Search

Periodontal disease (PD) is a local inflammatory disease with high morbidity, manifesting tissue destruction results from inflammation of the host immune response to bacterial antigens and irritants. The supportive function of connective tissue and skeletal tissue can be jeopardized without prompt and effective intervention, representing the major cause of tooth loss. However, traditional treatments exhibited great limitations, such as low efficacies, causing serious side effects and recurrent inflammatory episodes. As a major defense mechanism, reactive oxygen species (ROS) play important roles in the pathological progression of PD. Antioxidant therapy is widely believed to be an effective strategy for ROS-triggered diseases, including oxidative stress-induced PD. Most antioxidants can only scavenge one or a few limited kinds of ROS and cannot handle all kinds. In addition, current antioxidant nanomaterials present limitations associated with toxicity, low stability, and poor biocompatibility. To this end, we develop ultra-small molybdenum-based nanodots (MoNDs) with strong ROS in oxidative stress-induced PD. To the best of our knowledge, this is the first time that MoNDs have been used for PD. In the present study, MoNDs have shown extremely good therapeutic effects as ROS scavengers. Spectroscopic and in vitro experiments provided strong evidence for the roles of MoNDs in eliminating multiple ROS and inhibiting ROS-induced inflammatory responses. In addition, the mouse model of PD was established and demonstrated the feasibility of MoNDs as powerful antioxidants. It can alleviate periodontal inflammation by scavenging multiple ROS without obvious side effects and exhibit good biocompatibility. Thus, this newly developed nanomedicine is effective in scavenging ROS and inhibiting M1 phenotypic polarization, which provides promising candidates for the treatment of PD.

BackgroundIn clinical practice, oral probiotics are often given to children with hyperbilirubinaemia who receive phototherapy, but the exact mechanism of the action of the probiotics on hyperbilirubinaemia remains unclear. It is unclear how the effects of phototherapy on the probiotic flora in the neonatal gut, in particular.Materials and methodsFifty newborns who needed phototherapy from June 2018 to June 2020 were selected as the study subjects, and five healthy newborns in the same period were used as controls to analyse the changes in probiotic bacteria in their faeces.Results1. In the intestinal tracts of newborns, Bifidobacterium is the main probiotic strain, with a small amount of Lactobacillus. There were probiotic species changes in the neonatal intestinal microbiota after phototherapy for 24 and 48 h. The amount of Bifidobacterium and Lactobacillus decreased significantly (P < 0.05). 2. A correlation analysis of probiotic species and bile acid metabolism indexes showed that Bifidobacterium was positively correlated with many metabolites (P < 0.05), such as chenodeoxycholic acid, hyodeoxycholic acid, cholic acid, allocholic acid, and β-cholic acid. It was also negatively correlated with many metabolites (P < 0.05), such as glycocholic acid, sodium, sodium tudca, and chenodeoxycholic acid. Lactobacillus was negatively correlated with metabolites (P < 0.05) such as α-sodium cholate and β-cholic acid. 3. A correlation analysis between the changes in probiotics and intestinal short-chain fatty acid metabolites after phototherapy showed that acetic acid, butyric acid, caproic acid, and propionic acid decreased and were significantly correlated with Bifidobacterium (P < 0.05). 4. After phototherapy, 17 metabolites changed significantly (P < 0.05). This correlated with many probiotics (P < 0.05). The significantly changed probiotics in this study showed a significant correlation with some intestinal metabolites (P < 0.05).ConclusionIt was found that phototherapy can significantly affect the intestinal probiotic flora and the metabolic indicators of newborns, which may be an important reason for the side effects of phototherapy, and also provides the theoretical basis for the provision of probiotics to newborns with jaundice.

