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Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo, especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.

Previous studies have shown that functional networks are present at birth and change dynamically throughout infancy and early childhood. However, the status of functional connectivity is still poorly understood in patients with infantile esotropia (IE). The aim of this study is to investigate the developmental trends of functional connectivity in patients with IE during a critical period of growth and development. A total of 17 patients with IE (9 males and 8 females; mean age: 3.36 ± 2.03 years, age range: 0.67–6.36 years) and 20 healthy subjects matched for age and gender were recruited and underwent resting-state functional magnetic resonance imaging. The whole-brain functional network connectivity was analyzed for the IE group and healthy control group. A general linear model was applied to assess the group-age interaction in terms of the functional connectivity. The discrepancy between the two groups in functional connectivity trajectories was also quantified across age and exhibited by the quadratic parabolic model. There were significant group-age interactions between the visual network and the default mode network, the visual network and the sensorimotor network, the limbic network and the default mode network, and within the limbic network in the functional connectivity. A U-shaped tendency across age, with an “inflection point” ranging from 3.1 to 4.0 years of age was exhibited in the difference between functional connectivity trajectories of the IE patients and normal controls. Abnormality in functional network connectivity could present in IE patients at birth, exhibiting aberrant developmental patterns over time. An abnormal functional network could reduce the ability of the cortex in visual information processing, further reactivating the subcortical visual information processing system, which is probably the pathogenesis of IE. Three to four years after birth is the critical time window for children with IE to establish normal network connections in the brain. Early surgery during this period may be helpful for affected children to have an opportunity to approach the normal development trajectory as early as possible.

In this article, we use the two-sided market theory as a support and take the operating data of eight Chinese third-party payment platform companies as samples, based on pricing models and multiple regression analysis, to build a price feature model for a third-party payment platform. The results show that under the two-sided market environment, the scale of consumer and the same-side network externality of the merchant have a negative significant effect on the pricing of the third-party payment platform to the seller; The market share of the platform and the bank fee cost of the platform have a positive significant effect on the pricing of a third-party payment platform to the merchant. At the same time, the same-side network externality of the seller, the scale of a merchant, and the selection of the business model of the platform have no significant effect on the pricing of the third-party payment platform to the merchant. These conclusions provide a scientific basis for a third-party payment platform enterprise to develop an appropriate pricing strategy and operating model.

Submarine groundwater discharge (SGD), including both land-based fresh groundwater that enters the ocean from coastal aquifers as well as recirculated seawater that is continuously recharged and discharged on the seabed, has been considered as an important component of the global water and biogenic element (e.g., nitrogen, phosphorus, silicon and carbon) sources and a significant pathway for material exchange at the land-sea interface of coastal ecosystems. Some researchers reported that SGD associated nutrient additions to coastal waters have caused unwanted ecological issues, including red tides, coastal acidification and hypoxia. Natural radon isotope (222Rn, t1/2 = 3.8 d) is an excellent tracer for studying SGD and other oceanographic processes including air-sea gas exchange, sediment-water diffusion, and earthquake prediction. However, the conventional radon measurement methods suffer many technical disadvantages. We consequently developed a convenient submersible radon determination approach (“OUC-Rn”) using a commercial pulsed ionization chamber (PIC) radon sensor and gas extraction membrane module to produce high precision and high resolution observations. We demonstrate the radon degassing efficiency of the membrane contactor is comparable to the shower-head type air-water exchanger but is independent of operating position. The radon measurement efficiency of the PIC is 2-fold higher than the RAD7 detector and is far less influenced by moisture. We successfully deployed the system in 2.5 meters water depth over a 100 hours period in an anthropogenic influenced bay. Based on our high temporal resolution observations, the SGD flux was estimated to be 0-43.0 cm/d (mean: 25.4 ± 14.5 cm/d). The SGD fluxes pattern plotted together with the tidal variations revealed that tidal pumping may be the main force driving seawater recirculation into aquifers and thus affecting nutrient, carbon and other dissolved matters dynamics in coastal regions.

BackgroundInsomnia is considered one of the manifestations of sleep disorders, and its intensity is linked to the treatment effect or suicidal thoughts. Major depressive disorder (MDD) is classified into various subtypes due to heterogeneous symptoms. Melancholic MDD has been considered one of the most common subtypes with special sleep features. However, the brain functional mechanisms in melancholic MDD with insomnia remain unclear.Materials and methodsMelancholic MDD and healthy controls (HCs, n = 46) were recruited for the study. Patients were divided into patients with melancholic MDD with low insomnia (mMDD-LI, n = 23) and patients with melancholic MDD with high insomnia (mMDD-HI, n = 30), according to the sleep disturbance subscale of the 17-item Hamilton Depression Rating Scale. The dynamic amplitude of low-frequency fluctuation was employed to investigate the alterations of brain activity among the three groups. Then, the correlations between abnormal dALFF values of brain regions and the severity of symptoms were investigated.ResultsLower dALFF values were found in the mMDD-HI group in the right middle temporal gyrus (MTG)/superior temporal gyrus (STG) than in the mMDD-LI (p = 0.014) and HC groups (p < 0.001). Melancholic MDD groups showed decreased dALFF values than HC in the right middle occipital gyri (MOG)/superior occipital gyri (SOG), the right cuneus, the bilateral lingual gyrus, and the bilateral calcarine (p < 0.05). Lower dALFF values than HC in the left MOG/SOG and the left cuneus in melancholic MDD groups were found, but no significant difference was found between the mMDD-LI group and HC group (p = 0.079). Positive correlations between the dALFF values in the right MTG/STG and HAMD-SD scores (the sleep disturbance subscale of the HAMD-17) in the mMDD-HI group (r = 0.41, p = 0.042) were found. In the pooled melancholic MDD, the dALFF values in the right MOG/SOG and the right cuneus (r = 0.338, p = 0.019), the left MOG/SOG and the left cuneus (r = 0.299, p = 0.039), and the bilateral lingual gyrus and the bilateral calcarine (r = 0.288, p = 0.047) were positively correlated with adjusted HAMD scores.ConclusionThe occipital cortex may be related to depressive symptoms in melancholic MDD. Importantly, the right MTG/STG may play a critical role in patients with melancholic MDD with more severe insomnia.

