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IntroductionThe rapid development of the farming industry has increased the amount of manure produced by livestock and poultry, causing increasingly prominent environmental pollution problems. In recent years, due to the increase in conventional bedding material costs, an increasing number of farmers choose to use harmless recycled manure as bedding. Manure bedding treatment of farms can not only solve the problem of manure pollution, but also resource utilization of manure and cost savings.MethodsThis study compared the effects of five microbial agents (Microbial agents A, B, C, E, F) on buffalo manure bedding treatment by testing the temperature, moisture content, pH, microbial bacteria distribution of buffalo manure ectopic fermentation, and screened the lowest cost and most effective agent. The changes of microbial bacteria distribution in different periods of bedding treatment were also detected.ResultsAgent A was eliminated because of poor fermentation effect and low fermentation temperature, which could not achieve the effect of harmless treatment. The other four agents of bacteria achieved a harmless effect, but the bedding treatment effect of agent F was significantly better than agent E, B, and C. In terms of the cost of agents: the cost of agent F required for fermenting 100m³ buffalo manure was the lowest, 1000yuan, followed by E (1200yuan), C (1750yuan), and B (1980yuan). In the process of ectopic fermentation bedding treatment of buffalo manure, Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Chloroflexi were the major bacteria used. The process was divided into three periods; the heating period - high temperature period - cooling period, the high temperature period could reach more than 75°C, and a large number of pathogenic bacteria and harmful bacteria, and other miscellaneous bacteria in the pile were degraded, their species diversity was reduced, and the structure of bacterial flora had significant differences in different treatment periods. In conclusion, this study has provided a guide for the resource utilization of manure in cattle farms and the reduction of manure pollution to the environment.

BackgroundPost-operative delirium (POD), a common post-operative complication that affects up to 73. 5% of surgical patients, could prolong hospital stays, triple mortality rates, cause long-term cognitive decline and dementia, and boost medical expenses. However, the underlying mechanisms, especially the circuit mechanisms of POD remain largely unclear. Previous studies demonstrated that cannabis use might cause delirium-like behavior through the endocannabinoid system (eCBs), a widely distributed retrograde presynaptic neuromodulator system. We also found that the prelimbic (PrL) and intralimbic (IL) prefrontal cortex, a crucial hub for cognition and emotion, was involved in the eCBs-associated general anesthesia recovery.ObjectivesThe present study aimed to investigate the role of eCBs in POD development, and further clarify its neuronal specificity and circuit specificity attributed to POD.MethodsAccording to a previous study, 2 h of 1.4% isoflurane anesthesia and simple laparotomy were conducted to establish the POD model in C57/BL6 mice aged 8–12 weeks. A battery of behavioral tests, including the buried food, open field, and Y maze tests, were performed at 24 h before anesthesia and surgery (AS) and 6 and 9 h after AS. The behavioral results were calculated as a composite Z score for the POD assessment. To explore the dynamics of eCBs and their effect on POD regulation, an endocannabinoid (eCB) sensor was microinjected into the PrL, and the antagonists (AM281 and hemopressin) and agonist (nabilone) of type 1 cannabinoid receptor (CB1R), were administered systemically or locally (into PrL). Chemogenetics, combined Cre-loxP and Flp-FRT system, were employed in mutant mice for neuronal specificity and circuit specificity observation.ResultsAfter AS, the composite Z score significantly increased at 6 and 9 but not at 24 h, whereas blockade of CB1R systemically and intra-PrL could specifically decrease the composite Z score at 6 and 9 h after AS. Results of fiber photometry further confirmed that the activity of eCB in the PrL was enhanced by AS, especially in the Y maze test at 6 h post-operatively. Moreover, the activation of glutamatergic neurons in the PrL could reduce the composite Z score, which could be significantly reversed by exogenous cannabinoid (nabilone) at 6 and 9 h post-operatively. However, activation of GABAergic neurons only decreased composite Z score at 9 h post-operatively, with no response to nabilone application. Further study revealed the glutamatergic projection from mediodorsal thalamus (MD) to PrL glutamatergic neurons, but not hippocampus (HIP)-PrL circuit, was in charge of the effect of eCBs on POD.ConclusionOur study firstly demonstrated the involvement of eCBs in the POD pathogenesis and further revealed that the eCBs may regulate POD through the specific MDglu-PrLglu circuit. These findings not only partly revealed the molecular and circuit mechanisms of POD, but also provided an applicable candidate for the clinical prevention and treatment of POD.

Ammonia has been reported to have a variety of toxicity to aquatic animals, farm animals and humans. However, its potential toxicity on the intestines remains unknown. L-selenomethionine is one of the important organic selenium sources. However, the mitigating effect of L-selenomethionine on ammonia exposure toxicity is still lacking. Therefore, in this study, the mechanism of toxic action of ammonia on intestinal tract and the detoxification effect of L-selenomethionine were examined. We evaluated the intestinal toxicity of ammonia and the alleviating effect of L-selenomethionine in an in vivo model, and then verified it in vitro model by a variety of cutting-edge experimental techniques. Our results showed that ammonia exposure causes oxidative stress, necroptosis, Th1/Th2 imbalance and inflammation in the intestinal tissue and the intestinal cells, and L-selenomethionine had a significant mitigation effect on the changes of these indexes induced by ammonia. In conclusion, ammonia exposure caused oxidative stress and Th1/Th2 imbalance in the porcine small intestine and IPEC-J2 cells, and that excessive ROS accumulation-mediated necroptosis targeted inflammatory responses, resulting in the destruction of tight connections of intestinal cells, thereby causing intestinal barrier dysfunction. L-selenomethionine could effectively reduce the intestinal injury caused by ammonia exposure and antagonize the toxic effect of ammonia.

BackgroundMobile phone–based digital interventions have been shown to be a promising strategy for HIV prevention among men who have sex with men (MSM). ObjectiveThis study aimed to evaluate the cost-effectiveness of a mobile phone–based digital intervention for HIV prevention among MSM in China from the perspective of a public health provider. MethodsThe cost-effectiveness of the mobile phone–based digital intervention was estimated for a hypothetical cohort of 10,000 HIV-negative MSM who were followed for 1 year. A model was developed with China-specific data to project the clinical impact and cost-effectiveness of two mobile phone–based digital strategies for HIV prevention among MSM. The intervention group received an integrated behavioral intervention that included 1) individualized HIV infection risk assessment, 2) recommendation of centers testing for HIV and other STIs, 3) free online order of condoms and HIV and syphilis self-test kits and 4) educational materials about HIV/AIDS. The control group was only given educational materials about HIV/AIDS. Outcomes of interest were the number of HIV infections among MSM averted by the intervention, intervention costs, cost per HIV infection averted by the mobile phone–based digital intervention, and quality-adjusted life-years (QALYs). Univariate and multivariate sensitivity analyses were also conducted to examine the robustness of the results. ResultsIt is estimated that the intervention can prevent 48 MSM from becoming infected with HIV and can save 480 QALYs. The cost of preventing 1 case of HIV infection was US $2599.87, and the cost-utility ratio was less than 0. Sensitivity analysis showed that the cost-effectiveness of the mobile phone–based digital intervention was mainly impacted by the average number of sexual behaviors with each sexual partner. Additionally, the higher the HIV prevalence among MSM, the greater the benefit of the intervention. ConclusionsMobile phone–based digital interventions are a cost-effective HIV-prevention strategy for MSM and could be considered for promotion and application among high-risk MSM subgroups.

