolla tube and lobes shape, as well as in the indumentum of the outer surface of the corolla, the filaments, the staminodes and the anthers. Colorful photographs and essential information of this new taxon are also provided, including detailed taxonomic description, distribution, habitat, the comparison table, and the IUCN conservation status. We also discuss a validation of new combination P. crassifolia and Chirita crassifolia.

Alzheimer’s disease (AD), an irreversible neurodegenerative disease that progressively impairs memory and cognitive judgment, severely affects the quality of life and imposes a heavy burden on the healthcare system. No cure is currently available for AD, in part because the pathogenesis of this disease has not been established. Animal models are essential for investigating AD pathogenesis and evaluating potential therapeutic strategies for AD. Some phenotypic and neuropathologic changes in AD patients can be recapitulated with genetic and pharmacologic approaches in animals. This article systematically reviews the animal models available for AD research, including transgenic, chemical- or drug-induced, and spontaneous animal models, and the characteristics of these animal models. In this review we also discuss the challenges and constraints when using AD animal models. Although no single animal model can reproduce all pathologic aspects and behavioral features in AD patients, the currently available AD models are valuable tools for deciphering the pathogenic mechanisms underlying AD and developing new anti-AD therapeutics.

Based on the complex aging background, more and more older people have to live in an institution in later life in China. The prevalence of cognitive frailty (CF) is more higher in institutions than in communities. Rarely studies were conducted on the relationship between institutional residence and CF. Hence, this study were performed to determine the relationship between institutional residence (living in a nursing home) and CF in older adults. A total of 1004 older community residents and 111 older nursing home residents over 50 years of age from Hefei, Anhui Province, China were recruited. CF included physical frailty (PF) and mild cognitive impairment (MCI). PF was assessed using the Chinese version of the Fried frailty scale, MCI was assessed using the Montreal Cognitive Assessment, and the common associated factors including sedentary behavior, exercise, intellectual activity, comorbidity, medication, chronic pain, sleep disorders, nutritional status and loneliness were analyzed using regression logistic models. Multivariate regression logistic analysis showed that exercise ( P = .019, odds ratio [OR] = 0.494, 95% confidence interval [CI]: 0.274-0.891), intellectual activity ( P = .019, OR = 0.595, 95% CI: 0.380-0.932), medication use ( P = .003, OR = 2.388, 95% CI: 1.339-4.258), chronic pain ( P = .003, OR = 1.580, 95% CI: 1.013-2.465) and loneliness ( P = .000, OR = 2.991, 95% CI: 1.728-5.175) were significantly associated with CF in community residents; however, only sedentary behavior ( P = .013, OR = 3.851, 95% CI: 1.328-11.170) was significantly associated with CF in nursing home residents. Our findings suggest that nursing homes can effectively address many common risk factors for CF, including lack of exercise and intellectual activity, medication use, chronic pain, and loneliness, better than the community setting. Thus, residing in a nursing home is conducive to the intervention of CF.

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

Abstract Background Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba, exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using the TgCRND8 transgenic AD mouse model, and to explore the underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway. Methods After genotyping to confirm the transgenicity, drug treatments were administered intragastrically once daily to 3-month-old TgCRND8 mice for 4 consecutive months. Several behavioral tests were applied to assess different aspects of neurological functions. Then the brain and colon tissues were harvested for in-depth mechanistic studies. To further verify whether PA exerts anti-AD effects via modulating C/EBPβ/AEP signaling pathway in TgCRND8 mice, adeno-associated virus (AAV) vectors encoding CEBP/β were bilaterally injected into the hippocampal CA1 region in TgCRND8 mice to overexpress C/EBPβ. Additionally, the fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of gut microbiota on the anti-AD effects of PA. Results Our results showed that PA treatment significantly improved activities of daily living (ADL), ameliorated the anxiety-related behavioral deficits and cognitive impairments in TgCRND8 mice. PA modulated the amyloid precursor protein (APP) processing. PA also markedly reduced the levels of beta-amyloid (Aβ) 40 and Aβ42, suppressed Aβ plaque burdens, inhibited tau protein hyperphosphorylation at several sites and relieved neuroinflammation in the brains of TgCRND8 mice. Moreover, PA restored gut dysbiosis and inhibited the activation of the C/EBPβ/AEP signaling pathway in the brain and colon tissues of TgCRND8 mice. Interestingly, PA strikingly alleviated the AD-like pathologies induced by the overexpression of C/EBPβ in TgCRND8 mice. Additionally, the FMT of fecal microbiota from the PA-treated TgCRND8 mice significantly alleviated the cognitive impairments and AD-like pathologies in the germ-free TgCRND8 mice. Conclusion All these findings amply demonstrated that PA could ameliorate the cognitive deficits in TgCRND8 mice via suppressing Aβ plaques deposition, hyperphosphorylation of tau protein, neuroinflammation and gut dysbiosis through inhibiting the activation of C/EBPβ/AEP pathway, suggesting that PA is a promising naturally occurring chemical worthy of further development into the pharmaceutical treatment of AD.