Drug-induced liver injury (DILI) is a serious clinical disease associated with reactive oxygen species (ROS) burst and subsequent inflammatory responses. However, traditional treatments were limited by low efficacy and serious side effects due to the special liver structure. Here, we developed a molybdenum (Mo)-based nanoparticles, EGM NPs, after overall consideration of the pathophysiology of DILI and the advantages of nanodrugs. It demonstrated that EGM NPs treated acetaminophen (APAP)-induced DILI by scavenging ROS and inhibiting inflammation. EGM NPs effectively scavenged various ROS and reduced cell apoptosis at the cellular level. More importantly, EGM NPs can treat APAP-induced DILI in vivo, reducing the levels of liver function indicators in mice with liver injury, scaling down the area of hepatocyte necrosis and successfully inhibiting endoplasmic reticulum (ER) stress in the liver. EGM NPs also showed a certain anti-inflammatory effect by reducing infiltration of macrophages, decreasing pro-inflammatory factors and inhibiting the expression levels of inducible nitric oxide synthase (NOS2) and myeloperoxidase (MPO). Collectively, our findings suggest that EGM NPs-based nanotherapeutic is a novel strategy for the treatment of DILI.

Abstract Background LYRM4 is necessary to maintain the stability and activity of the human cysteine desulfurase complex NFS1-LYRM4-ACP. The existing experimental results indicate that cancer cells rely on the high expression of NFS1. However, the role of LYRM4 in liver hepatocellular carcinoma (LIHC) remains unclear. Methods In this study, we combined bioinformatics analysis and clinical specimens to evaluate the mRNA, protein expression, and gene regulatory network of LYRM4 in LIHC. Furthermore, we detected the activity of several classical iron-sulphur proteins in LIHC cell lines through UV-vis spectrophotometry. Results The mRNA and protein levels of LYRM4 were upregulated in LIHC. Subsequent analysis revealed that the LYRM4 mRNA expression was related to various clinical stratifications, prognosis, and survival of LIHC patients. In addition, the mRNA expression of LYRM4 was significantly associated with ALT, tumour thrombus, and encapsulation of HBV-related LIHC patients. IHC results confirmed that LYRM4 was highly expressed in LIHC tissues and showed that the expression of LYRM4 protein in LIHC was significantly correlated with age and serum low-density lipoprotein (LDL) and triglyceride (TG) content. In particular, the mRNA expression of key iron- sulphur proteins POLD1 and PRIM2 was significantly overexpressed and correlated with poor prognosis in LIHC patients. Compared with hepatocytes, the activities of mitochondrial complex I and aconitate hydratase (ACO2) in LIHC cell lines were significantly increased. These results indicated that the iron-sulphur cluster (ISC) biosynthesis was significantly elevated in LIHC, leading to ISC-dependent metabolic reprogramming. Changes in the activity of ISC-dependent proteins may also occur in paracancerous tissues. Further analysis of the biological interaction and gene regulation networks of LYRM4 suggested that these genes were mainly involved in the citric acid cycle and oxidative phosphorylation. Finally, LYRM4 expression in LIHC was significantly positively correlated with the infiltrating levels of six immune cell types, and both factors were strongly associated with prognosis. Conclusion LYRM4 could be a novel prognostic biomarker and molecular target for LIHC therapy. In particular, the potential regulatory networks of LYRM4 overexpression in LIHC provide a scientific basis for future research on the role of the ISC assembly mechanism and LYRM4-mediated sulphur transfer routes in carcinogenesis.

In order to forecast flood accurately and reveal the relationship between rainstorm and flood at the micro level, a model which combines wavelet analysis, GM (1,2) and fuzzy weighted Markov is built. Taking the Jialu River of Zhengzhou City in China as study area, the GM (1,2) model is constructed between the components of rainfall and flood volume by wavelet decomposition to connect the two variables, then a fuzzy weighted Markov method is introduced to correct the predicted component of flood volume. The corrected results are superimposed to obtain the predicted value of flood. To verify the reliability of the model, the maximum daily, 3-, 5- and 7-day flood volume of the next five floods in Zhongmu and Jiangang hydrological stations are predicted in turn. The results show that the multi-scale flood forecasting model has high overall forecasting accuracy, with the average relative errors all less than 10%. The forecasting accuracy of maximum five-day flood volume is higher than other periods. On the micro level, the results indicate that the fluctuation trend and period of rainfall-flood volume in d1, d2 and d3 are basically the same. Among the components of forecasted flood, the impact of rainfall on flood volume is most significant in the d3 component. HIGHLIGHTS Combining GM (1,2) with wavelet analysis can reveal the relationship between rainfall and flood volume at the micro level, so as to better reflect the physical mechanism between them.; The forecasted flood volume is reflected not only at the macro level but also at the micro level.; Using the fuzzy weighted Markov method to correct the predicted components, then the prediction model has a favorable prediction effect.;