Early adversity can cause malfunction of the visual system in adulthood. Adult female but not male mice undergoing early chronic mild stress (ECMS) maintain ocular dominance (OD) plasticity after the critical period. How early stressful experiences have a long-term impact on it is largely unknown. Here, we observed a wide distribution of corticotropin-releasing factor (CRF)-positive neurons, which mainly colocalized with a subpopulation of GABAergic interneurons in the mouse primary visual cortex (V1). Optogenetic activation of CRF-positive neurons transfected with AAV-ChR2 evoked inhibitory currents in nearby pyramidal cells. ECMS induced a reduction in the expression of CRF mRNA in adult mouse V1. Chemogenetic activation of V1 CRF neurons impaired OD plasticity in adult ECMS females. We further showed that local administration of the corticotropin releasing factor receptor 1 (CRFR1) antagonist via an osmotic minipump into the visual cortex mimicked OD plasticity in adult ECMS females. Whole-cell recording in layer 2/3 pyramidal neurons revealed that the CRFR1 antagonist reduced the short-term depression (STD) of evoked inhibitory postsynaptic current (IPSC) in females but not in males. Likewise, CRF agonists have the opposite effect. In summary, our findings indicate that the local CRF-CRFR1 system within V1 may mediate the long-term and sex-dependent effect of early stress experiences on visual plasticity and provide a target for the prevention of visual deficits in adults with a history of early-life adversity.

The MADS-box gene family plays a crucial role in multiple developmental processes of plants, especially in floral organ specification and the regulation of fruit development and ripening. Juglans mandshurica is a precious fruit material whose quality and yield are determined by floral organ development. The molecular mechanism of J. mandshurica female and male flower development depending on MADS-box genes remains unclear. In our study, 67 JmMADS genes were identified and unevenly distributed on 15 of 16 J. mandshurica chromosomes. These genes were divided into two types [type I (Mα, Mγ, Mδ) and type II (MIKC)]. The gene structure and motif analyses showed that most genes belonging to the same type had similar gene structures and conserved motifs. The analysis of syntenic relationships showed that MADS-box genes in J. mandshurica, J. sigillata, and J. regia exhibited the highest homology and great collinearity. Analysis of cis-acting elements showed that JmMADS gene promoter regions contained light, stress and hormone response cis-acting elements. The gene expression patterns demonstrated that 30 and 26 JmMADS genes were specifically expressed in the female and male flowers, respectively. In addition, 12 selected genes common to J. mandshurica female and male flowers were significantly upregulated at the mature stage and were used to validate the reliability of the transcriptome data using quantitative real-time PCR. This comprehensive and systematic analysis of J. mandshurica MADS-box genes lays a foundation for future studies on MADS-box gene family functions.

Recycling of agricultural waste as adsorbents for pollutant removal realizes “Waste to Resource”. This study utilized an abundant fruit waste material, watermelon rind (WR), to remove Cd(II) from aqueous solutions (Cd(II) solution in distilled deionized water) in a batch mode, and the underlying adsorption mechanism was deciphered by complementary methods. The Cd(II) adsorption process rapidly reached equilibrium in 60 min, with 90% of adsorption finished in 10 min (50 mg/L Cd(II), 0.5 g/L WR). The maximum Cd(II) adsorption capacity of WR was 102.0 ± 0.1 mg/g at pH 7.0 (25–500 mg/L Cd(II), 1.0 g/L WR), and the Dubinin-Radushkevich isotherm and pseudo-second-order kinetic models provided the best description to the adsorption process. Spectroscopic analysis using Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) showed hydroxyl, carboxyl, ether, and amine groups as the binding sites, probably via complexation. Physicochemical analysis such as zeta potential measurement and scanning electron microscopy coupled with electron dispersive X-ray spectroscopy (SEM-EDS) revealed the occurrence of electrostatic interaction and microprecipitation. Moreover, ion exchange of Cd(II) with Mg2+and Ca2+ bound to WR contributed to 83% of the Cd(II) adsorption. The findings indicate the great potential of WR for Cd(II) removal from wastewater. The mechanism elucidation uncovered the interactions between Cd(II) and the WR surface, providing insights to the development and optimization of biosorbents derived from agricultural waste.

ObjectiveWe aimed to explore the impact of using virtual reality technology to intervene in and encourage the developmental behavior areas of cognition, imitation, and social interaction in children with autism spectrum disorder.MethodsForty-four children with autism spectrum disorder were divided randomly into an intervention group and a control group, with each group consisting of 22 participants. Incorporating conventional rehabilitation strategies, virtual reality technology was used with the intervention group to conduct rehabilitation training in areas including cognition, imitation, and social interaction. The control group was provided conventional/routine clinical rehabilitation training. The children's cognitive development was evaluated before and 3 months after intervention.ResultsAfter intervention, the developmental abilities of both groups of children in the areas of cognition, imitation, and social interaction were improved over their abilities measured before the intervention (P < 0.05). However, post-intervention score differences between the two groups demonstrated that the intervention group levels were better than the control group levels only in the areas of cognition and social interaction (P < 0.05).ConclusionCombining virtual reality with conventional rehabilitation training improved the cognitive and social development of children with autism spectrum disorder and supported the goal of improving the rehabilitation effect.

Saposhnikovia divaricata is an important economic medicinal plant in eastern Asia. It is the National Grade III Key Protected Wild Medicinal Plants in China. However, little is known about the effects of projected climate change on its adaptability and future distribution. In this study, we simulated the suitable area of S. divaricata under current (1970–2000) and four climate change scenarios (i.e., SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5) in 2050s (2041–2060), 2070s (2061–2080) and 2090s (2081–2100) using maximum entropy model (MaxEnt). The results demonstrated that temperature seasonality (Bio04), precipitation seasonality (Bio15), elevation (Ele), and isothermally (Bio03) were the most important environmental variables determining the distribution of S. divaricata. Under the current climate situation, the suitable areas were mainly located in Northeast China and North China, with a total area of 134.87 × 104km2. The grassland is the largest land use type in the suitable area of S. divaricata. The priority planting region of S. divaricata are located in the southwest of Heilongjiang and the northwest of Jilin Province. The wild tending region is located in the middle east of Inner Mongolia. Under the future climate scenarios, the suitable areas of S. divaricata showed increasing trends. SSP5-8.5 scenario would have the highest area growth, with 43.09 %, 61.15 %, and 62.11 % increase in the three periods (2050s, 2070s, and 2090s). In addition, the high latitude migration of the geometric center of the total suitable area is predicted. Our results could provide a reference for the conservation and sustainable development and utilization of this species in the future.

It is obvious that investigating a text or a poem, regardless of the culture of the period in which the writer or poet lived, is futile. The current study explores the conceptual metaphors formed by culture in the functioning of the autumn word in the works of Russian poetry. The relevance of the work is due to the need for a comprehensive study of those language units that play an essential role in the embodiment of the author’s intention. At the same time, not all words expressing a temporary meaning have received comprehensive coverage in the scientific literature. Among these, lexemes are the word “autumn”. The purpose of the study is to analyze the functioning of the “autumn” lexeme in poetic works of the XX-XXI centuries. Considerable attention is paid to the realization of the creative potential of the temporal lexeme. The material for the study was poetry texts extracted from the “National Corpus of the Russian Language”.

Abstract Background Restenosis after angioplasty is a major challenge for the treatment of coronary artery diseases. Facilitation of vascular smooth muscle cell (VSMC) apoptosis may be an attractive approach to decrease the incidence of restenosis. We synthesized a 16-amino acid mitofusin-2 (Mfn-2) gene related peptide (MRSP) based on the sequence of the p21ras signature motif, the smallest functional sequence of the Mfn-2 gene with proapoptotic properties in VSMC. We investigated whether MRSP enhanced apoptotic activities to inhibit VSMC accumulation and neointimal hyperplasia in rats with carotid balloon injury. Methods VSMCs were treated with different concentrations of MRSP, the PI3K agonist 740 Y-P and the inhibitor LY294002. Cell apoptosis and related pathway molecules were assessed. MRSP was also given to rats with carotid artery balloon injury. Neointimal hyperplasia and cell apoptotic pathways were detected. Results In vitro experiments revealed that MRSP treatment significantly increased VSMC apoptosis and induced increases in procaspase-9 cleavage, caspase-3 activation, cytochrome c release from mitochondria to the cytoplasm and the Bax/Bcl-2 ratio but not caspase-8 expression, indicating that the mitochondrial apoptotic cascade was activated by MRSP, which might be attributed to suppression of the PI3K/Akt signaling pathway. We further found that the PI3K agonist 740 Y-P prevented and that the inhibitor LY294002 strengthened the proapoptotic effects of MRSP. MRSP strongly inhibited neointimal hyperplasia and VSMC accumulation, but increased VSMC apoptosis in the vascular wall after balloon injury. Moreover, MRSP substantially enhanced Bax and cleaved caspase-3 expression and decreased Bcl-2 levels in intima, accompanied by decreased levels of phosphorylated Akt and PI3K in vivo. Conclusions Taken together, the present study showed that MRSP treatment results in a strong proapoptotic effect by activating the mitochondrial apoptotic cascade through suppression of the PI3K/Akt pathway.