Abstract Purpose To analyse and summarize branching pattern types of the interlobar portion of right pulmonary arteries (RPA) through chest thin-slice CT scans and three-dimensional reconstruction. Methods A total of 179 patients (58 males and 121 females, with an average age of 53.9 years) at the Thoracic Surgery Department of Ningbo First Hospital were retrospectively included from December 2020 to December 2021. All patients completed preoperative thin-slice CT scans and three-dimensional reconstructions of the chest. The clinical data and branching patterns were collected. Data were analysed using SPSS 21.0. Results The branching pattern types of the interlobar portion of RPA were divided into 4 types according to the order and number of branches: Type I (145/179, 81.0%), Asc. A2, MA, A6; Type II (28/179, 15.6%), Asc. A2 deletion, MA, A6; Type III (5/179, 2.8%), Asc. A2, A6, MA; and Type IV (1/179, 0.6%), MA, Asc. A2, A6. Type I was the most common pattern. Furthermore, according to the number of branches of MA and A6, this pattern can be subdivided into 15 subcategories. Conclusion Chest thin-slice CT scans and 3D reconstructions can provide surgeons with accurate lung anatomy, which helps surgeons perform preoperative planning and complete surgery successfully.

Objective To evaluate the application of online-teaching in ultrasound-guided regional block. Methods A total of 356 students (September 2020 to October 2020) who participated in three-phase online teaching in ultrasound-guided regional block were enrolled. Questionnaire regarding the online teaching were distributed to gather the feedback opinions. Results 81.47% of the students responded positively about online-teaching. 71.63% of the students agreed that online-teaching didn't impact their learning experience. 63.82% of the students thought the interactivity of online teaching was satisfying. 59.41% of the students preferred online-teaching to traditional teaching in ultrasound-guided regional block. Conclusions The online-teaching in ultrasound-guided regional block is accepted well by trainers. Further combination of online-teaching and hands-on workshop training may improve the teaching quality by complementary mutual advantages.

2D transition metal ditellurides exhibit nontrivial topological phases, but the controlled bottom-up synthesis of these materials is still challenging. Here, the authors report the layer-by-layer growth of large-area bilayer and trilayer 1T’ MoTe2 films, showing thickness-dependent ferroelectricity and nonlinear Hall effect.

Post-collisional alkaline intrusive rocks from the Dabie orogen were studied for their whole-rock major-trace elements and Sr-Nd-Hf-Pb isotopes, as well as zircon U-Pb ages and Hf-O isotopes. The results provide geochemical constraints on the nature of their mantle sources and thus insight into crust-mantle interaction in the continental collision zone. The alkaline intrusive rocks are composed of syenite and nepheline syenite. Syn-magmatic zircon U-Pb dating by LA-ICP-MS for them yielded Early Cretaceous ages of 131.3 ± 1.4 Ma to 122.6 ± 0.6 Ma, coeval with the post-collisional magmatism in the Dabie orogen. One relict zircon with U-Pb age of 211 Ma is consistent with the timing of metamorphism for the ultrahigh-pressure (UHP) metamorphic rocks in this orogen. They have arc-like trace element distribution patterns, such as enrichment in LILE (large ion lithophile element) and LREE (light rare earth element) but depletion in HFSE (high field strength element), and enriched whole-rock Sr-Nd-Hf isotope compositions with high (87Sr/86Sr)i ratios of 0.7077–0.7131 but negative εNd(t) values of −16.0 to −9.4 and εHf(t) values of −17.5 to −12.7. Their syn-magmatic zircons have three groups of Hf-O isotope compositions comparable to those of UHP metamorphic rocks in Central-South Dabie and North Dabie, which represent the upper and middle continental crust of the subducted South China Block, respectively. In this regard, slab–mantle interaction is evident during the Triassic continental collision. We suggest that the melts derived from the subducted South China Block reacted with the lithospheric mantle wedge of the North China Block, resulting in phlogopite-bearing metasomatites, whose partial melting would generate the post-collisional alkaline intrusive rocks during the Early Cretaceous.