Obesity is a recognized epidemic worldwide, and the accumulation of excess free saturated fatty acids (SFAs) in cells induces cellular lipotoxic damage and increases the risk of a wide spectrum of metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat SFA-induced cellular damage. However, the comparative studies of the two types of unsaturated fatty acids (UFAs) are still limited. We investigated the effects of different MUFAs and PUFAs in the human hepatocyte line L-02 cells in vitro, and in high-fat-diet (HFD)-induced obese C57BL/6 mice in vivo. The results of the in vitro study showed that SFAs induced significant cellular lipotoxic damage, but the combination of MUFAs/PUFAs with SFAs significantly improved the impaired cell viability. Particularly, oleic acid (OA) was superior to eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and arachidonic acid (AA) in terms of its anti-apoptotic effect and inhibition of endoplasmic reticulum (ER) stress. In vivo, both olive-oil-enriched (HFD + OO) and fish-oil-enriched high-fat diets (HFD + FO) reduced hepatic steatosis and improved insulin sensitivity in obese mice. However, FO induced an abnormal increase in serum aspartate aminotransferase (AST) and an increase in the oxidative stress indicator Malondialdehyde (MDA). Liver-targeted lipidomic analysis showed that liver lipid metabolites under the two types of UFA dietary interventions differed from the HFD group, modulating the abundance of some lipid metabolites such as triglycerides (TGs) and glycerophospholipids. Furthermore, the FO diet significantly increased the abundance of the associated FA 20:5 long-chain lipid metabolites, whereas the OO diet regulated the unsaturation of all fatty acids in general and increased the abundance of FA 18:1 in the overall lipid metabolites, especially TGs, which may primarily contribute to the FO, and OO drove protection in NAFLD.

The significance of CO2 emissions at the water–air interface from inland water bodies in the global carbon cycle has been recognized and is being studied more and more. Although it is important to accurately assess CO2 emission flux in a catchment, little research has been carried out to investigate the spatio-temporal variations in CO2 emissions in view of a water continuum. Here, we systematically compared the differences and control factors of CO2 degassing across the water–air interface of a spring–river–lake continuum in the discharge area of Baotuquan Spring in July 2017, which is a typical temperate karst spring area in Jinan city, northern China, using hydrogeochemical parameters, stable carbon isotope values, and CO2 degassing flux. Affected by the pCO2 concentration gradient between the water and ambient air, the spring water showed a high CO2 degassing flux (166.19 ± 91.91 mmol/(m2 d)). After the spring outlet, the CO2 degassing flux in the spring-fed river showed a slight increase (181.05 ± 155.61 mmol/(m2 d)) due to river flow rate disturbance. The river flow rate was significantly reduced by the “blockage” of the lake, which promoted the survival and reproduction of phytoplankton and provided favorable conditions for aquatic plant photosynthesis, increasing the plankton biomass in the lake to 3383.79 × 104/L. In addition, the significant decrease in the dissolved inorganic carbon (DIC) concentration and the increase in the δ13CDIC values in the lake also indicated that the photosynthesis of the lake’s aquatic plants resulted in a significant decrease in the pCO2 concentration, thus limiting the amount of CO2 off-gassing (90.56 ± 55.03 mmol/(m2 d)).

According to the International Energy Agency (IEA) [...]

Magnesium (Mg2+) is the most abundant divalent ion in plants, participating in numerous metabolic processes in growth and development. CorA/MRS2/ALR type Mg2+ transporters are essential for maintaining Mg2+ homeostasis in plants. However, the candidate protein and its potential functions in the tomato plant have not been fully understood. In this study, we identified seven MGT genes (SlMRS2) in tomato based on sequence similarity, domain analysis, conserved motif identification, and structure prediction. Two SlMRS2 genes were analyzed in the bacterial strain MM281, and a functional complementary assay demonstrated their high-affinity transport of Mg2+. Quantitative real-time PCR analysis revealed that the expressions of these Mg2+ transporters were down-regulated in leaves under Mg2+ limitation, with a greater impact on lower and middle leaves compared to young leaves. Conversely, under Mg2+ toxicity, several genes were up-regulated in leaves with a circadian rhythm. Our findings indicate that members of the SlMRS2 family function as Mg2+ transporters and lay the groundwork for further analysis of their distinct functions in tomato.

Grain filling plays an important role in achieving high grain yield. Manipulating planting densities is recognized as a viable approach to compensate for the reduced yield caused by nitrogen reduction. Understanding the effects of nitrogen fertilization and planting density on superior and inferior grain filling is crucial to ensure grain security. Hence, double-cropping paddy field trials were conducted to investigate the effect of three nitrogen levels (N1, conventional nitrogen application; N2, 10% nitrogen reduction; N3, 20% nitrogen reduction) and three planting densities (D1, conventional planting density; D2, 20% density increase; D3, 40% density increase) on grain yield, yield formation, and grain-filling characteristics at two sowing dates (S1, a conventional sowing date, and S2, a date postponed by ten days) in 2019–2020. The results revealed that the annual yield of S1 was 8.5–14% higher than that of S2. Reducing nitrogen from N2 to N3 decreased the annual yield by 2.8–7.6%, but increasing planting densities from D1 to D3 significantly improved yield, by 6.2–19.4%. Furthermore, N2D3 had the highest yield, which was 8.7–23.8% higher than the plants that had received the other treatments. The rice yield increase was attributed to higher numbers of panicles per m2 and spikelets per panicle on the primary branches, influenced by superior grain filling. Increasing planting density and reducing nitrogen application significantly affected grain-filling weight, with the 40% density increase significantly facilitating superior and inferior grain filling with the same nitrogen level. Increasing density can improve superior grains while reducing nitrogen will decrease superior grains. These results suggest that N2D3 is an optimal strategy to increase yield and grain filling for double-cropping rice grown under two sowing-date conditions.

Flavonoids are considered to be critical metabolites in regulating plant responses to abiotic stress. Chalcone synthase (CHS) catalyzes the first key step in the flavonoid biosynthesis pathway. However, there is no in-depth information on the sequence and functional analysis of CHS genes in Dendrobium catenatum. In this study, a total of 14 DcCHS genes were identified, encoding proteins of 349–504 amino acids in length, a protein molecular weight ranging between 39.08 and 56.56 kDa, and isoelectric points from 5.64 to 9.63. The DcCHS proteins were then divided into three groups according to their phylogenetic relationships. The members of each group had similar conserved motifs and gene structures. Quantitative real-time RT-PCR (RT-qPCR) analysis revealed that the DcCHS genes exhibited variable expression patterns in the different plant tissues evaluated. Furthermore, six genes were differentially expressed following exposure to abiotic stresses: DcCHS-6, DcCHS-5/-6, DcCHS-13/-14, and DcCHS-6/-8/-9/-13, which were specifically expressed in response to drought, heat, cold, and salt stress, respectively. This is the first genome-wide analysis of the CHS genes in D. catenatum, and our findings can provide essential information for a better understanding of the function of DcCHS genes, thus facilitating further research on D. catenatum stress tolerance.