In order to enhance the aqueous solubility and stability of etoposide preparation,the central composite design-response surface method was used to optimize the prescription technology of etoposide nano-mixed micelles (ETP mPEG-PLA/P123).Based on the results of single factor test,central composite design-response surface method of three factors and five levels was carried out to optimize the prescription technology with drug dosage,the mass ratio of mPEG-PLA and hydration volume as independent variables,and the entrapment efficiency,drug loading and particle size as dependent variables.The critical micelle concentration (CMC) was determined by fluorescence probe method,and the physicochemical properties and release behavior of the prepared micelle preparations were evaluated.The results showed that the optimal prescription of ETP mPEG-PLA/P123 micelle preparation was that mPEG-PLA∶P123=38∶62,the drug dosage was 5 mg,and the hydration volume was 6 mL.After optimization,the entrapment efficiency and drug loading were 874% and 419%,the particle size was 1156 nm,PDI was 0216,and Zeta potential was -163 mV.The CMC value was 17×10-3 g/L,so mPEG-PLA/P123 micelles had high stability.In vitro release experiments,etoposide could be released from micelles slowly and continuously,up to 80% within 48 h.The optimized ETP mPEG-PLA/P123 nano-mixed micelles were able to enormously improve the aqueous solubility of etoposide,and the micelle preparation had good stability and a certain slow-release effect.The results of this study could provide theoretical guidance for further broadening the range of application of new etoposide preparations.

Abstract Background Tissue-engineered bone grafts (TEBGs) that undergo vascularization and neurotization evolve into functioning bone tissue. Previously, we verified that implanting sensory nerve tracts into TEBGs promoted osteogenesis. However, the precise mechanisms and interaction between seed cells were not explored. In this study, we hypothesized that neurotization may influence the osteogenesis of TEBGs through vascularization. Methods We cultured rat Schwann cells (SCs), aortic endothelial cells (AECs), and bone marrow-derived mesenchymal stem cells (BM-MSCs) and then obtained BM-MSC-derived induced endothelial cells (IECs) and induced osteoblasts (IOBs). IECs and AECs were cultured in an SC-conditioned medium (SC-CM) to assess proliferation, migration, capillary-like tube formation, and angiogenesis, and the vascular endothelial growth factor (VEGF) levels in the supernatants were detected. We established an indirect coculture model to detect the expression of nestin and VEGF receptors in IECs and tissue inhibitor of metalloproteinase (TIMP)-2 in SCs. Then, SCs, IECs, and IOBs were labeled and loaded into a β-tricalcium phosphate scaffold to induce prevascularization, and the scaffold was implanted into a 6-mm-long defect of rat femurs. Three groups were set up according to the loaded cells: I, SCs, and IECs (coculture for 3 days) plus IOBs; II, IECs (culture for 3 days) plus IOBs; III, IOBs. Nestin and TIMP-2 expression and osteogenesis of TEBGs were evaluated at 12 weeks post-implantation through histological and radiological assessments. Results We found that SC-CM promoted IEC proliferation, migration, capillary-like tube formation, and angiogenesis, but no similar effects were observed for AECs. IECs expressed nestin extensively, while AECs barely expressed nestin, and SC-CM promoted the VEGF secretion of IECs. In the coculture model, SCs promoted nestin and VEGF receptor expression in IECs, and IECs inhibited TIMP-2 expression in SCs. The promotion of prevascularized TEBGs by SCs and IECs in group I augmented new bone formation at 6 and 12 weeks. Nestin expression was higher in group I than in the other groups, while TIMP-2 expression was lower at 12 weeks. Conclusions This study demonstrated that SCs can promote TEBG osteogenesis via IECs and further revealed the related specific characteristics of IECs, providing preliminary cytological evidence for neurotization of TEBGs.

COVID-19 pandemic is a global health risk, but our understanding on the induced durable immunity remains scarce. Here the authors assess antibody responses in 869 convalescent COVID-19 patients to find that specific antibody titers reduce with time, and the RBD-IgG positive rate exceed 70% at 12 month post diagnosis, with male and older patients showing stronger responses.

Ammonia (NH3) is a common air pollutant, which poses a serious threat to farm animals. L-selenomethionine is organic selenium (Se), which can inhibit intracellular ROS generation, block ROS-dependent autophagy, promote mitochondrial energy metabolism, and enhance the body's immunity. Lung, as an important organ of the respiratory system, is highly susceptible to the toxic effects of NH3. However, there were few studies on the mechanism of toxic effects of NH3 on lung tissues. The aim of this study was to investigate the effect of NH3 on the lungs in pigs and the alleviating effect of L-selenomethionine. Twenty-four Large White*Duroc*Min pigs were randomly assigned to 4 groups: control group, NH3 group, Se group, and NH3 +Se group. The results showed that exposure to NH3 caused damage and inflammation in lung tissues and significantly increased blood NH3 concentration. NH3 induced changes of oxidative stress indexes (GSH, GSH-Px, SOD, MDA, Keap1, Nrf2, and HO-1) and expressions of energy metabolism related genes (HK1, HK2, PFK, PK, LDHA, and HIF-1α). Ultrastructure showed that mitochondrial damage and autophagosome increased significantly, and the expression levels of autophagy related genes (Beclin1, ATG5, ATG7, ATG10, and p62) changed. However, the addition of L-selenomethionine alleviated the above changes, but there was still a significant difference compared with the control group (P

Sea fog significantly impacts harbor operations, at times even causing navigation to cease. This study examines two harbors in the north of the South China Sea, analyzing the feasibility of increasing each harbor’s sea fog early warning capability to 6 h in advance. Although the harbors are separated by only about 100 km, analysis of their backward trajectories reveals differences in the incoming flow and sea fog types. Concerning the types, at Xuwen harbor, warm advection fog represents 49.56% of the cases, cold advection representing 48.03%. At Zhanjiang harbor, 37.06% are warm advection fog, with 58.33% cold advection fog cases. We propose different monitoring and early warning schemes for the harbors. For Xuwen, we suggest eight visibility lidars located on the north and south sides of Qiongzhou Strait (two on the north, six on the south). Here, such a setup would give warning probabilities of sea fog of 87.50, 66.23, and 49.78% for advance times of 2, 3, and 4 h. For Zhanjiang, we suggest two visibility lidars and four buoys at the east side of the harbor. The corresponding warning probabilities are 83.77, 64.47, and 47.15% for the same advance times. For 5–6 h in advance, the early warning probabilities of both harbors drop quickly. We also suggest a flow chart for the early warning and monitoring scheme at each harbor.