Abstract There have been an increasing number of patients with degenerative disc diseases due to the aging population. In light of this, studies on the pathogenesis of intervertebral disc degeneration have become a hot topic, and gene knockout mice have become a valuable tool in this field of research. With the development of science and technology, constitutive gene knockout mice can be constructed using homologous recombination, zinc finger nuclease, transcription activator‐like effector nuclease technology and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system, and conditional gene knockout mice can be constructed using the Cre/LoxP system. The gene‐edited mice using these techniques have been widely used in the studies on disc degeneration. This paper reviews the development process and principles of these technologies, functions of the edited genes in disc degeneration, advantages, and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene‐edited model mice are presented. At the same time, possible technological improvements in the future are also discussed.

IntroductionPasteurella multocida is a widespread respiratory pathogen in pigs, causing swine pneumonia and atrophic rhinitis, and the capsular serogroups A and D are the main epidemic serogroups in infected animals. This study investigated the protective effects of serogroup A and D bacterins against current circulating P. multocida strains, to better understand the immunity generated by bacterins.Method13 serogroup A (seven A: L3 and six A: L6 strains) and 13 serogroup D (all D: L6 strains) P. multocida strains were isolated, and used as inactivated whole cell antigen to prepare P. multocida bacterins. Mice were immunized with these bacterins at 21-day interval and intraperitoneally challenged with the homologous and heterologous P. multocida strains, respectively. The antibody titer levels and immunization protective efficacy of vaccines were evaluated.ResultsAll of the bacterins tested induced high titer levels of immunoglobulin G antibodies against the parental bacterial antigen in mice. Vaccination with the six A: L6 bacterins provided no protection against the parent strain, but some strains did provide heterologous protection against A: L3 strains. Vaccination with the seven A: L3 bacterins provided 50%–100% protection against the parent strain, but none gave heterologous protection against the A:L6 strains. Immunization with the thirteen D: L6 bacterins offered 60%–100% protection against the parent strain, and almost all D: L6 strains gave cross-protection.DiscussionThis study found that the cross-protectivity of serogroup A strains was poor, while serogroup D strains was effective, which provided some insights for P. multocida vaccine development.

PurposeHead and neck squamous cell carcinoma (HNSCC) ranks sixth among all cancers globally regarding morbidity, and it has a poor prognosis, high mortality, and highly aggressive properties. In this study, we established a model for predicting prognosis based on immunohistochemical (IHC) scores.MethodsData on 402 HNSCC cases were collected, the glmnet Cox proportional hazards model was used, risk factors were analyzed for predicting the prognosis of survival, and the IHC score was established. We used the IHC score to predict disease-free survival (DFS) using training and independent validation cohorts, including 264 cases in total. Additionally, the accuracy of the IHC score and the TNM system (8th edition) was compared. A DFS prediction nomogram was established by combining the prognostic factors.ResultsThe IHC scores included CK, Ki-67, p16, and p40 staining intensity. The concordance index and the Kaplan-Meier survival analysis showed that the IHC scores had high predictive power for HNSCC. Our results showed that the IHC score is an independent factor that can predict prognosis in a multivariate Cox regression analysis. When predicting DFS, the IHC score had a significantly higher value for the area under the ROC curve (AUC) than that of the TNM system. A nomogram was established and included the IHC score, age, tumor location, and the TNM stage. The calibration curves exhibited high consistency between the prognosis predicted by our nomogram and the actual prognosis.ConclusionsThe IHC score was more accurate than the eighth edition of the TNM system in predicting HNSCC prognosis. Therefore, combining the two methods can facilitate individualized patient consultation and care.