In this paper, the application of NACA airfoil pillar-shaped flumes and the influence of their wing lengths on flow measurement characteristics are discussed. The standard k-ε three-dimensional turbulence model and the volume of fluid (VOF) method were used for numerical simulation of the flow in six NACA airfoil pillar-shaped flumes with different wing lengths. In addition, to verify the accuracy of numerical simulations, the corresponding experiments were conducted. The Buckingham Pi theorem of dimensional analysis coupled with the incomplete self-similarity theory was applied to deduce the theoretical flow calculation formula of these flumes. Moreover, Froude number, velocity distribution, backwater height, critical submergence, and energy loss of the flume were analyzed, for which the experimental and numerical results are compared and further discussed. The results show that the backwater height is directly proportional to the wing length, while the head loss and critical submergence are inversely proportional to the wing length. Based on the results, in terms of backwater height, it is recommended to use the NACA airfoil pillar-shaped flume with a smaller wing length, while, in terms of head loss and critical submergence, the NACA airfoil pillar-shaped flume with a larger wing length should be used. HIGHLIGHTS The application of NACA airfoil pillar-shaped flumes is discussed.; The Buckingham Pi theorem of dimensional analysis coupled with the incomplete self-similarity theory is applied to deduce the theoretical flow calculation formula.; Laboratory experiments and numerical simulations are combined to provide a theoretical reference for applications of this flume.;

In order to survey the possible periodic, uncertainty and common features in runoff with multi-temporal scales, the empirical mode decomposition (EMD) method combined with the set pair analysis (SPA) method was applied, with data observed at Zhangjiashan hydrological station. The results showed that the flood season and annual runoff time series consisted of four intrinsic mode function (IMF) components, and the non-flood season time series exhibited three IMF components. Moreover, based on the different coupled set pairs from the time series, the identity, discrepancy, and contrary of different periods at multi-temporal scales were determined by the SPA method. The degree of connection μ between the flood season and annual runoff periods were the highest, with 0.94, 0.77, 0.7 and 0.73, respectively, and the μ between the flood periods and the non-flood periods were the lowest, with 0.66, 0.46, 0.24 and 0.24, respectively. Third, the maximum μ of each SPA appeared in the first mode function. In general, the different extractive periods decomposed by the EMD method reflected the average state of Jinghe River. Results also verified that runoff suffered from seasonal and periodic fluctuations, and fluctuations in the short-term corresponded to the most important variable. Therefore, the conclusions drawn in this study can improve water resources regulation and planning. HIGHLIGHTS A coupling model of empirical mode decomposition and set pair analysis is proposed.; Mutation and variation of runoff under different time scales is provided.; Trend components and fluctuation features under multi-temporal scales are explored.;