Light is not only a very important source of energy for the normal growth and development of plants, but also a regulator of many development and metabolic processes. The mechanism of plant growth and development under low light conditions is an important scientific question. With the promulgation of the law to stop natural forest cutting, understory regeneration is an important method for artificial forest afforestation. Here, the growth and physiological indexes of Juglans mandshurica, an important hardwood species in Northeast China, were measured under different shade treatments. In addition, transcriptome and metabolome were compared to analyze the molecular mechanism of shade tolerance in J. mandshurica. The results showed that the seedling height of the shade treatment group was significantly higher than that of the control group, and the 50% light (L50) treatment was the highest. Compared with the control group, the contents of gibberellin, abscisic acid, brassinolide, chlorophyll a, and chlorophyll b in all shade treatments were significantly higher. However, the net photosynthetic rate and water use efficiency decreased with increasing shade. Furthermore, the transcriptome identified thousands of differentially expressed genes in three samples. Using enrichment analysis, we found that most of the differentially expressed genes were enriched in photosynthesis, plant hormone signal transduction and chlorophyll synthesis pathways, and the expression levels of many genes encoding transcription factors were also changed. In addition, analysis of differentially accumulated metabolites showed that a total of 470 differential metabolites were identified, and flavonoids were the major differential metabolites of J. mandshurica under light stress. These results improved our understanding of the molecular mechanism and metabolite accumulation under light stress in J. mandshurica.

Bipolar disorder (BD) is associated with a high risk of suicide. We used proton magnetic resonance spectroscopy (1H-MRS) to detect biochemical metabolite ratios in the bilateral prefrontal white matter (PWM) and hippocampus in 32 BD patients with suicidal ideation (SI) and 18 BD patients without SI, identified potential brain biochemical differences and used abnormal metabolite ratios to predict the severity of suicide risk based on the support vector machine (SVM) algorithm. Furthermore, we analyzed the correlations between biochemical metabolites and clinical variables in BD patients with SI. There were three main findings: (1) the highest classification accuracy of 88% and an area under the curve of 0.9 were achieved in distinguishing BD patients with and without SI, with N-acetyl aspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr values in the bilateral PWM, NAA/Cr and choline (Cho)/Cr values in the left hippocampus, and Cho/Cr values in the right hippocampus being the features contributing the most; (2) the above seven features could be used to predict Self-rating Idea of Suicide Scale scores (r = 0.4261, p = 0.0302); and (3) the level of neuronal function in the left hippocampus may be related to the duration of illness, the level of membrane phospholipid catabolism in the left hippocampus may be related to the severity of depression, and the level of inositol metabolism in the left PWM may be related to the age of onset in BD patients with SI. Our results showed that the combination of multiple brain biochemical metabolites could better predict the risk and severity of suicide in patients with BD and that there was a significant correlation between biochemical metabolic values and clinical variables in BD patients with SI.

ObjectiveThis study assessed the real-world application, effectiveness, and safety of olaparib and niraparib as maintenance therapies in patients with platinum-sensitive recurrent ovarian cancer (PSROC) in China and investigated clinical factors associated with prolonged benefits of poly ADP-ribose polymerase (PARP) inhibitors to help guide clinician treatment-decision making in daily practice.MethodsThis real-world single-center retrospective cohort study was conducted at the Shandong Cancer Hospital and Institute. Archival data of consecutive patients diagnosed with PSROC who achieved a complete response (CR) or partial response (PR) after the last platinum-based chemotherapy and treated with olaparib or niraparib as maintenance therapy from August 2018 to September 2021 were collected.ResultsOverall, 106 women were included in the cohort. Seventy-two (68%) patients were treated with olaparib, while 34 (32%) received niraparib; 99.1% of the patients were diagnosed with high-grade serous carcinoma, and 73.6% had FIGO stages III–IV. Approximately 71.7% of the patients had received PARP inhibitors after the second platinum-based line and 44.3% of the patients achieved a CR in their last platinum-based therapy. The median platinum-free interval (PFI) after the penultimate platinum-based therapy was 10 (95% CI: 10–13.6) months. The median PFS was 21 (95% CI: 13–24.5) months and the median CFI was 22 (95% CI: 16–26.5) months. Consistent with the univariate analysis, the multivariate analysis identified three independent factors associated with prolonged progression-free survival (PFS) and chemotherapy-free interval (CFI): breast cancer susceptibility gene (BRCA) mutant type (p = 0.005 and p = 0.003); PFI ≥12 months (p = 0.01 and p = 0.006); and CR to last platinum-based therapy (p = 0.016 and p = 0.019). It was found that there was no appreciable difference in any grade 3–4 hematological AE between patients who received olaparib and niraparib.ConclusionMaintenance treatment with olaparib and niraparib is effective and well tolerated for PSROC patients in real-world clinical practice. Three clinical factors were identified that predicted prolonged survival under maintenance therapy with PARP inhibitors: BRCA mutant type, PFI ≥12 months, and CR to last platinum-based therapy. These findings should be further confirmed with an appropriately powered analysis in studies with larger sample sizes.

All-solid-state lithium batteries (ASSLBs) have attracted much attention owing to their high safety and energy density compared to conventional organic electrolytes. However, the interfaces between solid-state electrolytes and electrodes retain some knotty problems regarding compatibility. Among the various SSEs investigated in recent years, halide SSEs exhibit relatively good interfacial compatibility. The temperature-dependent interfacial compatibility of halide SSEs in solid-state batteries is investigated by thermal analysis using simultaneous thermogravimetry and differential scanning calorimetry (TG–DSC) and X-ray diffraction (XRD). Halide SSEs, including rock-salt-type Li3InCl6 and anti-perovskite-type Li2OHCl, show good thermal stability with oxides LiCoO2, LiMn2O4, and Li4Ti5O12 up to 320 °C. Moreover, anti-perovskite-type Li2OHCl shows a chemical reactivity with other battery materials (eg., LiFePO4, LiNi0.8Co0.1Mn0.1O2, Si-C, and Li1.3Al0.3Ti1.7(PO4)3) at 320°C, which reaches the melting point of Li2OHCl. It indicated that Li2OHCl has relatively high chemical reactivity after melting. In contrast, rock-salt-type Li3InCl6 shows higher stability and interfacial compatibility. This work delivers insights into the selection of suitable battery materials with good compatibility for ASSLBs.

Diabetic retinopathy (DR) is a common complication and the leading cause of blindness in patients with type 2 diabetes. DR has been shown to be closely correlated with blood glucose levels and the duration of diabetes. However, the onset and progression of DR also display clinical heterogeneity. We applied whole-exome sequencing and RNA-seq approaches to study the gene mutation and transcription profiles in three groups of diabetic patients with extreme clinical phenotypes in DR onset, timing, and disease progression, aiming to identify genetic variants that may play roles in the pathogenesis of DR. We identified 23 putatively pathogenic genes, and ingenuity pathway analysis of these mutated genes reveals their functional association with glucose metabolism, diabetic complications, neural system activity, and dysregulated immune responses. In addition, ten potentially protective genes were also proposed. These findings shed light on the mechanisms underlying the pathogenesis of DR and may provide potential targets for developing new strategies to combat DR.

Ferroelectricity is a property with spontaneous polarization, which is of paramount importance in modern electrooptic applications. Yet, its observations are mostly limited to solids or chiral smectic C liquid crystals with nearly no fluidity. The fluidic ferroelectrics, called ferroelectric nematics, have recently become available by incorporating strong polarity into the apolar liquid crystalline orientational field. Here, we present a rational principle for designing the ferroelectric materials and controlling their phase behaviors. We reveal that, while the apolar nematic order with the second-rank tensor originates from the shape anisotropy in the apolar nematic state, the polarization field serves as an additional mechanism for stabilizing polar nematic orders. Based on a comprehensive set of examinations and machine-learningdriven analyses for about 150 chemically distinct polar rod-shaped molecules, we uncover that the interplay between the shape anisotropy and polarization field gives rise to a diversification of the polar liquid crystal behaviors. The strategy offers much broader design flexibility and may facilitate the development of future polar functional liquid crystals.