Abstract Nitrate, a common pollutant in water, can be used as a nitrogen source for electrocatalytic ammonia production. Bismuth oxide (Bi2O3) is a promising electrocatalyst because of earth‐abundance and high hydrogen overpotential. However, it also has the disadvantages of easy agglomeration and poor charge transfer. This study demonstrated that the high dispersion of Bi2O3 nanosheets can be achieved through in‐situ growth on Ti3C2Tx MXene nanosheets that improved the efficiency of charge transmission, and thus improving the electrocatalytic ammonia production performance. A NH3 yield rate of ∼7.00 mg h−1 cm−2 with faradic efficiency of 91.1 % could be achieved on 11 % Bi2O3/MXene. Density functional theory (DFT) calculations, electrochemical active surface area (ECSA) and electrochemical impedance spectroscopy (EIS) proved that the excellent ammonia production performance came from the fact that bismuth oxide itself could inhibit hydrogen evolution, and in situ growth on MXene enabled high active site exposure and enhanced charge transfer capacity.

Metals such as Cu and Cr have good infrared reflection properties, but there are few reports on their effects on the optical properties of solar spectrum absorption layers. Herein, Cu and Cr infrared reflectors were deposited under AlCrNO absorbing layer by multi arc ion plating technology, and the effects of deposition parameters of infrared reflectors on coating properties were studied. The morphology, element composition and phase structure of the coating were analyzed by scanning electron microscope, energy dispersive spectrometer and X - ray diffraction. Results showed that compared with the coating without infrared reflection layer, the coating with Cu infrared reflection layer had the best performance, the absorptivity was increased by 1.7%, and the emissivity was reduced by 31.9%. Besides, the absorptivity and emissivity of coating with Cr infrared reflector were increased by 0.6% and 13%, respectively. Therefore, Cu was better than Cr as infrared reflector.

The paper presents an improved hybrid tri-stable cantilever piezoelectric energy harvester based on rotational motion, thus providing a new perspective for achieving higher efficiency in energy capture for rotational motion. The proposed system comprises a piezoelectric cantilever beam with an innovative dynamic amplifier installed at the edge of a vehicle's wheel hub. Through theoretical analysis and numerical simulations, the influence of parameters such as the mass of the tip magnetic on the piezoelectric beam, the wheel hub radius, rotational speed, and the ratio of the dynamic amplifier's spring stiffness are investigated with respect to the system's steady-state dynamic response and time-domain performance. A comparative analysis is also conducted with traditional tri-stable piezoelectric energy harvesters. The results demonstrate that the hybrid tri-stable piezoelectric energy harvester exhibits superior performance in capturing vibrational energy during rotational motion, compared to traditional tri-stable piezoelectric energy harvesters. Proper adjustments to the mass of the tip magnetic and the internal spring stiffness of the dynamic amplifier can enhance the system's output voltage and the rotational speed range of inter-well motion. Additionally, the rotational speed range of inter-well motion increases with the expansion of the wheel hub radius. However, when the rotational speed is below 100 rpm, the influence of varying the wheel hub radius on the system's output voltage is minimal. [ABSTRACT FROM AUTHOR]