Purpose: Taxifolin (TAX) is a flavanol compound with hepatoprotective effect, but its application is severely limited by its poor water solubility and low oral bioavailability. Therefore, it is important to urgently find a method to improve the oral bioavailability of TAX. Methods: In this study, hydroxypropyl methylcellulose acetate succinate modified taxifolin liposomes (HPMCAS-TAX-Lips) were prepared by a thin-film dispersion method, and a series of physicochemical properties of the liposomes were studied. The cumulative in vitro release rates of free TAX, taxifolin liposomes (TAX-Lips), and HPMCAS-TAX-Lips in the simulated gastrointestinal fluid were measured by in vitro release experiments, and the effect of HPMCAS-TAX-Lips on the human hepatoellular carcinomas (HepG2) cells was detected by MTT assay. Finally, the hepatoprotective mechanism of HPMCAS-TAX-Lips was explored through in vivo experiments. Results: The results showed that the particle size of HPMCAS-TAX-Lips was 100.44 ± 2.85 nm, the zeta potential was − 51.13 ± 0.57 mV, the PDI was 0.170 ± 0.088, and the EE was 87.9 ± 3.73%. The in vitro release results showed that the cumulative release rates of TAX-Lips and HPMCAS-TAX-Lips in simulated gastric fluid for 24 h were 92.60 ± 5.31% and 66.91 ± 1.20%, respectively. The cumulative release rates in simulated intestinal fluid for 24 h were 72.61 ± 4.38% and 53.94 ± 3.2%, respectively. The results of cytotoxicity experiments proved that HPMCAS-TAX-Lips had a significant inhibitory effect on HepG2 cells. In vivo experiments further showed that HPMCAS-TAX-Lips significantly improved the survival rate of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury mice and exerted hepatoprotective effects by regulating the expression of autophagy proteins and inhibiting the activation of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. Conclusion: This study proved the significant hepatoprotective effect of HMPCAS-TAX-Lips and provided a new idea for the application of TAX.

Gastric cancer remains one of the major contributors to global cancer mortality, although there is no promising target drug in clinics. Hence, the identification of novel targeted drugs for gastric cancer is urgent. As a promising strategy for inducing ferroptosis for gastric cancer treatment, the ferroptosis inducer is a potential drug. Nevertheless, no ferroptosis inducer has entered clinics. So, our purpose was to identify a novel ferroptosis inducer for gastric cancer treatment using a drug repurposing strategy. Firstly, using a drug repurposing strategy with the aid of a commercialized compound library, HC-056456, a small molecule bioactive CatSper channel blocker, was characterized to inhibit the growth of gastric cancer line MGC-803. At the same time, this anti-proliferation effect can be blocked by ferrostatin-1, a ferroptosis inhibitor, indicating that HC-056456 is a ferroptosis inducer. Then, HC-056456 was identified to decrease GSH content via p53/SLC7A11 signaling pathway. Then Fe2+ and lipid peroxide were accumulated when cells were exposed to HC-056456. Finally, HC-056456 was found to suppress the growth of gastric cancer cells by increasing p53 and repressing SLC7A11 in vivo but not in the presence of ferrostatin-1. In sum, we systematically elucidate that HC-056456 exerts anti-gastric cancer effect by provoking ferroptosis in vitro and in vivo, suggesting its potential role in gastric cancer treatment.

The panax genus is a widely used medicinal plant with good biological activity. As one of the main active components of the Panax genus, polysaccharides have various pharmacological effects. This review summarizes the latest research reports on ginseng, American ginseng, and Panax notoginseng polysaccharides and compares the differences in extraction, isolation and purification, structural characteristics, and biological activities. The current research mainly focuses on ginseng polysaccharides, and the process of extraction, isolation, and structure analysis of each polysaccharide is roughly the same. Modern pharmacological studies have shown that these polysaccharides have antioxidants, antitumor, immunomodulatory, antidiabetic, intestinal protection, skin repair, and other biological activities. This review provides new insights into the differences between the three kinds of ginseng polysaccharides which will help to further study the medicinal value of ginseng in traditional Chinese medicine.

In distant hybridization of fishes, there is a low hatching rate of hybrid progenies. To further understand the causes of low hatchability, in this article, cross-breeding between zebrafish (ZF) and crucian carp (CC) are generated, in which the hatching rate of cross progenies (ZF♀ × CC♂, ZC) is 35.67%, while that of reciprocal cross progenies (CC♀ × ZF♂, CZ) is about zero. The structures and SDS-PAGE protein pattern of egg envelopes in hybrid early embryos are like their maternal fish, however, during the process of embryo development, some differences are detected between the CZ and CC. The hatching enzyme gene 1 (he1) nucleotide sequences from ZF and CC were 85.1% identity, while that of 99.6% identity was between the ZF and ZC, and 98.4% from CC and hybrid of CZ. There are differences in predictive protein physicochemical properties of he1 between CZ and CC, but no significant change in he1 mRNA levels during embryonic development. Our data furtherly verify that the characteristics of egg envelope and hatching enzyme in hybrid progenies are inherited from maternal fish. Moreover, there are obvious differences between CZ and maternal parent in both egg envelope and hatching enzyme during embryonic development, which are considered to be related to its low hatching rate.