ABSTRACT Sweetpotato (Ipomoea batatas) is the eighth most important crop globally. However, the production and quality of sweetpotatoes are threatened by Fusarium diseases that are prevalent around the world. In this study, a Fusarium species that causes root and stem rot in sweetpotatoes was studied. The pathogenic fungus CRI 24-3 was isolated and sequenced using third- and next-generation sequencing techniques and a 49.6 Mb chromosome-level draft genome containing 15,374 putative coding genes were obtained. Molecular phylogenetic analysis showed that CRI 24-3 was an F. solani-melongenae strain within clade 3 of the F. solani species complex (FSSC). CRI 24-3 showed a relatively high number of virulence factors, such as carbohydrate-active enzymes (CAZymes), pathogen-host interaction (PHI) proteins, and terpene synthases (TSs), compared with the number of those identified in other sequenced FSSC members. Comparative genome analysis revealed considerable conservation and unique characteristics between CRI 24-3 and other FSSC species. In conclusion, the findings in the current study provide important genetic information about F. solani-melongenae and should be useful in the exploration of pathogenicity mechanisms and the development of Fusarium disease management strategies. IMPORTANCE Fusarium root and stem rot in sweetpotato are prevalent in the main sweetpotato-growing areas in China, and fungal isolation, morphological characteristics, and molecular phylogenetic analysis of the disease causal agent (F. solani-melongenae isolate CRI 24-3) were systematically studied. The genome sequence of F. solani-melongenae isolates CRI 24-3 was first reported, which should provide a basis for genome assembly of other closely related Fusarium species. Carbohydrate-active enzymes predicted in CRI 24-3 may be important to convert the substantial polysaccharides to sustainable and renewable energy. Moreover, other virulence factors facilitating Fusarium diseases, including effectors and toxic secondary metabolites, are ideal objects for pathogenicity mechanism research and molecular targets for fungicide development. The findings of comparative genome analysis of CRI 24-3 and 15 sequenced members of the F. solani species complex help promote an integral understanding of genomic features and evolutionary relationships in Fusarium.

Triphenyl phosphate (TPhP) is used as a flame retardant that gradually leaks from products into the marine environment and thus may threaten low-trophic-level marine organisms, such as zooplankton. To assess the effect of TPhP on these taxa, we treated the marine rotifer Brachionus plicatilis as a target and examined the changes in key life history parameters and the metabolome after exposure to TPhP at 0.02, 1 and 5 mg/L. Additionally, the rotifer-Phaeocystis population dynamics (a simulation of the prey-predator relationship) were studied under TPhP stress. Our results showed that TPhP at 1 and 5 mg/L reduced the average lifespan and the total offspring number and prolonged the prereproductive time, suggesting damage to survival and fecundity. In the 0.02 mg/L group, no obvious damage occurred in the overall condition of rotifers, but the volume of parental rotifers after the first brood decreased. This implied that rotifers sacrificed somatic growth to reproduction in the initial period of TPhP exposure at the low concentration. All the tested TPhP concentrations altered the rotifer-Phaeocystis population dynamic changes, especially that 1 mg/L TPhP reduced the ability of rotifers to remove this harmful alga, as evidenced by the decrease in the maximum population density of rotifers and the extended time to P. globosa extinction. At the molecular level, metabolomics identified 84 and 206 differentially expressed metabolites, most of which were enriched in glycerophospholipid metabolism, steroid biosynthesis and sphingolipid metabolism. Nile red staining showed a decrease in neutral lipids in rotifers, further indicating a disorder of lipid metabolism induced by TPhP. Moreover, the balance between ROS production and the defense system was disrupted by TPhP, which contributed to its toxicity. This finding will promote the understanding of the ecological risk and mode of action of TPhP in aquatic environments.

Abstract Background Genetic testing of UGT1A1 was used to facilitate the diagnosis of Gilbert syndrome, and analyze the distribution features of pathogenic variants in the Chinese population. Methods DNA was extracted from whole blood samples of patients with unconjugated hyperbilirubinemia, and sequencing of the UGT1A1 gene was performed after PCR amplification. After alignment with reference sequences, the known pathogenic variants were identified, the variant spectrum was analyzed, and the pathogenicity of novel variants was predicted using online mutation prediction tools. Results A total of 117 patients were confirmed with Gilbert syndrome by UGT1A1 genetic diagnosis, where the most common pathogenic variants included promoter A(TA)7TAA insertion and p.Gly71Arg missense variant. Following novel variants were also identified: p.Ala61Gly, p.Tyr67Phe, p.Leu166Alafs*16, p.Arg240Lys, p.Ser306Phe, p.Arg341Gln, and p.Glu424* variants. Conclusions Genetic testing of UGT1A1 in clinical practices could facilitate confirming Gilbert syndrome and performing differential diagnosis. The pathogenic variant spectrum in the Chinese population was similar to other Asian populations. The novel pathogenic variants identified in this study require further investigation.

ObjectiveWith the aging of populations and the high prevalence of stroke, postoperative stroke has become a growing concern. This study aimed to establish a prediction model and assess the risk factors for stroke in elderly patients during the postoperative period.MethodsML (Machine learning) prediction models were applied to elderly patients from the MIMIC (Medical Information Mart for Intensive Care)-III and MIMIC-VI databases. The SMOTENC (synthetic minority oversampling technique for nominal and continuous data) balancing technique and iterative SVD (Singular Value Decomposition) data imputation method were used to address the problem of category imbalance and missing values, respectively. We analyzed the possible predictive factors of stroke in elderly patients using seven modeling approaches to train the model. The diagnostic value of the model derived from machine learning was evaluated by the ROC curve (receiver operating characteristic curve).ResultsWe analyzed 7,128 and 661 patients from MIMIC-VI and MIMIC-III, respectively. The XGB (extreme gradient boosting) model got the highest AUC (area under the curve) of 0.78 (0.75–0.81), making it better than the other six models, Besides, we found that XGB model with databalancing was better than that without data balancing. Based on this prediction model, we found hypertension, cancer, congestive heart failure, chronic pulmonary disease and peripheral vascular disease were the top five predictors. Furthermore, we demonstrated that hypertension predicted postoperative stroke is much more valuable.ConclusionStroke in elderly patients during the postoperative period can be reliably predicted. We proved XGB model is a reliable predictive model, and the history of hypertension should be weighted more heavily than the results of laboratory tests to prevent postoperative stroke in elderly patients regardless of gender.

In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 ± 0.15 µg GAE/mg) and flavonoids (47.54 ± 0.45 µg QE/mg) with stronger antiradical effects through DPPH (IC50 = 16.66 ± 0.42 µg/mL), TAC (77.33 ± 0.41 µg AAE/mg) and TRP (79.11 ± 0.67 µg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC50 = 110.13 ± 1.71 µg/mL) activity through a modified Ellman’s method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.

Background: This study aimed to derive the effects of walking while using a mobile phone on balance perturbation and joint movement among young adults. Methods: Sixteen healthy college students with no history of brain injury were tested. The participants were asked to walk under four different conditions: (1) walking, (2) browsing, (3) dialing, and (4) texting. Indicators related to balance control and lower limb kinematic/kinetic parameters were analyzed using the continuous relative phase and statistical nonparametric mapping methods. Results: Walking while using a mobile phone slowed participants’ gait speed and reduced the cadence, stride length, and step length. The posterior tilt angle (0–14%, 57–99%), torque of the hip flexion (0–15%, 30–35%, 75–100%), and angle of the hip flexion (0–28%, 44–100%) decreased significantly. The activation of biceps femoris and gastrocnemius, hip stiffness, and ankle stiffness increased significantly. This impact on gait significantly differed among three dual tasks: texting > browsing > dialing. Conclusion: Che overlap of walking and mobile phone use affects the gait significantly. The “hip–ankle strategy” may result in a “smooth” but slower gait, while this strategy was deliberate and tense. In addition, this adjustment also increases the stiffness of the hip and ankle, increasing the risk of fatigue. Findings regarding this effect may prove that even for young healthy adults, walking with mobile phone use induces measurable adjustment of the motor pattern. These results suggest the importance of simplifying the control of the movement.