Polypropylene is commonly used as a binder for ceramic injection molding, and rapid cooling is often encountered during processing. However, the crystallization behavior of polypropylene shows a strong dependence on cooling rate due to its semi-crystalline characteristics. Therefore, the influence of cooling rate on the quality of final product cannot be ignored. In this study, the fast differential scanning calorimetry (FSC) test was performed to study the influence of cooling rate on the non-isothermal crystallization behavior and non-isothermal crystallization kinetics of a copolymer polypropylene (PP BC03B). The results show that the crystallization temperatures and crystallinity decrease as the cooling rate increases. In addition, two exothermic peaks occur when cooling rate ranges from 30 to 300 K·s-1, indicating the formation of another crystal phase. Avrami, Ozawa and Mo equations were used to explore the non-isothermal crystallization kinetics, and it can be concluded that the Mo method is suitable for this study. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, associated with an outcome of hepatic fibrosis/cirrhosis and hepatocellular carcinoma. However, limited exploration of the underlying mechanisms hinders its prevention and treatment. To investigate the mechanisms of epigenetic regulation in NAFLD, the expression profile of circular RNA (circRNA) of rodents in which NAFLD was induced by a high-fat, high-cholesterol (HFHC) diet was studied. Modeling of the circRNA-microRNA (miRNA) -mRNA regulatory network revealed the functional characteristics of NAFLD-specific circRNAs. The targets and effects in the liver of such NAFLD-specific circRNAs were further assessed. Our results uncovered that the downregulation of 28 annotated circRNAs characterizes HFHC diet-induced NAFLD. Among the downregulated circRNAs, long intergenic non-protein coding RNA, P53 induced transcript (LNCPINT) -derived circRNAs (circ_0001452, circ_0001453, and circ_0001454) targeted both miR-466i-3p and miR-669c-3p. Their deficiency in NAFLD abrogated the circRNA-based inhibitory effect on both miRNAs, which further inactivated the AMPK signaling pathway via AMPK-α1 suppression. Inhibition of the AMPK signaling pathway promotes hepatic steatosis, depending on the transcriptional and translational upregulation of lipogenic genes, such as those encoding sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) in hepatocytes. The levels of LNCPINT-derived circRNAs displayed a negative association with hepatic triglyceride (TG) concentration. These findings suggest that loss of LNCPINT-derived circRNAs may underlie NAFLD via miR-466i-3p- and miR-669c-3p-dependent inactivation of the AMPK signaling pathway.

The feasibility of laser‐engineered fluorescence emission from carbon black (CB) with three laser sources of different wavelengths—660 nm (red), 532 nm (green), and 405 nm (blue) is demonstrated. From which the 660 nm focused laser beam produces the most intense fluorescence. Detailed systematic studies on how the laser‐engineered fluorescence emission from CB depends on laser power, laser patterning speed, and environmental control during the laser modification process are carried out. From the systematic studies, the CB samples in ambience undergo most noticeable modifications with a laser power of ≈7 mW and patterning speed of ≈12 μms−1. The fluorescence emission is attributed to the creation of complex defects states into the oxidized form of the pristine system by the formation of 1) C60 fullerene and fullerites; 2) ZnO; 3) Zn2SiO4, and more complex hybrid such as 4) carbon‐induced mid‐gap states in Zn2SiO4, and 5) Ca‐induced defects in ZnO. Such incorporations resulted in the formation of intermediate states in the large bandgap materials. As a result, distinct multicolored fluorescence is emitted by these laser‐quenched material systems. Accordingly, multicolored fluorescence designs can be created with elaborative control of focused laser treatment in an ambient and helium environment.

Seeking a scientific and reasonable population structure is the key to realizing low-carbon and green development of urban agglomerations. Based on the coupled coordination degree model and exploratory spatial data analysis (ESDA), this paper studied the spatiotemporal differences of population spatial equilibrium in Changsha-Zhuzhou-Xiangtan urban agglomeration, and constructed a nonlinear dynamic panel econometric model and quantile regression model to empirically test the carbon emission reduction effect and its heterogeneity of the population spatial equilibrium. The research conclusions are as follows: First, the population spatial equilibrium index of Changsha-Zhuzhou-Xiangtan urban agglomeration shows an upward trend in time, but the overall level is not high and the internal gap is obvious. In space, it presents a situation of concentration in the central urban area of Changsha. Second, the carbon emissions of Changsha-Zhuzhou-Xiangtan urban agglomeration have obvious dynamic inertia and path-dependent characteristics. That is, the carbon emissions of the previous period will significantly promote the carbon emissions of the current period. Third, the carbon emission reduction effect of population spatial equilibrium has the characteristics of an inverted “U” shape, and the population spatial equilibrium index in most areas is too low to achieve carbon emission reduction. Fourth, the legal environment helps to promote the spatial balance of population, thereby reducing the regional total carbon emissions, per capita carbon emissions and carbon emissions per unit area. Last, Changsha-Zhuzhou-Xiangtan urban agglomeration needs to improve the level of economic development and government expenditure to realize the carbon emission reduction effect. In general, Changsha-Zhuzhou-Xiangtan urban agglomeration should take into account the development of economy and environment in the process of improving the level of population space balance, so as to achieve a win-win situation for economy and environment.