Chimeric antigen receptor T cell (CAR-T) therapy in hematologic malignancies has made great progress, but there are still some problems. First, T cells from tumor patients show an exhaustion phenotype; thus, the persistence and function of the CAR-Ts are poor, and achieving a satisfactory curative effect is difficult. Second, some patients initially respond well but quickly develop antigen-negative tumor recurrence. Thirdly, CAR-T treatment is not effective in some patients and is accompanied by severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity. The solution to these problems is to reduce the toxicity and enhance the efficacy of CAR-T therapy. In this paper, we describe various strategies for reducing the toxicity and enhancing the efficacy of CAR-T therapy in hematological malignancies. In the first section, strategies for modifying CAR-Ts using gene-editing technologies or combining them with other anti-tumor drugs to enhance the efficacy of CAR-T therapy are introduced. The second section describes some methods in which the design and construction of CAR-Ts differ from the conventional process. The aim of these methods is to enhance the anti-tumor activity of CAR-Ts and prevent tumor recurrence. The third section describes modifying the CAR structure or installing safety switches to radically reduce CAR-T toxicity or regulating inflammatory cytokines to control the symptoms of CAR-T-associated toxicity. Together, the knowledge summarized herein will aid in designing better-suited and safer CAR-T treatment strategies.

Preeclampsia (PE) is one of the leading causes of maternal death worldwide. Elevated fatty acid binding protein 4 (FABP4) levels have been observed in patients with PE, however, the mechanism by which FABP4 contributes to the pathogenesis of PE remains unclear. In this study, we compared the levels of FABP4 and cytokines between 20 PE patients and 10 healthy pregnant women by using ELISA, immunohistochemistry (IHC) analysis, and flow cytometry (fluorescence-activated cell sorting, FACS). Elevated FABP4 was accompanied by regulatory T (Treg)/T helper type 17 (Th17) imbalance in PE. Knockdown of FABP4 attenuated lipopolysaccharide (LPS)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-17A (IL-17A) production in primary macrophages. In addition, silencing of FABP4 also suppressed Th17 differentiation via paracrine signaling. Overexpression of FABP4 promoted Th17 differentiation via increasing IL-17A/IL-23 release. Reciprocally, IL-17A upregulated FABP4 and activated the NLRP3 inflammasome in vitro and in vivo. The in vivo studies revealed that FABP4 inhibitor BMS309403 ameliorated PE clinical phenotypes, the Treg/Th17 imbalance, and NLRP3 inflammasome activation in PE mice model. In conclusion, FABP4 facilitates inflammasome activation to induce the imbalance of Treg/Th17 in PE via forming a positive feedback with IL-17A.

Hereditary tyrosinemia type I (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury (LLI). Therapeutic options for HT1 remain limited. The FAH−/− pig, a well-characterized animal model of HT1, represents a promising candidate for testing novel therapeutic approaches to treat this condition. Here, we report an improved single-step method to establish a biallelic (FAH−/−) mutant porcine model using CRISPR-Cas9 and cytoplasmic microinjection. We also tested the feasibility of rescuing HT1 pigs through inactivating the 4-hydroxyphenylpyruvic acid dioxygenase (HPD) gene, which functions upstream of the pathogenic pathway, rather than by directly correcting the disease-causing gene as occurs with traditional gene therapy. Direct intracytoplasmic delivery of CRISPR-Cas9 targeting HPD before intrauterine death reprogrammed the tyrosine metabolism pathway and protected pigs against FAH deficiency-induced LLI. Characterization of the F1 generation revealed consistent liver-protective features that were germline transmissible. Furthermore, HPD ablation ameliorated oxidative stress and inflammatory responses and restored the gene profile relating to liver metabolism homeostasis. Collectively, this study not only provided a novel large animal model for exploring the pathogenesis of HT1, but also demonstrated that CRISPR-Cas9-mediated HPD ablation alleviated LLI in HT1 pigs and represents a potential therapeutic option for the treatment of HT1.

Abstract Soil degradation has been found in urban forests in Shanghai, especially in the pure plantations. Mixed plantations are considered to improve soil quality because they can stimulate organic matter cycling and increase soil carbon and nutrient content. Although soil microbes play crucial roles in regulating soil biogeochemical processes, little is known about how mixed plantations affect soil microbial communities, including bacteria, archaea, and fungi. Here, we evaluated soil chemical properties, abundances and compositions of soil bacterial, archaeal, and fungal communities, and enzyme activities in pure and mixed Metasequoia glyptostroboides and Bischofia polycarpa plantations, located in Shanghai, China. The results showed that soil available phosphorus content in the mixed plantation of M. glyptostroboides and B. polycarpa was significantly higher than that in pure plantations, while no significant difference was observed in the content of soil organic carbon, total and available nitrogen, total and available potassium among the three studied plantations. We found higher fungal abundance in the mixed plantation, when compared to both pure plantations. Moreover, fungal abundance was positively correlated with the content of soil available phosphorus. No significant difference was found in the abundance and diversity of bacterial and archaeal community among the three studied plantations. A similarity analysis (ANOSIM) showed that mixed plantation significantly altered the community composition of archaea and fungi, accompanied with an increase of alkaline phosphatase activity. However, ANOSIM analysis of bacterial communities showed that there was no significant group separation among different plantations. Overall, results from this study indicated that fungal and archaeal communities were more sensitive to aboveground tree species than bacterial community. Moreover, mixed plantations significantly increased the activity of alkaline phosphatase and the content of soil available phosphorus, suggesting that afforestation with M. glyptostroboides and B. polycarpa is an effective way to alleviate phosphorus deficiency in urban forests in Shanghai, China.

Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for severe RSV infection is highest in infants and older adults. A safe and effective RSV vaccine for older adults represents a serious unmet medical need due to higher morbidity and mortality in this age group. In this randomized, partially double-blind, placebo-controlled, phase 1 dose-escalation study, we evaluated the safety, tolerability and immunogenicity of an investigational messenger ribonucleic acid (mRNA) vaccine encoding the RSV fusion protein (F) stabilized in the prefusion conformation. The study was conducted in healthy younger adults (ages ≥18 and ≤49 years) and healthy older adults (ages ≥60 and ≤79 years). Participants received mRNA-1777 (V171) or placebo as a single intramuscular dose. For each dose level, three sentinel participants were administered open-label mRNA-1777 (V171). Seventy-two younger adults were randomized and administered 25, 100, or 200 µg mRNA-1777 (V171) or placebo, and 107 older adults were randomized and administered 25, 100, 200 or 300 µg mRNA-1777 (V171) or placebo. Primary objectives were safety and tolerability and secondary objectives included humoral and cell-mediated immunogenicity. All dose levels of mRNA-1777 (V171) were generally well tolerated and no serious adverse events related to the vaccine were reported. Immunization with mRNA-1777 (V171) elicited a humoral immune response as measured by increases in RSV neutralizing antibody titers, serum antibody titers to RSV prefusion F protein, D25 competing antibody titers to RSV prefusion F protein, and cell-mediated immune responses to RSV-F peptides.