The feasibility of using microwaves to quickly stimulate automatic color change in 3D-printed food containing curcumin or anthocyanins was studied. Firstly, with a dual-nozzle 3D printer, stacked structures included mashed potatoes (MPs, upper part, containing anthocyanins) and lemon juice–starch gel (LJSG, lower part) were 3D-printed and post-treated using a microwave. The results indicated that the viscosity and gel strength (indicated by the elastic modulus (G′) and complex modulus (G*)) of LJSG were improved with the increase in starch concentration, while water mobility was reduced. During microwave post-treatment, the color change speed was negatively correlated with the gel strength but positively correlated with the diffusion of H+ and anthocyanin concentration. Secondly, nested structures were 3D-printed using MPs containing curcumin emulsion and baking soda (NaHCO3). During microwave post-treatment, the curcumin emulsion structure was destroyed, and NaHCO3 was decomposed, along with an increase in alkalinity; thus, the automatic color change was achieved with the automated presentation of hidden information. This study suggests that 4D printing could enable the creation of colorful and attractive food structures using a household microwave oven, leading to more imaginative solutions regarding personalized foods, which may be particularly important to people with poor appetites.

Extracting high-accuracy landslide areas using deep learning methods from high spatial resolution remote sensing images is a hot topic in current research. However, the existing deep learning algorithms are affected by background noise and landslide scale effects during the extraction process, leading to poor feature extraction effects. To address this issue, this paper proposes an improved mask regions-based convolutional neural network (Mask R-CNN) model to identify the landslide distribution in unmanned aerial vehicles (UAV) images. The improvement of the model mainly includes three aspects: (1) an attention mechanism of the convolutional block attention module (CBAM) is added to the backbone residual neural network (ResNet). (2) A bottom-up channel is added to the feature pyramidal network (FPN) module. (3) The region proposal network (RPN) is replaced by guided anchoring (GA-RPN). Sanming City, China was selected as the study area for the experiments. The experimental results show that the improved model has a recall of 91.4% and an accuracy of 92.6%, which is 12.9% and 10.9% higher than the original Mask R-CNN model, respectively, indicating that the improved model is more effective in landslide extraction.

Abstract This paper proposes a novel performance‐enhanced iterative learning control (ILC) scheme using a model‐free disturbance observer (DOB) to achieve high performance for precision motion systems that encounter non‐repetitive disturbances. As is well known, the performance of the standard ILC (SILC) is severely degraded by the non‐repetitive disturbances. By introducing DOB into SILC, this paper improves the robustness of the ILC system against non‐repetitive disturbances. In the proposed enhanced ILC (EILC), SILC aims at learning the feedforward signals for a specific reference, while DOB is to compensate for external disturbances. Little or no plant model knowledge is required for SILC. To maintain this advantage after introducing DOB, a model‐free design method for DOB is proposed to release the need for the plant model. Based only on a specific reference and the corresponding feedforward signals learned by SILC, the filter of DOB is optimized via an instrumental‐variable estimate method. Numerical simulation is performed to illustrate the effectiveness and enhanced performance of the proposed control approach.

Abstract Background Emerging oncogenes were reportedly linked to the complicated subtypes and pathogenesis of clinical gliomas. Herein, we first comprehensively explored the potential correlation between growth‐arrest‐specific two family genes (GAS2, GAS2L1, GAS2L2, GAS2L3) and gliomas by bioinformatics analysis and cellular experiments. Methods Based on the available datasets of TCGA (The Cancer Genome Atlas), CGGA (Chinese Glioma Genome Atlas), and Oncomine databases, we performed a series of analyses, such as gene expression, survival prognosis, DNA methylation, immune infiltration, and partner enrichment. We also utilized two glioma cell lines to conduct the colony formation and wound‐healing assay. Results GAS2L3 gene was highly expressed in glioma tissues compared to normal brain tissues (p

BackgroundEosinophilic leukemia (EL) is a rare, serious and potentially life-threatening condition characterized by the overproduction of eosinophils leading to tissue eosinophilic infiltration and damage. Although multiple organ systems may be involved, progressive eosinophilic myocarditis (EM) is the most common cause of morbidity and mortality. Early diagnosis and follow-up surveillance combined with multimodal imaging are crucial for appropriate treatment of EM.Case SummaryIt’s a rare case of EL with EM and intracardiac thrombus in a 59-year-old patient who presented with asthenia for 3 weeks. Full blood count analysis indicated significant eosinophilia. Bone marrow aspirate revealed dysplastic eosinophilia and a FIP1L1-PDGFRA fusion gene (4q12) was detected, confirming EL. Echocardiography revealed EM with intracardiac thrombus. This was later confirmed by cardiac magnetic resonance imaging. The patient was commenced on imatinib and prednisolone and good clinical response was obtained. Through 18F-FAPI PET/CT imaging, we obtained in vivo visualization of fibroblast activation changes in the early stage of cardiac structure remodeling. With anti-fibrotic therapy after heart failure, the patient achieved a good clinical response.ConclusionThis case demonstrates in vivo visualization of fibroblast activation after EM. Multimodality imaging can provide early diagnosis and may guide tailored antifibrotic therapy in early stage of EM.

Populus alba × Populus glandulosa (84K poplar) is model material with excellent genetic engineering resource and ornamental value. In our study, AmRosea1 (Antirrhinum majus) was overexpressed in 84K poplar, and the transgenic 84K (AM) poplar with high content of anthocyanin exhibited red pigmentation leaves. The transcriptome analysis between wild type (WT) and AM showed that 170 differentially expressed genes (DEGs) (86 up-regulated and 84 down-regulated) were found, and some DEGs were involved in flavone and flavonol biosynthesis, flavonoid biosynthesis and anthocyanin biosynthesis. The metabolome analysis showed that 13 anthocyanins-related differentially accumulated metabolites (DAMs) were detected in AM. The correlation analysis between DEGs and DAMs were performed, and the results revealed that 18 DEGs, including 11 MYB genes, two BZ1 genes, one FG2 gene, one ANS gene, and three IF7MAT genes, were negatively or positively correlated with 13 DAMs. The phylogenetic analysis demonstrated that there was high homology between AmRosea1 and PagMYB113, and MYB113 co-expressed with BZ1, ANS and DFR directly. Our results elucidated the molecular mechanism of plant color change mediated by anthocyanin biosynthesis pathway, which laid the foundation for the development and utilization of colorful woody plant.

AimsSex hormones play an important role in the pathogenesis of cardiovascular disease (CVD). This cross-sectional study aimed to explore the associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with coronary heart disease (CHD) and stroke in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).Materials and MethodsA total of 995 patients with T2DM were included in the study analysis. Serum levels of DHEA and DHEAS were quantified using liquid chromatography–tandem mass spectrometry. Binary logistic regression analyses were performed to assess the associations of DHEA and DHEAS with CHD and stroke. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal DHEA and DHEAS cutoff values for the detection of CHD in men with T2DM.ResultsIn men with T2DM, after adjustment for potential confounders in model 3, the risk of CHD decreased with an increasing serum DHEA level [odds ratio (OR) = 0.38, quartile 4 vs. quartile 1; 95% confidence interval (CI) = 0.16–0.90; p = 0.037 for trend). Consistently, when considered as a continuous variable, this association remained significant in the fully adjusted model (OR = 0.59, 95% CI = 0.40–0.87, p 0.05).ConclusionsSerum DHEA and DHEAS were significantly and negatively associated with CHD in middle-aged and elderly men with T2DM. This study suggests potential roles of DHEA and DHEAS in CHD pathogenesis.