To reveal the effects of rainfall and runoff-yield conditions on runoff, the abrupt change of the correlation between rainfall and runoff is discussed. Then, according to the correlation between rainfall and runoff with the different rainfall states, the multivariate dynamic regression models of rainfall and runoff are constructed, and the effects of rainfall and runoff-yield conditions on runoff are analyzed. The results show that (1) the correlation between rainfall and runoff changed abruptly in 1980; (2) the rainfall changes lead to runoff reductions, and runoff decreased by 15.79% under the runoff-yield condition Ⅰ from 1959 to 1979, while it decreased by 8% under the runoff-yield condition Ⅱ from 1980 to 2013; (3) the change of the runoff-yield conditions lead to the runoff reduction of 41.16% from 1959 to 1979, while it leads to a decrease in runoff by 35.58% from 1980 to 2013.

Abstract Background Brown marmorated stink bug (BMSB), Halyomorpha halys (Hemiptera: Pentatomidae) is native to East Asia but has invaded many countries in the world. BMSB is a polyphagous insect pest and causes significant economic losses to agriculture worldwide. Knowledge on the genetic diversity among BMSB populations is scarce but is essential to understand the patterns of colonization and invasion history of local populations. Efforts have been made to assess the genetic diversity of BMSB using partial mitochondrial DNA sequences but genetic divergence on mitochondria is not high enough to precisely accurately identify and distinguish various BMSB populations. Therefore, in this study, we applied a ddRAD (double digest restriction-site associated DNA) sequencing approach to ascertain the genetic diversity of BMSB populations collected from 12 countries (2 native and 10 invaded) across four continents with the ultimate aim to trace the origin of BMSBs intercepted during border inspections and post-border surveillance. Result A total of 1775 high confidence single nucleotide polymorphisms (SNPs) were identified from ddRAD sequencing data collected from 389 adult BMSB individuals. Principal component analysis (PCA) of the identified SNPs indicated the existence of two main distinct genetic clusters representing individuals sampled from regions where BMSB is native to, China and Japan, respectively, and one broad cluster comprised individuals sampled from countries which have been invaded by BMSB. The population genetic structure analysis further discriminated the genetic diversity among the BMSB populations at a higher resolution and distinguished them into five potential genetic clusters. Conclusion The study revealed hidden genetic diversity among the studied BMSB populations across the continents. The BMSB populations from Japan were genetically distant from the other studied populations. Similarly, the BMSB populations from China were also genetically differentiated from the Japanese and other populations. Further genetic structure analysis revealed the presence of at least three genetic clusters of BMSB in the invaded countries, possibly originating via multiple invasions. Furthermore, this study has produced novel set of SNP markers to enhance the knowledge of genetic diversity among BMSB populations and demonstrates the potential to trace the origin of BMSB individuals for future invasion events.