Abstract Aim To explore the experience of dealing with defecation dysfunction by changing the eating behaviours of people with rectal cancer following sphincter‐saving surgery. Design The descriptive qualitative design was applied. Methods Individual semi‐structured interviews were conducted with 36 purposively selected rectal cancer survivors who had experienced sphincter‐saving surgery. All interviews were recorded and transcribed verbatim. The thematic analysis was used to structure the data analysis. Results Three major themes, namely “have motivations to change diet”; “need strategies to change diet” and “face barriers to change diet” were generated along with 12 subthemes. Overall, needing to change one's dietary behaviour is the most important theme in addressing defecation dysfunction in patients following sphincter‐saving surgery. Future studies need to focus more on the specific relationship between different food types and the degree of defecation dysfunction. Systematic, scientific and continuous instructions on eating behaviour are in great need for patients after sphincter‐saving surgery.

Abstract Changes that occur to the stem cell microenvironment with disease are a major consideration that may affect the behavior and potential therapeutic efficacy of mesenchymal stem cells (MSCs). The purpose of this study is to evaluate the effects of adipose-derived MSCs (ADSCs) from obese mice with hyperglycemia on body weight and glucose homeostasis. After 10 weeks of high-fat diet, mice were injected with phosphate-buffered saline (PBS) and ADSCs derived from normal mice (N-ADSCs) or obese mice (O-ADSCs), respectively. Mice fed with standard rodent chow were injected with PBS and served as normal controls. Obese mice treated with O-ADSCs showed less body weight gain than those receiving PBS or N-ADSCs. The mice that received ADSCs, especially O-ADSCs, also showed improvement in obesity-related hyperglycemia. In particular, the inguinal fat was reduced in obese mice receiving O-ADSCs compared with other groups, probably caused by the increased lipolysis of inguinal fat. Moreover, ADSC infusion restored insulin receptor (INSR) expression in the muscle of obese mice. Differential expression of the CD90 surface marker was slightly increased, while monocyte chemoattractant protein 1 (MCP-1) was reduced in O-ADSCs compared to N-ADSCs. These data provide a theoretical basis that autologous ADSCs from obese individuals may be more effective for treating obesity and related hyperglycemia.

Abstract STAG3 is essential for male meiosis and testis of male Stag3 −/− mice shows the histopathological type of germ cell maturation arrest (MA). Whether variants of the STAG3 gene exist in Chinese idiopathic non-obstructive azoospermia (NOA) patients needs to be determined. We recruited 58 Chinese NOA men with MA who underwent testis biopsy and 192 fertile men as the control group. The 34 exons of the STAG3 gene were amplified using polymerase chain reaction (PCR) and sequenced. We identified eight novel single nucleotide polymorphisms (SNPs), including two missense SNPs (c.433T > C in exon2 and c.553A > G in exon3), three synonymous SNPs (c.539G > A, c.569C > T in exon3, and c.1176C > G in exon8), and three SNPs in introns. The allele and genotype frequencies of the novel and other SNPs have no significant differences between two groups. Our results indicated that variants in the coding sequence of the STAG3 gene were uncommon in NOA patients with MA in Chinese population. Future studies in large cohorts of different ethnic populations will be needed to determine the association between the STAG3 gene and NOA.

Caerulomycins and collismycins are two types of 2,2’-bipyridine natural products that are biosynthesized via a hybrid NRPS-PKS pathway, but the details of their biosynthesis were unknown. Here, the authors elucidate their biosynthetic pathways, validate the generality of 2,2’-bipyridine formation, and clarify the process for 2,2’-bipyridine furcation.

BackgroundBlood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure.MethodsThoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism.ResultsAfter microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group.ConclusionThe gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.

Prostate cancer is one of the most common malignant tumors in men. Pyroptosis is related to tumor immune infiltration and tumor microenvironment (TME) and has been confirmed to be related to the progression of a variety of tumors. However, the relationship between prostate cancer and pyroptosis, as well as TME and tumor immune infiltration, has not been discussed yet. We obtained and combined the RNA-seq data of prostate cancer from TCGA and GEO databases, analyzed the differential expression of pyroptosis-related genes (PRGs), and divided them into two groups according to the PRG expression level. The relationship between pyroptosis subtypes and the TME of prostate cancer was further verified, and the differential expression genes (DEGs) in the two subtypes were identified. The relationship between the DEGs and clinicopathology was explored and KEGG and GO enrichment analysis was conducted; it was found that most DEGs were enriched in immune-related pathways. Then, we randomly divided datasets into training and testing sets, performed the LASSO and multicox progression analysis, selected eight genes as prognostic signatures and used the eight genes, calculated the risk score, and then separated the entire cohort into high- and low-risk groups. The prognosis between two groups and the 1-, 3-, and 5-year ROC curves of biochemical relapse (BCR) were verified in training, testing, and the entire cohort, respectively. The TME, CSC index, mutation, and drug susceptibility were also discussed.

BackgroundActive surveillance (AS) has been considered the first-line management for patients with clinical low-risk papillary thyroid microcarcinoma (PTMC) who often have lymph node micrometastasis (m-LNM) when diagnosed. The “low-risk” and “high prevalence of m-LNM” paradox is a potential barrier to the acceptance of AS for thyroid cancer by both surgeons and patients.MethodsPatients diagnosed with PTMC who underwent thyroidectomy with at least one lymph node (LN) examined were identified from a tertiary center database (n = 5,399). A β-binomial distribution was used to estimate the probability of missing nodal disease as a function of the number of LNs examined. Overall survival (OS) probabilities of groups with adequate and inadequate numbers of LNs examined were estimated using the Kaplan–Meier method in the Surveillance, Epidemiology, and End Results (SEER) database (n = 15,340). A multivariable model with restricted cubic splines was also used to verify the association of OS with the number of LNs examined.ResultsThe risk of residual m-LNM (missed nodal disease) ranged from 31.3% to 10.0% if the number of LNs examined ranged from 1 and 7 in patients with PTMC. With 7 LNs examined serving as the cutoff value, the intergroup comparison showed that residual positive LNs did not affect OS across all patients and patients aged ≥55 years (P = 0.72 and P = 0.112, respectively). After adjusting for patient and clinical characteristics, the multivariate model also showed a slight effect of the number of LNs examined on OS (P = 0.69).ConclusionsEven with the high prevalence, OS is not significantly compromised by persistent m-LNM in the body of patients with low-risk PTMC. These findings suggest that the concerns of LNM should not be viewed as an obstacle to developing AS for thyroid cancer. For patients with PTMC who undergo surgery, prophylactic central LN dissection does not provide a survival benefit.