Locusta migratoria manilensis is one of the most important agricultural pests in China. The locust has high fecundity and consumes large quantities of food, causing severe damage to diverse crops such as corn, sorghum, and rice. Immunity against pathogens and reproductive success are two important components of individual fitness, and many insects have a trade-off between reproduction and immunity when resources are limited, which may be an important target for pest control. In this study, adult females L. migratoria manilensis were treated with different concentrations (5 × 106 spores/mL or 2 × 107 spores/mL) of the entomopathogenic fungus Paranosema locustae. Effects of input to immunity on reproduction were studied by measuring feeding amount, enzyme activity, vitellogenin (Vg) and vitellogenin receptor (VgR) production, ovary development, and oviposition amount. When infected by P. locustae, feeding rate and phenol oxidase and lysozyme activities increased, mRNA expression of Vg and VgR genes decreased, and yolk deposition was blocked. Weight of ovaries decreased, with significant decreases in egg, length and weight.Thus, locusts used nutritive input required for reproduction to resist invasion by microsporidia. This leads to a decrease in expression of Vg and VgR genes inhibited ovarian development, and greatly decreased total fecundity. P. locustae at 2 × 107 spores/mL had a more obvious inhibitory effect on the ovarian development in migratory locusts. This study provides a detailed trade-off between reproduction and immune input of the female, which provides a reliable basis to find pest targets for biological control from those trade-off processes.

Objective To investigate the training, career development and mental status of anesthesia postgraduates during the pandemic of COVID-19. Methods A self-designed questionnaire was distributed through WeChat platform to anesthesia postgraduates in Beijing, Shanghai and Chengdu. The data were recorded automatically. Results A total of 222 anesthesia postgraduates participated in the survey. Among them, 52.7% of the students were contented with outcomes of online learning, 37.84% of the students considered their graduation were negatively affected by the pandemic, 76.92% of the students thought they were more used to interview in real life than online interview, and 54.95% of the students had psychological counseling service provided by school experts during the pandemic. Conclusions During the COVID-19 pandemic, medical school endeavored to guarantee the study, career development and mental health of postgraduates.

Abstract Memristors are a new type of circuit element with a resistance that is tunable to discrete levels by a voltage/current and sustainable after removal of power, allowing for low‐power computation and multilevel information storage. Many organic‐inorganic lead perovskites are reported to demonstrate memristive behavior, but few have been considered for use as a multilevel memory; also, their potential application has been hindered by the toxicity of lead ions. In this article, lead‐free perovskite MASnBr3 was utilized in memristors for quaternary information storage. Indium tin oxide (ITO)/MASnBr3/Au memristors were fabricated and showed reliable memristive switching with well‐separated ON/OFF states of a maxima resistance ratio of 102 to 103. More importantly, four resistive states can be distinguished and repeatedly written/read/erased with a retention time of 104 seconds and an endurance of 104 pulses. By investigating the current‐electrode area relationship, Br distribution in the ON/OFF states by in situ Raman and scanning electron microscopy, and temperature‐dependent current decay, the memristive behavior was explicitly attributed to the forming/breaking of conductive filaments caused by the migration of Br− under an electric field. In addition, poly(ethylene terephthalate)‐ITO/MASnBr3/Au devices were found to retain their multiresistance state behavior after being bent for 1000 times, thus demonstrating good device flexibility. Our results will inspire more lead‐free perovskite work for multilevel information storage, as well as other memristor‐based electronics.

Abstract Background Long non-coding RNA H19 (lncRNA H19) has been implicated in tumorigenesis and metastasis of breast cancer through regulating epithelial to mesenchymal transition (EMT); however, the underlying mechanisms remain elusive. Methods LncRNA H19 and TNFAIP8 were identified by qRT-PCR and western blotting. CCK-8 assay, clone formation assay, transwell assay, and flow cytometry assay were performed to determine cell proliferation, migration, invasion and cell cycle of breast cancer respectively. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the protein expression levels of p53, TNFAIP8, and marker proteins of EMT cascades in vivo. Dual luciferase reporter assay and RNA pull down assay were conducted to evaluate the interactions of lncRNA H19, p53 and TNFAIP8. Results The expression of lncRNA H19 and TNFAIP8 was up-regulated in breast cancer tissues and cell lines, especially in triple-negative breast cancer (TNBC). Functionally, knockdown of lncRNA H19 or TNFAIP8 coused the capacities of cell proliferation, migration, and invasion were suppressed, and cell cycle arrest was induced, as well as that the EMT markers were expressed abnormal. Mechanistically, lncRNA H19 antagonized p53 and increased expression of its target gene TNFAIP8 to promote EMT process. Furthermore, silencing of lncRNA H19 or TNFAIP8 also could inhibit tumorigenesis and lymph node metastases of MDA-MB-231 cells in xenograft nude mouse models. Conclusions Our findings provide insight into a novel mechanism of lncRNA H19 in tumorigenesis and metastases of breast cancer and demonstrate H19/p53/TNFAIP8 axis as a promising therapeutic target for breast cancer, especially for TNBC.