Taxifolin (TAX) is a hepatoprotective flavanol compound, which is severely limited by poor solubility and low bioavailability. Liposomes (Lips) are used as well-recognized drug carrier systems that improve the water solubility and bioavailability of drugs, but are easily damaged by gastric juice after oral administration, resulting in the release of drugs in the gastric juice. Therefore, it is important to find materials that modify liposomes and avoid the destruction of the liposomal phospholipid bilayer structure by the gastrointestinal environment. Taxifolin liposomes (TAX-Lips) were modified by polyvinylpyrrolidone-k30 (PVP-TAX-Lips) and manufactured using a thin-film hydration technique. Particle size (109.27 ± 0.50 nm), zeta potential (−51.12 ± 3.79 mV), polydispersity coefficient (PDI) (0.189 ± 0.007), and EE (84.7 ± 0.2%) of PVP-TAX-Lips were studied. In addition, the results of in vitro release experiments indicated that the cumulative release rates of TAX-Lips and PVP-TAX-Lips were 89.73 ± 5.18% and 65.66 ± 4.86% in the simulated gastric fluid after 24 h, respectively, while the cumulative release rates were 68.20 ± 4.98% and 55.66 ± 3.92% in the simulated intestinal fluid after 24 h, respectively. Moreover, PVP-TAX-Lips were able to reverse lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced acute liver injury (ALI) by inducing autophagy to inhibit the expression levels of the TLR4/NF-κB signaling pathway and inflammatory factors, which suggested that PVP-TAX-Lips played an important role in the prevention of ALI and also provided a promising drug delivery system for the application of TAX.

Abstract Immunotherapy with toll like receptor 9 (TLR9) agonist CpG ODN offers an emergent strategy to treat life‐threatening malignant glioma. CpG is typically applied invasively by intracranial and intrathecal administration which induces not only poor compliance and lessened potency but also possibly strong adverse effects and immunotoxicity. Here, it is reported that immunotherapy of murine LCPN glioma is greatly boosted by polymersome‐steered intravenous and intranasal brain delivery of CpG. CpG is efficiently loaded in apolipoprotein E peptide‐directed polymersomes to give blood‐brain barrier permeable and glioma and cervical lymph node‐homing CpG nano‐immunoadjuvant (t‐NanoCpG) which strongly stimulates the maturation of dendritic cells, antigen cross‐presentation, and production of proinflammatory cytokines in vivo. Intriguingly, both intravenous and intranasal administration of t‐NanoCpG brings about significant survival benefits in murine LCPN glioma‐bearing mice while free CpG and nontargeted CpG nano‐immunoadjuvant (NanoCpG) afford modest therapeutic effects. Moreover, combination of t‐NanoCpG with radiotherapy further boosts the immunotherapeutic effects leading to more improved survival rate of mice. This intelligent brain‐permeable nano‐immunoadjuvant provides a new, minimally invasive and highly potent strategy for immunotherapy of glioma.

Cancer cell lysosomes contain various hydrolases and non-degraded substrates that are corrosive enough to destroy cancer cells. However, many traditional small molecule drugs targeting lysosomes have strong side effects because they cannot effectively differentiate between normal and cancer cells. Most lysosome-based research has focused on inducing mild lysosomal membrane permeabilization (LMP) to release anticancer drugs from lysosomal traps into the cancer cell cytoplasm. In fact, lysosomes are particularly powerful “bombs”. Achieving cancer cell-selective LMP induction may yield high-efficiency anticancer effects and extremely low side effects. Nanodrugs have diverse and combinable properties and can be specifically designed to selectively induce LMP in cancer cells by taking advantage of the differences between cancer cells and normal cells. Although nanodrugs-induced LMP has made great progress recently, related reviews remain rare. Herein, we first comprehensively summarize the advances in nanodrugs-induced LMP. Next, we describe the different nanodrugs-induced LMP strategies, namely nanoparticles aggregation-induced LMP, chemodynamic therapy (CDT)-induced LMP, and magnetic field-induced LMP. Finally, we analyze the prospect of nanodrugs-induced LMP and the challenges to overcome. We believe this review provides a unique perspective and inspiration for designing lysosome-targeting drugs.