Emotion regulation in childhood and adolescence is related to their social development. Better emotion regulation is associated with great individual academic performance and mental health. However, compared with the research on emotion regulation strategies, children’s automatic emotion regulation has been less investigated. Using event-related potential (ERP) technology, this study adopts the cued-emotion Go/Nogo paradigm to investigate the processing characteristics of automatic emotion regulation in children aged 8–12 years. The current study selected 34 younger group [16 boys, 18 girls, mean (M) ± SD = 8.91 ± 0.75], and 31 older group [18 boys, 13 girls, M ± SD = 11.26 ± 0.45]. The results showed that, for Nogo trials, the amplitude of N2 and P3 evoked by emotional faces were significantly larger than those evoked by neutral faces, reflecting the cognitive conflict experienced and the process of children’s automatic response inhibition to emotional stimuli, respectively. However, no significant difference in N2 and P3 amplitude were found in Go trials, which may indicate that children aged 8–12 showed similar top-down control and similar motivated attention in this experiment, respectively. Further analysis found that the negative affect of temperament was significantly positively correlated with Nogo-P3 induced by neutral pictures (r = 0.37, p < 0.001), and preadolescents’ social anxiety was significantly positively correlated with Nogo-P3 followed by neutral pictures (r = 0.31, p < 0.01). These findings can provide inspiration and empirical support for the promotion and intervention of emotion regulation in children and adolescents.

ObjectiveThis study aims to evaluate the impact of the inferior petrosal veins (IPVs) on operational exploration and to analyze related anatomic features.MethodsA total of 317 patients were retrospectively studied. Surgical outcomes and postoperative complications were analyzed, and patients were divided into two groups according to whether the IPV was sacrificed or preserved. The diameter of the IPV was also recorded during operation. Furthermore, the position where the IPV drained into the jugular bulb was recorded in each patient, and the influence of different injection points on the operation was analyzed.ResultsIPVs were conclusively identified in 242/317 (76.3%) of patients, with 110/242 (45.5%) of patients categorized as “IPV sacrifice” versus 132/242 (54.5%) categorized as “IPV preservation.” IPV diameter was observed to be 1 mm in 39 cases (16.2%). The position of IPV drainage into the jugular bulb was at the level of the accessory nerve in 163 cases (67.3%), the level of the vagus nerve in 42 cases (17.4%), and the level of the glossopharyngeal nerve or above in 37 cases (15.3%). The diameters of IPV in the sacrifice group were mainly less than 1 mm (94.5% vs. 75%, P 1 mm.

Escherichia coli is a gram-negative bacterium that is distributed widely throughout the world; it is mainly found in contaminated food, the poultry industry, and animal feces. The emergence of antibiotic-resistant E. coli poses a threat to human and animal health, which has led to renewed interest in phage-based therapy. E. coli biofilm control and prevention are of great importance. In this study, the isolated phages Flora and KM18 were found to belong to the family Myoviridae; the optimal preservation buffer was pH = 6~7, and the phage genome sizes were 168,909 (Flora) and 168,903 (KM18) bp. Phage Flora had a broader lytic spectrum than KM18. Phage Flora had a better antibiofilm effect than kanamycin sulfate in high-concentration E. coli cultures. A combination of the phage Flora and kanamycin sulfate showed better antibiofilm effects than Flora or kanamycin sulfate alone in low-concentration E. coli cultures. These characteristics can serve as a guideline for the selection of effective candidates for phage therapy, in this case antibiotic-resistant E. coli control in the poultry industry.

ObjectiveThis study develops a group of service capability indicators for long-term care facilities to assess their current conditions and makes it the first step toward the improvement of service capability in China.MethodsWe constructed an initial indicator framework based on the characteristics of long-term care services and a literature review. Potential indicators were collected, and a 2-round modified web-based Delphi process was conducted by a national multidisciplinary expert panel to construct a service capability evaluation index system. The accepted competencies of indicators were established with mean scores in all three scoring criteria (importance, feasibility, and sensitivity) ≥ 4.0, consensus rate reached 70.0%, and a coefficient of variation ≤ 0.25.ResultsA new indicator framework covering 2 dimensions of inputs and activities was developed in this study. The initial 35 indicators formed an indicator pool for the Delphi questionnaire. According to the final consensus of the expert panel, the Delphi consultation resulted in an index system comprised 31 tertiary indicators across six subdimensions (i) staffing; (ii) facilities and equipment; (iii) funding; (iv) medical inspection services; (v) health management services; (vi) institutional standard management.ConclusionThis study developed a set of indicators suitable for the long-term care system in China and is expected to be applied to measure and improve the service capability of long-term care facilities. In addition, these indicators can be used for comparisons between different LTCFs and provide an evidence basis for the further development of capability assessment tools.

In this study, dynamic variations in physicochemical characteristics of polysaccharides from ‘Wuyi rock’ tea (WYP) at different simulated digestion and fecal fermentation stages in vitro were studied. Results revealed that physicochemical characteristics of WYP were slightly altered after the simulated digestion in vitro, and its digestibility was about 8.38%. Conversely, physicochemical characteristics of the indigestible WYP, including reducing sugar, chemical composition, constituent monosaccharide, molecular weight, and FT-IR spectrum, were obviously altered after the fecal fermentation in vitro, and its fermentability was about 42.18%. Notably, the indigestible WYP could remarkably modulate the microbial composition via promoting the proliferation of profitable intestinal microbes, such as Bacteroides, Lactococcus, and Bifidobacterium. Moreover, it could also enhance the generation of short-chain fatty acids. The results showed that WYP was slightly digested in the gastrointestinal tract in vitro, but could be obviously utilized by intestinal microbiota, and might possess the potential to improve intestinal health.