Juglans mandshurica is a native tree species in Northeast China. Due to habitat destruction and human disturbance, its population size has sharply decreased. Currently, information on molecular markers of J. mandshurica is limited and cannot meet the needs of germplasm resource evaluation and molecular marker-assisted breeding of J. mandshurica. Based on transcriptomic data from three tissues (leaves, bark, and fruit pericarp), we developed expressed sequence tag-simple sequence repeats (EST-SSRs) for J. mandshurica, and 15 polymorphic EST-SSR primers were initially selected. The average number of alleles (Na), expected heterozygosity (He), and the polymorphic information content (PIC) at different loci were 18.27, 0.670, and 0.797, respectively. Population genetic diversity analysis revealed that the average Na, He, and Shannon information indices (I) for 15 J. mandshurica populations were 6.993, 0.670, and 1.455, respectively. Among them, population Hunchun exhibited the highest genetic diversity (Na = 7.933, He = 0.723, and I = 1.617), while population Heihe exhibited the lowest genetic diversity (Na = 4.200, He = 0.605, and I = 1.158). STRUCTURE analysis, neighbor-joining method cluster analysis, and principal coordinate analysis showed that the 343 individuals of J. mandshurica from 15 populations were clustered into three categories. Category 1 (green) had 147 individuals from eight populations in Qingyuan, Caohekou, Jian, Ningan, Yongji, Baishishan, Helong, and Maoershan; category 2 (blue) had 81 individuals from three populations in Hulin, Boli, and Sanchazi; and category 3 (red) had 115 individuals from four populations in Heihe, Hunchun, Fangzheng, and Liangshui. Analysis of molecular variance (AMOVA) showed that genetic variations among and within individuals accounted for 16.22% and 21.10% of the total genetic variation, respectively, indicating that genetic variations within populations were greater than genetic variations among populations. The average genetic differentiation coefficient (Fst) and gene flow (Nm) between different populations were 0.109 and 4.063, respectively, implying moderate levels of genetic differentiation and gene flow. Based on the genetic diversity characteristics of different populations, we proposed various genetic conservation strategies for J. mandshurica.

Objective: The objective of this trial is to evaluate and compare the acute toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with docetaxel plus cisplatin, or docetaxel, or cisplatin concurrently with helical tomotherapy during concurrent chemoradiotherapy (CCRT). Methods: In a prospective, single-center, open-label, randomized phase II study, after 2 cycles of induction chemotherapy with docetaxel plus cisplatin regimen, 125 patients with LA-NPC (stage III and IVA, UICC eighth) diagnosed pathologically from June 2017 to November 2019 were randomized into CCRT with docetaxel plus cisplatin group (25 patients), CCRT with docetaxel group (50 patients), and CCRT with cisplatin group (50 patients). The incidence of grade 3 or 4 acute toxicities and clinical efficacy were analyzed among the 3 groups. Results: Safety evaluation was completed in all the 125 patients, during the CCRT period, 66.4% of patients completed 3 cycles of chemotherapy, 24.0% completed 2 cycles of chemotherapy, and 9.6% completed 1 cycle of chemotherapy according to the research plan. The incidence of grade 3 or 4 acute toxicity in CCRT with docetaxel plus cisplatin (DP), docetaxel (D), and cisplatin (P) groups was 88.0%, 72.0%, and 56.0%, respectively. The incidence of grade 3 or 4 acute toxicities in the DP group was significantly higher than that in the D and P groups ( P = .015), no significant difference was detected between the D and P groups ( P = .096). The most common toxicities were mucositis (40.0%), leukopenia (29.6%), neutropenia (26.4%), and pharyngo-esophagitis (12.0%); compared to D and P groups, DP group did not significantly improved the 3-year overall survival (96.0% vs 87.0% and 87.6%), progression-free survival (92.0% vs 79.7% and,76.9%), locoregional failure-free survival (96.0% vs 91.8% and 92.7%), and distant failure-free survival (100% vs 90.0% and 89.0%), there were no significant difference in survival data among the 3 groups (all P > .05). Conclusions: Higher survival benefits did not achieve from intensified CCRT with DP, CCRT with P or D obtained similar short-term survival outcomes with similar acceptable toxicities in LA-NPC patients.

Background and AimFew non-invasive models were established to identify patients with non-alcoholic steatohepatitis (NASH). Liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to develop a non-invasive model incorporating CP for identifying NASH from NAFLD without type 2 diabetes mellitus (T2DM).MethodsA total of 138 biopsy-proven patients with NAFLD without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH in patients with NAFLD.ResultsThe medians of the high (n = 69) and low (n = 69) CP ratio groups were 1.43 (1.28–1.61) and 1.03 (0.94–1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p < 0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01–1.41) vs. 1.33 (1.24–1.54), p = 0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD was 0.796 (0.694–0.899) and 0.849 (0.713–0.984) in the training and validation groups, and 0.836 (0.659–1.000), 0.833 (0.705–0.962), and 0.821 (0.612–1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively.ConclusionsDecreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among patients with NAFLD without T2DM. The CP ratio model could be served as a non-invasive approach to identifying patients with NASH, which might reduce the need for liver biopsy.

BackgroundThe associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with diabetic kidney disease (DKD) remained unclear. Thus, this cross-sectional study aimed to explore the associations of DHEA and DHEAS with the risk of DKD in patients with T2DM.MethodsThe information of 1251 patients with T2DM were included in this study. Serum DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry assays. Multivariate logistic regression analyses were used to assess the associations of DHEA and DHEAS with DKD as well as high urine albumin to creatinine ratio (ACR).ResultsIn men with T2DM, the risk of DKD decreased with an increasing DHEA concentration after adjustment for traditional risk factors; the fully adjusted OR (95% CI) for tertile3 vs tertile1 was 0.37 (0.19-0.70; P = 0.010 for trend). Similarly, when taking high ACR as the outcome, low DHEA levels were still significantly associated with increased odds of high ACR (OR, 0.37; 95% CI, 0.19–0.72 for tertile3 vs tertile1; P = 0.012 for trend). The restricted cubic spline showed that the risk of DKD gradually decreased with the increment of serum DHEA levels (P-overall = 0.007; P-nonlinear = 0.161). DHEAS was not independently associated with the risk of DKD in men. In contrast, no significant relationships were found between DHEA and DHEAS and the risk of DKD in women (all P > 0.05).ConclusionsIn men with T2DM, low serum DHEA levels were independently related to the risk of DKD after adjustment for traditional risk factors. Our finding highlights the potential role of DHEA in the development of DKD in men with T2DM.

The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.

Machine learning (ML) is increasingly deployed on biomedical studies for biomarker development (feature selection) and diagnostic/prognostic technologies (classification). While different ML techniques produce different feature sets and classification performances, less understood is how upstream data processing methods (e.g., normalisation) impact downstream analyses. Using a clinical mental health dataset, we investigated the impact of different normalisation techniques on classification model performance. Gene Fuzzy Scoring (GFS), an in-house developed normalisation technique, is compared against widely used normalisation methods such as global quantile normalisation, class-specific quantile normalisation and surrogate variable analysis. We report that choice of normalisation technique has strong influence on feature selection. with GFS outperforming other techniques. Although GFS parameters are tuneable, good classification model performance (ROC-AUC > 0.90) is observed regardless of the GFS parameter settings. We also contrasted our results against local modelling, which is meant to improve the resolution and meaningfulness of classification models built on heterogeneous data. Local models, when derived from non-biologically meaningful subpopulations, perform worse than global models. A deep dive however, revealed that the factors driving cluster formation has little to do with the phenotype-of-interest. This finding is critical, as local models are often seen as a superior means of clinical data modelling. We advise against such naivete. Additionally, we have developed a combinatorial reasoning approach using both global and local paradigms: This helped reveal potential data quality issues or underlying factors causing data heterogeneity that are often overlooked. It also assists to explain the model as well as provides directions for further improvement.