Aspergillus fumigatus is an important pathogen causing invasive aspergillosis, which is associated with high morbidity and mortality in immunocompromised people. However, the treatment of A. fumigatus infection is a growing challenge, owing to the limited availability antifungal agents and the continual emergence of drug-resistant strains. Drug repurposing is a potential strategy to solve this current problem. Sodium new houttuyfonate (SNH), derived from houttuynin, extracted from Houttuynia cordata, has anti-bacterial and anti-Candida albicans effects. However, whether it has anti-A. fumigatus activity had not been reported. In this study, the antifungal properties of SNH against A. fumigatus, including the standard strain AF293, itraconazole resistant clinical strains, and voriconazole resistant clinical strains, were evaluated in vitro and in vivo. Moreover, the potential mechanism of SNH was characterized. SNH exhibited significant fungicidal activity toward various A. fumigatus strains. SNH also inhibited fungal growth, sporulation, conidial germination and pigment formation, and biofilm formation. Further investigations revealed that SNH interfered with the A. fumigatus cell steroid synthesis pathway, as indicated by transcriptomic and quantitative real-time polymerase chain reaction analyses, and inhibited ergosterol synthesis, as indicated by cell membrane stress assays and ergosterol quantification. Moreover, daily gastric gavage of SNH significantly decreased the fungal burden in mice with disseminated infection (kidney, liver, and lung) and local tissue damage. In addition, the application of SNH downregulated the production of IL-6 and IL-17A. Together, these findings provided the first confirmation that SNH may be a promising antifungal agent for the treatment of A. fumigatus infection.

Non-Hodgkin’s lymphoma (NHL) is a form of tumor that originates in the lymphoid tissues. Bacterial infections are very common in NHL patients. Because most of the patients do not experience apparent symptoms during the initial stage of infection, it is difficult to detect the underlying condition before it progresses to a more critical level. The activation of the cytokines is a hallmark of inflammation. Due to the advantages of short detection time and high sensitivity of cytokines, many studies have focused on relationship between cytokines and infection. However, few studies have been conducted on NHL patients with infection. Therefore, we reviewed the cytokine profiles of 229 newly diagnosed NHL patients and 40 healthy adults to predict respiratory bacterial infection and bacteremia. Our findings revealed that IL-6(41.67 vs 9.50 pg/mL), IL-8(15.55 vs 6.61 pg/mL), IL-10(8.02 vs 4.52 pg/mL),TNF-β(3.82 vs 2.96 pg/mL), IFN- γ(4.76 vs 2.96 pg/mL), body temperature(37.6 vs 36.5°C), CRP(20.80 vs 4.37 mg/L), and PCT(0.10 vs 0.04 ng/mL) levels were considerably greater in NHL cases with respiratory bacterial infections relative to NHL cases without infection (P

Introduction Infant jaundice is a common condition which results from a high concentration of serum bilirubin. Phototherapy is a widely used treatment for bilirubin clearance. We analyzed the effect of phototherapy on intestinal flora and metabolism of newborns. The aim was to assess the benefit of treatment for hyperbilirubinemia with phototherapy. Material and methods Fifty-three jaundiced infants hospitalized at our neonatal intensive care unit were treated with phototherapy. Of them, 29 were prescribed antibiotics during the hospitalization. Fecal samples were collected before and 24 h and 48 h after phototherapy. The bacterial species and relative abundance were identified with Macrogene sequencing. The bile acids in feces were identified using liquid chromatography-mass spectroscopy (LC-MS). Results Differential microbial species/genera and secondary bile acids were found after phototherapy. There are significant differences in the changes of the microbial species/genera between infants who did not receive antibiotic treatment and those who were given antibiotic treatment. Secondary bile acids were also significantly altered. At the same time, the differential microbial species/genera and the differential secondary bile acids interacted with each other. Conclusions This study identified several differential intestinal microbial species and secondary bile acids in fecal samples from infants with jaundice before and after phototherapy. Phototherapy can change the flora and its metabolism and its long-term impact needs further observation.