ObjectiveThe purpose of this study was to evaluate the safety, efficiency, and cost expenditure of remote programming in patients with Parkinson's disease (PD) after deep brain stimulation (DBS).MethodsA total of 74 patients who underwent DBS at the Department of Neurosurgery, Zhongnan Hospital of Wuhan University between June 2018 and June 2020 were enrolled in this study. There were 27 patients in the remote programming group and 47 patients in the outpatient programming group. Clinical data, programming efficiency, adverse events, expenditure, and satisfaction were compared between the two groups.ResultsA total of 36 times of remote programming were performed on the 27 patients in the remote programming group, and four had mild adverse events during programming, and the adverse events disappeared within 1 week. The satisfaction questionnaire showed that 97.3% of the patients were satisfied with the surgical effect. The patients in the remote programming group (88.9%) were more likely to receive long-term programming after DBS than the patients in the outpatient programming group (74.5%). The Parkinsonism symptoms improved in both programming groups. The majority (18/27) of patients in the remote programming group lived away from the programming center, while the majority (27/47) of patients in the outpatient programming group lived in Wuhan, where the programming center was located (P = 0.046). The cost per patient per programming was US$ 43.5 in the remote programming group and $59.5 (56–82.7) in the outpatient programming group (P < 0.001). The median time cost for each visit was 30 min (25–30) in the remote programming group and 150 min (135–270.0) in the outpatient programming group (P < 0.001).ConclusionRemote programming is safe and effective after DBS in patients with Parkinson's disease. Moreover, it reduces expenditure and time costs for patients and achieves high satisfaction, particularly for patients living far from programming centers.

Considering its speedy development and extremely low 5-year overall survival rate worldwide, bladder cancer (BCa) is one of the most common and highly malignant tumors. Increasing evidence suggests that protein-coding mRNAs and non-coding RNAs, including long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs), play an essential role in regulating the biological processes of cancer. To investigate the molecular regulation associated with poor prognosis during advanced BCa development, we constructed a competitive endogenous RNA (ceRNA) network. Using transcriptome profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, we performed differential expression (DE) analysis, weighted gene co-expression network analysis, functional enrichment analysis, survival analysis, prediction of miRNA targeting, and Pearson correlation analysis. Through layers of selection, 8 lncRNAs-28 mRNAs and 8 miRNAs-28 mRNAs pairs shared similar expression patterns, constituting a core ceRNA regulatory network related to the invasion, progression, and metastasis of advanced clinical stage (ACS) BCa. Subsequently, we conducted real time qPCR, western blotting, and immunohistochemistry to validate expression trend bioinformatics analysis on 3, 2, and 3 differentially expressed mRNAs, lncRNAs, and miRNAs, respectively. The most significantly differentially expressed LINC01929, miR-6875-5p and ADAMTS12 were selected for in vitro experiments to assess the functional role of the LINC01929/miR-6875-5p/ADAMTS12 axis. RNA pull-down, luciferase assays, and rescue assays were performed to examine the binding of LINC01929 and miR-6875-5p. Increasing trends in COL6A1, CDH11, ADAMTS12, LINC01705, and LINC01929 expression variation were verified as consistent with previous DE analysis results in ACS-BCa, compared with low clinical stage (LCS) BCa. Expression trends in parts of these RNAs, such as hsa-miR-6875-5p, hsa-miR-6784-5p, COL6A1, and CDH11, were measured in accordance with DE analysis in LCS-BCa, compared with normal bladder urothelium. Through experimental validation, the cancer-promoting molecule ADAMST12 was found to play a key role in the development of advanced BCa. Functionally, ADAMTS12 knockdown inhibited the progression of bladder cancer. Overexpression of LINC01929 promoted bladder cancer development, while overexpression of miR-6785-5p inhibited bladder cancer development. Mechanistically, LINC01929 acted as a sponge for miR-6785-5p and partially reversed the role of miR-6785-5p. Our findings provide an elucidation of the molecular mechanism by which advanced bladder cancer highly expressed LINC01929 upregulates ADAMTS12 expression through competitive adsorption of miR-6875-5p. It provides a new target for the prognosis and diagnosis of advanced bladder cancer.

BackgroundDietary management was an important strategy for controlling low anterior resection syndrome (LARS) after sphincter-saving surgery, however, the influencing dietary factors of LARS are not completely clear. This study aims at exploring the specific association between perioperative intake of foods and nutrients and the improvement of LARS within the first 6 months after surgery.MethodsThis study applied a prospective cohort design. 210 consecutive patients were admitted in the colorectal surgical ward after the sphincter-saving surgery in a tertiary hospital in China from May to November in 2020. The perioperative food intake was assessed by the food frequency questionnaire, and the bowel symptoms were assessed by the Low Anterior Resection Syndrome Score Scale. The binary logistic regression was used to analyze the collected data.ResultsIt was found out that both the intake of oil before surgery and at 6 months after surgery were significantly associated with the improvement of LARS. The average daily intake of livestock and poultry meats and oil during the first 6 months after sphincter-saving surgery were also associated with the improvement of LARS.ConclusionsThe relationship between the intake of Livestock and poultry meats and oil and the improvement of LARS was significant in this study. It provides evidence for medical staff to make up effective interventions of moderating diet to promote the relief of LARS during the first 6 months after sphincter-saving surgery.

Abstract Background Abnormal expression of long non-coding RNA (lncRNA) FTX (five prime to Xist), which is involved in X chromosome inactivation, has been reported in various tumors. However, the effect of FTX on the development of pancreatic cancer (PC) has not been elucidated. The purpose of this study was to explore the possible molecular mechanism of FTX in PC. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the expression levels of FTX and miR-513b-5p in PC cell lines. Proliferation and apoptosis of PC cells were determined by CCK-8, Edu assay, and flow cytometry. Invasion and migration ability of PC cells were detected by Transwell assay and scratch test. Bioinformatics analysis, luciferase reporter gene assay, and RNA immunoprecipitation (RIP) assay were used to verify the direct binding between FTX and miR-513b-5p. The xenotransplantation mouse model was established to explore the effect of FTX and miR-513b-5p on the PC tumor growth in vivo. Results The expression levels of FTX were increased in PC cell lines, and silencing of FTX remarkably suppressed the invasion ability and cell viability. Besides, FTX could bind to miR-513b-5p as a competitive endogenous RNA, thus promoting the invasion and proliferation ability of PC cells. Moreover, knockdown of FTX inhibited the tumor growth and increased the expression levels of miR-513b-5p and apoptosis-related proteins in vivo. Conclusions FTX could directly combine with miR-513b-5p as a competitive endogenous RNA, thus promoting the occurrence and development of PC in vitro and in vivo.