ObjectiveTo develop and evaluate the performance of a magnetic resonance imaging (MRI)-based radiomics nomogram for prediction of response of patients with muscle-invasive bladder cancer (MIBC) to neoadjuvant chemotherapy (NAC).MethodsA total of 70 patients with clinical T2-4aN0M0 MIBC were enrolled in this retrospective study. For each patient, 1316 radiomics features were extracted from T2-weighted images (T2WI), diffusion-weighted images (DWI), and apparent diffusion coefficient (ADC) maps. The variance threshold algorithm and the Student’s t-test or the Mann–Whitney U test were applied to select optimal features. Multivariate logistic regression analysis was used to eliminate irrelevant features, and the retained features were incorporated into the final single-modality radiomics model. Combined radiomic models were generated by combining single-modality radiomics models. A radiomics nomogram, incorporating radiomics signatures and independent clinical risk factors, was developed to determine whether the performance of the model in predicting tumor response to NAC could be further improved.ResultsBased on pathological T stage post-surgery, 36 (51%) patients were classified as good responders (GR) and 34 (49%) patients as non-good responders (non-GR). In addition, 3 single-modality radiomics models and 4 combined radiomics models were established. Among all radiomics models, the combined radiomics model based on T2WI_Score, DWI_Score, and ADC_Score yielded the highest area under the receiver operating characteristics curve (AUC) (0.967, 95% confidence interval (CI): 0.930–0.995). A radiomics nomogram, integrating the clinical T stage and 3 single-modality radiomics models, yielded a higher AUC (0.973, 95%CI: 0.934–0.998) than other combined radiomics models.ConclusionThe proposed MRI-based radiomics nomogram has the potential to be used as a non-invasive tool for the quantitatively prediction of tumor response to NAC in patients with MIBC.

Rural energy is related to the domestic energy supply, consumption, and improvement of living standards of more than one-third of the population in China. In the “14th Five-Year Plan,” it has been clearly pointed out that it is necessary to strengthen the clean utilization of coal and implement the construction of rural clean energy projects. At present, the energy consumption structure of rural areas in China is transiting from traditional solid energy to commercial energy and clean energy. Based on this background, this paper reviews the transition trend, influencing factors, and regional differences of China’s rural household energy consumption structure from the 1990s. Taking into account China’s goal of carbon peaking by 2030 and carbon neutrality by 2060, carbon dioxide and pollutant emissions generated in the process of energy consumption and the energy-saving potential of rural households are analyzed and discussed. Moreover, the evolution of rural energy policies in China is presented and related proposals are also made. This review aims to provide reference for relevant researchers and policy makers.

To produce an edible film with high mechanical and physicochemical properties, Tuna skin collagen-chitosan (TSC-CTS) composite films were prepared by incorporating ultrasound (UT) and pomegranate polyphenols including gallic acid (GA), tannic acid (TA), and ellagic acid (EA), respectively. The tensile strength and the DPPH scavenging activity of the GA-UT-TSC-CTS film (ultrasound frequency of 28 ± 0.5 kHz, power of 100 W/L, sweep frequency cycle of 100 ms, duty ratio of 77% and time of 10 min; GA concentration of 1.0 g/L and reaction time of 10 min) were increased by 47.03% and 24.16 folds, respectively compared to the control (TSC-CTS film). Meanwhile, light transmittance and water vapor permeability of the GA-UT-TSC-CTS film were decreased by 29.26% and 15.70%, respectively. These positive modification results were attributed to the altered structure during the film formation process, which were verified by Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), X-ray diffraction (XRD), and thermogravimetry results. Moreover, the GA-UT-TSC-CTS film possessed moderate thermal stability and color indexes and improved antibacterial activity. The antibacterial effect of the film against Bacillus subtilis was the highest, followed by Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus. Overall, the combination modification of gallic acid and ultrasound was an efficient modification method to improve the mechanical, antioxidant, and antibacterial properties of edible TSC-CTS films.

Argon-ion polishing field emission-scanning electron microscopy (FE-SEM) is a common method to characterize the microscopic pore structure characteristics of shale reservoirs, but organic macerals cannot be directly identified by FE-SEM alone. Fluorescence microscopy is the main method for identifying macerals. Through a large number of localized FE-SEM and fluorescence microscopy observations, the microscopic characteristics of specific macerals under FE-SEM were summarized. The macerals visualized using FE-SEM can be interpreted based on features such as the external shape, hardness, brightness, color, relief, organic pore development characteristics and fissure development characteristics of the organic matter. Telinite, collotelinite, vitrodetrinite, fusinite, semifusinite, funginite, inertodetrinite, oil bitumen and pyrobitumen were identified.

Abstract Background FBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear. Methods The correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development. Results Decreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored LUAD cell suppression in vitro and in vivo. Conclusions Our findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.

Abstract The quality of Citri Reticulatae Pericarpium (CRP) is closely correlated with the aging time. However, CRPs in different storage ages are similar in appearance, and the young CRP may be labeled as the aged one to obtain the excess profit by some unscrupulous traders. Most traditional analysis methods are laborious and time‐consuming, and they can hardly realize the nondestructive classification. In this paper, a novel method based on near‐infrared diffuse reflectance spectroscopy (NIRDRS) and data combination technique for the nondestructive classification of different‐age CRPs was proposed. The CRPs in different storage ages (5, 10, 15, 20, and 25 years) were measured. The near‐infrared spectra of outer skin and inner capsule were obtained. Principal component analysis (PCA), soft independent modeling of class analogy (SIMCA), and Fisher's linear discriminant analysis (FLD), with different data pretreatment methods, were used for the classification analysis. Data combination of the outer skin and inner capsule spectra was discussed for further improving the classification results. The results show that multiple sensors provide more useful and complementary information than a single sensor does for improving the prediction accuracy. With the help of data combination strategy, 100% prediction accuracy can be obtained with both second‐order derivative–FLD and continuous wavelet transform–multiplicative scatter correction–FLD methods.

Abstract Background Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. Methods All male Apolipoprotein E-deficient (ApoE−/−) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages. Results Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE−/− mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. Conclusions Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

Abstract Cataract surgery is the most common intraocular procedure. To decrease postsurgical inflammation, prevent infection and reduce the incidence of secondary cataract, we built a temperature-sensitive drug delivery system carrying dexamethasone, moxifloxacin and genistein nanostructured lipid carrier (GenNLC) modified by mPEG-PLA based on F127/F68 as hydrogel. Characterizations and release profiles of the drug delivery system were studied. In vitro functions were detected by CCK-8 test, immunofluorescence, wound-healing assay, real time-PCR and western blotting. The size of GenNLCs was 39.47 ± 0.69 nm in average with surface charges of − 4.32 ± 0.84 mV. The hydrogel gelation temperature and time were 32 °C, 20 s with a viscosity, hardness, adhesiveness and stringiness of 6.135 Pa.s, 54.0 g, 22.0 g, and 3.24 mm, respectively. Transmittance of the gel-release medium was above 90% (93.44 ± 0.33% to 100%) at range of 430 nm to 800 nm. Moxifloxacin released completely within 10 days. Fifty percent of dexamethasone released at a constant rate in the first week, and then released sustainably with a tapering down rate until day 30. Genistein released slowly but persistently with a cumulative release of 63% at day 40. The thermoresponsive hydrogel inhibited the proliferation, migration and epithelial-mesenchymal transition of SRA 01/04 cells, which were confirmed by testing CCK-8, wound-healing assay, western blot, real time-PCR (RT-PCR) and immunofluorescence. These results support this intracameral thermoresponsive in situ multi-drug delivery system with programmed release amounts and release profiles to cut down the need of eye drops for preventing inflammation or infection and to reduce posterior capsular opacification following cataract surgery.

Few non-invasive models were established for precisely identifying the immune tolerant (IT) phase from chronic hepatitis B (CHB). This study aimed to develop a novel approach that combined next-generation sequencing (NGS) and machine learning algorithms using our recently published viral quasispecies (QS) analysis package. 290 HBeAg positive patients from whom liver biopsies were taken were enrolled and divided into a training group (n = 148) and a validation group (n = 142). HBV DNA was extracted and QS sequences were obtained by NGS. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) based on viral operational taxonomic units (OTUs) were performed to explore the correlations among QS and clinical phenotypes. Three machine learning algorithms, including K-nearest neighbour, support vector machine, and random forest algorithm, were used to construct diagnostic models for IT phase classification. Based on histopathology, 90 IT patients and 200 CHB patients were diagnosed. HBsAg titres for IT patients were higher than those of CHB patients (p