Abstract Background High-grade glioma (HGG) is a fatal human cancer. Bortezomib, a proteasome inhibitor, has been approved for the treatment of multiple myeloma but its use in glioma awaits further investigation. This study aimed to explore the chemotherapeutic effect and the underlying mechanism of bortezomib on gliomas. Methods U251 and U87 cell viability and proliferation were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, tumor cell spheroid growth, and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry. Temozolomide (TMZ)-insensitive cell lines were induced by long-term TMZ treatment, and cells with stem cell characteristics were enriched with stem cell culture medium. The mRNA levels of interested genes were measured via reverse transcription-quantitative polymerase chain reaction, and protein levels were determined via Western blotting/immunofluorescent staining in cell lines and immunohistochemical staining in paraffin-embedded sections. Via inoculating U87 cells subcutaneously, glioma xenograft models in nude mice were established for drug experiments. Patient survival data were analyzed using the Kaplan–Meier method. Results Bortezomib inhibited the viability and proliferation of U251 and U87 cells in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest. Bortezomib also significantly inhibited the spheroid growth, colony formation, and stem-like cell proliferation of U251 and U87 cells. When administrated in combination, bortezomib showed synergistic effect with TMZ in vitro and sensitized glioma to TMZ treatment both in vitro and in vivo. Bortezomib reduced both the mRNA and protein levels of Forkhead Box M1 (FOXM1) and its target gene Survivin. The FOXM1–Survivin axis was markedly up-regulated in established TMZ-insensitive glioma cell lines and HGG patients. Expression levels of FOXM1 and Survivin were positively correlated with each other and both related to poor prognosis in glioma patients. Conclusions Bortezomib was found to inhibit glioma growth and improved TMZ chemotherapy efficacy, probably via down-regulating the FOXM1–Survivin axis. Bortezomib might be a promising agent for treating malignant glioma, alone or in combination with TMZ.

Both free and glycosidically bound forms of volatile compounds in Vidal grapes from the Shangri-La high-altitude region during the on-vine non-destructive dehydration process were investigated by headspace solid-phase micro-extraction (HS-SPME) combined with gas chromatography–mass spectrometry (GC-MS), following which the data were processed by multivariate statistical analysis. Fatty-acid-derived volatiles (FADs), amino-acid-derived volatiles (AADs), and isoprene-derived volatiles (IPDs), which occurred mainly in bound forms, were the three major volatiles in dehydrated Vidal grapes. Water-loss concentration, biosynthesis, and biodegradation all occurred during dehydration, eventually modifying some volatiles significantly, especially some powerful odorants such as hexanal, trans-2-hexenal, 2-phenethyl acetate, β-myrcene, linalool, geraniol, cis-rose oxide, and β-damascenone. 1-Octen-3-ol was relatively stable during the non-destructive on-vine dehydration process and its content in grape juice was mainly determined by the concentration effect. 2,4-Di-tert-butylphenol, 2-phenethyl acetate, 2-methyl-1-propanol, and hexanol were screened as some of the most important metabolic markers to discriminate grapes at different dehydration degrees. Our study also highlights the fundamental importance of the expression of volatile content in the metabolomic study of grape berries.

Based on real data, a new parameterized model of the Main Drift Chamberresponse is proposed. In this model, we tune the ratio of good hits and theresidual distribution separately. The difference between simulation and data intrack reconstruction efficiency reduces from 1% to 0.5%, and the momentumresolution agreement improves significantly.