Atogepant is a potent, selective, oral calcitonin gene–related peptide (CGRP) receptor antagonist in development for migraine prevention. The chemical structure of atogepant is distinct from previous CGRP receptor antagonists, which were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report the safety, tolerability, and pharmacokinetics (PKs) of a once‐daily supratherapeutic dose (170 mg) of atogepant for 28 days from a randomized, double‐blind, placebo‐controlled phase I trial in healthy participants. Overall safety, hepatic safety, and plasma PK parameters were evaluated. Thirty‐four participants aged 23–55 years enrolled; 28 (82.4%) completed the study in accordance with the protocol. Multiple doses of 170 mg atogepant for 28 consecutive days were generally well‐tolerated. All adverse events (AEs; reported in 87.0% of the atogepant group; 72.7%, placebo) were mild in severity except one serious AE of subarachnoid hemorrhage due to a bicycle accident and not considered related to treatment. There were two discontinuations due to AEs, both with atogepant, one considered possibly related to treatment. Over 28 days of treatment, no participant receiving atogepant had an ALT elevation above 1.5 × upper limit of normal. Change from baseline in serum ALT levels was not different between atogepant and placebo. Atogepant is rapidly absorbed (median time to maximum plasma concentration, ~ 2 hours) with an apparent terminal half‐life of ~ 11 hours, and no evidence of accumulation after once‐daily dosing. Overall, atogepant at a high oral dose is safe and well‐tolerated in healthy participants with no clinically meaningful elevations in ALT.

Qin et al. show the involvement of Kindlin-2 in osteocyte mechanotransduction. They show Kindlin-2 mediates skeletal responses to mechanical stimulation through Smad 2/3 mediated inhibition of Sclerostin.

Arginine methyltransferases (PRMTs) are involved in the regulation of various physiological and pathological conditions. Using proteomics, the authors here profile the methylation substrates of PRMTs 4, 5 and 7 and characterize the roles of these enzymes in cancer-associated splicing regulation.

Abstract Background Coronary hyper-intense plaque (CHIP) detected on T1-weighted cardiovascular magnetic resonance (CMR) has been shown to associate with vulnerable plaque features and worse outcomes in low- and intermediate-risk populations. However, the prevalence of CHIP and its clinical significance in the higher-risk acute coronary syndrome (ACS) population have not been systematically studied. This study aims to assess the relationship between CHIP and ACS clinical severity using intracoronary optical coherence tomography (OCT) as the reference. Methods A total of 62 patients with known or suspected coronary artery disease were prospectively enrolled including a clinically diagnosed ACS group (n = 50) and a control group with stable angina pectoris (n = 12). The ACS group consisted of consecutive patients including unstable angina pectoris (n = 27), non-ST-segment-elevation myocardial infarction (non-STEMI) (n = 8), and ST-segment-elevation myocardial infarction (STEMI) (n = 15), respectively. All patients underwent non-contrast coronary CMR to determine the plaque-to-myocardium signal intensity ratio (PMR). Results Among the four groups of patients, a progressive increase in the prevalence of CHIPs (stable angina, 8%; unstable angina, 26%; non-STEMI, 38%; STEMI, 67%; p = 0.009), and PMR values (stable angina, 1.1; unstable angina, 1.2; non-STEMI, 1.3; STEMI, 1.6; median values, P = 0.004) were observed. Thrombus (7/8, 88% vs. 4/22, 18%, p = 0.001) and plaque rupture (5/8, 63% vs. 2/22, 9%, p = 0.007) were significantly more prevalent in CHIPs than in plaques without hyper-intensity. Elevated PMR was associated with high-risk plaque features including plaque rupture, thrombus, and intimal vasculature. A positive correlation was observed between PMR and the number of high-risk plaque features identified by OCT (r = 0.44, p = 0.015). Conclusions The prevalence of CHIPs and PMR are positively associated with the disease severity and high-risk plaque morphology in ACS.

Abstract The F-box genes, which form one of the largest gene families in plants, are vital for plant growth, development and stress response. However, F-box gene family in Sedum alfredii remains unknown. Comprehensive studies addressing their function responding to cadmium stress is still limited. In the present study, 193 members of the F-box gene (SaFbox) family were identified, which were classified into nine subfamilies. Most of the SaFboxs had highly conserved domain and motif. Various functionally related cis-elements involved in plant growth regulation, stress and hormone responses were located in the upstream regions of SaFbox genes. RNA-sequencing and co-expression network analysis revealed that the identified SaFbox genes would be involved in Cd stress. Expression analysis of 16 hub genes confirmed their transcription level in different tissues. Four hub genes (SaFbox40, SaFbox51, SaFbox136 and SaFbox170) were heterologously expressed in a Cd-sensitive yeast cell to assess their effects on Cd tolerance. The transgenic yeast cells carrying SaFbox40, SaFbox51, SaFbox136, or SaFbox170 were more sensitive and accumulated more cadmium under Cd stress than empty vector transformed control cells. Our results performed a comprehensive analysis of Fboxs in S. alfredii and identified their potential roles in Cd stress response.

Transitional shale gas, rich in resources, is expected to be a practical contributor to the increase in shale gas reserves and production in China. Its exploration prospect has been demonstrated by several wells in the Daning-Jixian block on the eastern margin of the Ordos Basin. In this paper, the Lower Permian Shanxi Formation (P1s) and Taiyuan Formation (P1t) in the eastern margin of Ordos Basin were compared for organic geochemical parameters, revealing that the overflow fan + lagoon combination (OLC) of the third sub-member of the second member of Shanxi Formation (P1s23) and the marine + lagoon combination (MLC) of the first member of Taiyuan Formation (P1t1) are the most favorable shale gas intervals. The two intervals were comparatively analyzed with respect to mineral composition, brittleness, caprocks, and preservation conditions. It is found that the OLC of P1s23 has a similar porosity to and much lower permeability than the MLC of P1t1 (or MLC1) and a BET surface area of 10–15 m2/g, which is smaller than the MLC1 (15–20 m2/g). Moreover, OLC has a brittle mineral content equivalent to MLC1 but a brittleness index of 33.73–62.36 (avg. 49.86), smaller than MLC1 (53.34–58.27, or avg. 55.85). OLC contains sandstones at both the roof and floor, with a higher permeability than shale in the interval, which cannot serve as good physical seals. In contrast, MLC1 contains limestones with lower permeability at the roof and floor, which, together with the overlying coal seams, have hydrocarbon generation capacity and can physically seal the MLC1 shale but also fill it with hydrocarbons, making MLC1 have higher gas content and superior for shale gas exploration than the OLC shale. Due to the multi-lithologies developed in transitional facies, besides the organic matter enrichment, and reservoir characteristics, it is necessary to find a suitable lithological combination to ensure the gas in shale can be better preserved and retained.

Individual interviews were conducted with a total of 66 participants from five groups between May and November 2020: left-behind children, parents, teachers, principals, and community workers. The left-behind children group included 16 primary and secondary school students aged 10–16. Themes in the interviews’ data were identified based on the Grounded Theory. Left-behind children’s social maladjustment manifested as: (1) depression and loneliness; and (2) poor academic performance. Left-behind children’s positive social adjustment manifested as: (1) using adaptive coping strategies; and (2) life skills and independence. Left-behind children’s social adjustment is a dynamic process and has both positive and negative aspects.

Set Intersection Cardinality (SI-CA) computes the intersection cardinality of two parties’ sets, which has many important and practical applications such as data mining and data analysis. However, in the face of big data sets, it is difficult for two parties to execute the SI-CA protocol repeatedly. In order to reduce the execution pressure, a Private Set Intersection Cardinality (PSI-CA) protocol based on a quantum homomorphic encryption scheme for the Toffoli gate is proposed. Two parties encode their private sets into two quantum sequences and encrypt their sequences by way of a quantum homomorphic encryption scheme. After receiving the encrypted results, the semi-honest third party (TP) can determine the equality of two quantum sequences with the Toffoli gate and decrypted keys. The simulation of the quantum homomorphic encryption scheme for the Toffoli gate on two quantum bits is given by the IBM Quantum Experience platform. The simulation results show that the scheme can also realize the corresponding function on two quantum sequences.

In order to meet the urgent need for high temperature piezoelectric materials with a Curie temperature over 400 °C, the Mn/Nb co-doped strategy has been proposed to improve the weak piezoelectric performance of the Aurivillius-type Na0.5Bi4.5Ti4O15 (NBT) high temperature piezoelectric ceramics. In this paper, the crystal structure, electrical properties, and thermal stability of the B-site Mn/Nb co-doped Na0.5Bi4.5Ti4-x(Mn1/3Nb2/3)xO15 (NBT-100x) ceramics were systematically investigated by the conventional solid-state reaction method. The crystal structural analysis results indicate that the NBT-100x ceramics have typical bismuth oxide layer type phase structure and high anisotropic plate-like morphology. The lattice parameters and the grain sizes increase with the B-site Mn/Nb co-doped content. The electrical properties were significantly improved by Mn/Nb co-doped modifications. The maximum of the piezoelectric coefficient d33 was found to be 29 pC/N for the NBT-2 ceramics, nearly twice that of the unmodified NBT ceramics. The highest values of the planar electromechanical coupling factor kp and thickness electromechanical coupling factor kt were also obtained for the NBT-2 ceramics, at 5.4% and 31.2%, respectively. The dielectric spectroscopy showed that the Curie temperature Tc of the Mn/Nb co-doped NBT-100x ceramics is slightly higher than that of unmodified NBT ceramics (646 °C). The DC resistivity of the NBT-2 ceramics is higher than 106 Ω∙cm at 500 °C. All the results together with the good thermal stability demonstrated the Mn/Nb co-doped ceramics as an effective method to improve the NBT based piezoelectric ceramics and the potential candidates of the Mn/Nb co-doped NBT-100x ceramics for high temperature piezoelectric applications.

Most breast cancer heritability is unexplained. We hypothesized that analysis of unrelated familial cases in a GWAS context could enable the identification of novel susceptibility loci. In order to examine the association of a haplotype with breast cancer risk, we performed a genome-wide haplotype association study using a sliding window analysis of window sizes 1–25 SNPs in 650 familial invasive breast cancer cases and 5021 controls. We identified five novel risk loci on 9p24.3 (OR 3.4; p 4.9 × 10−11), 11q22.3 (OR 2.4; p 5.2 × 10−9), 15q11.2 (OR 3.6; p 2.3 × 10−8), 16q24.1 (OR 3; p 3 × 10−8) and Xq21.31 (OR 3.3; p 1.7 × 10−8) and confirmed three well-known loci on 10q25.13, 11q13.3, and 16q12.1. In total, 1593 significant risk haplotypes and 39 risk SNPs were distributed on the eight loci. In comparison with unselected breast cancer cases from a previous study, the OR was increased in the familial analysis in all eight loci. Analyzing familial cancer cases and controls enabled the identification of novel breast cancer susceptibility loci.

Carbon-encapsulated transition metal catalysts have caught the interest of researchers in the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) due to their distinctive architectures and highly tunable electronic structures. In this work, we synthesized N-doped carbon encapsulated with CoNi nanoalloy particles (CoNi@NC) as the electrocatalysts. The metal-organic skeleton ZIF-67 nanocubes were first synthesized, and then Ni2+ ions were inserted to generate CoNi-ZIF precursors by a simple ion-exchange route, which was followed by pyrolysis and with urea for the introduction of nitrogen (N) at a low temperature to synthesize CoNi@NC composites. The results reveal that ZIF-67 pyrolysis can dope more N atoms in the carbon skeleton and that the pyrolysis temperature influences the ORR and OER performances. The sample prepared by CoNi@NC pyrolysis at 650 °C has a high N content (9.70%) and a large specific surface area (167 m2 g−1), with a positive ORR onset potential (Eonset) of 0.89 V vs. RHE and half-wave potential (E1/2) of 0.81 V vs. RHE in 0.1 M KOH, and the overpotential of the OER measured in 1 M KOH was only 286 mV at 10 mA cm−2. The highly efficient bifunctional ORR/OER electrocatalysts synthesized by this method can offer some insights into the design and synthesis of complex metal-organic frameworks (MOFs) hybrid structures and their derivatives as functional materials in energy storage.

Abstract GaAs nanostructures have attracted more and more attention due to its excellent properties such as increasing photon absorption. The fabrication process on GaAs substrate was rarely reported, and most of the preparation processes are complex. Here, we report a black GaAs fabrication process using a simple inductively coupled plasma etching process, with no extra lithography process. The fabricated sample has a low reflectance value, close to zero. Besides, the black GaAs also displayed hydrophobic property, with a water contact angle of 125°. This kind of black GaAs etching process could be added to the fabrication workflow of photodetectors and solar cell devices to further improve their characteristics.

Chilled duck meat is a popularly consumed meat in China but easily perishes at room/low temperature. Kojic acid is usually used as an antimicrobial. This study investigated the sensory scores, total bacteria number, and total volatile base nitrogen (TVB-N) value of chilled duck meat under kojic acid treatment during storage. The results presented that kojic acid suppressed the growth of spoilage bacteria and prolonged the shelf-life of chilled duck meat by at least two days. In further investigation, the bacterial community composition was explored through high-throughput sequencing. Pseudomonas spp. were the predominant spoilage bacteria after 6-day storage and were significantly suppressed by kojic acid. Besides, Brochothrix showed drug resistance and became the dominant bacteria in the kojic acid treated sample after 6-day storage. In conclusion, kojic acid maintained the sensorial, chemical, and microbial quality of duck meat stored at low temperatures. Meanwhile, kojic acid enriched the bacteria composition and showed strong antimicrobial activity against Pseudomonas spp.