In order to reveal the multi-time scale of rainfall, runoff and sediment in the source area of the Yellow River and improve the accuracy of annual runoff forecast, the Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) method is introduced to decompose the measured rainfall, runoff and sediment data series of the Tangnahai hydrological station in the source area of the Yellow River of China. With the co-integration theory, two new error correction models (ECMs) for the forecast of annual runoff in the source area of the Yellow River are constructed. The application of these two methods solves the problem of pseudo-regression caused by nonlinearity and non-stationary of hydrological time series. The results show that rainfall, runoff and sediment in the source area of the Yellow River have multi-time scales and the component sequences have co-integration relationships. For two new ECMs, the CEEMDAN component ECM has better forecast accuracy than the original sequence one. The relative error of all forecasted values is less than 15% except 2009, and the accuracy has reached level A. HIGHLIGHTS The research on the multi-time scale change law of hydrological variables reveals the multi periodic change law of hydrological variables and provides a scientific basis for the rational development of water resources.; The non-stationary and nonlinear processing of hydrological variables can avoid spurious regression and make the result more accurate.; Study on the co-integration relationship of rainfall, runoff and sediment.; Study on multi-time scale dynamic relationship among rainfall, runoff and sediment.; Multi-time scale prediction of river runoff provides a technical reference for the effective protection and scientific operation of water resources.;

A novel high performance SiC asymmetric cell trench MOSFET with split gate (SG) and integrated junction barrier schottky (JBS) diode (SGS-ATMOS) is proposed for the first time. The shielding effect provided by the SG structure not only reduces the gate-drain capacitance ( ${C}_{\mathrm{gd}}$ ) but also alleviates the electric field crowding in the dielectric layer at trench corner. The integrated trench JBS diode bypasses the PiN body diode while obtaining good double protection from the SG and p-type shielding region. Therefore, not only the MOSFET but also diode performance is significantly improved for the proposed structure. Numerical analysis results show that compared with the conventional asymmetric cell trench MOSFET (Con-ATMOS), the high frequency figure of merit (HFFOM1, ${R}_{\mathrm{on}} {\cdot } {C}_{\mathrm{gd}}$ ) is reduced by 92.5% and the Baliga figure of merit (BFOM, ${BV}^{2}/R_{\mathrm{on,sp}}$ ) is increased by 57.2%, respectively. In addition, the forward conduction voltage drop ( ${V}_{\mathrm{F}}$ ), reverse recovery charge ( ${Q}_{\mathrm{rr}}$ ) and peak reverse recovery current ( ${I}_{\mathrm{rrm}}$ ) of the diode are reduced from 3.10V, $1.95\mu \text{C}$ /cm2 and 68.0A for the Con-ATMOS to 1.56V, $0.97\mu \text{C}$ /cm2 and 35.9A for the proposed SGS-ATMOS, respectively. Compared with the Con-ATMOS, the turn-on loss ( ${E}_{\mathrm{on}}$ ) and turn-off loss ( ${E}_{\mathrm{off}}$ ) of the proposed device are reduced by 33.3% and 33.0%, respectively. The ${E}_{\mathrm{on}}$ and ${E}_{\mathrm{off}}$ of the proposed device are also 33.6% and 30.0% off compared with the Con-ATMOS with external JBS diode, respectively. The temperature characteristics of the SGS-ATMOS are also discussed and it is found that the proposed device exhibits good performance at high temperature.

A novel carrier stored trench bipolar transistor (CSTBT) with split gate (SG) and recessed emitter trench (SGRET CSTBT) is proposed. The proposed device features a SG structure with thicker oxide layer under the trench gate and recessed trench emitter, respectively. Compared with the conventional CSTBT with recessed emitter trench (RET CSTBT), the proposed device not only significantly reduces the gate-collector capacitance ( ${C} _{\mathrm{ GC}}$ ) but also alleviates the negative impact of the heavily doped n-type carrier stored layer on the breakdown voltage (BV). Simulation results show that with the similar BV of about 650V, the on-state voltage drop ( ${V} _{\mathrm{ ceon}}$ ) at ${J} _{\mathrm{ ce}}$ =200A/cm2 for the proposed SGRET CSTBT is only 1.11V, which is 0.19V lower than that of the conventional RET CSTBT. Moreover, compared with the conventional RET CSTBT, the ${C} _{\mathrm{ GC}}$ at the ${V} _{\mathrm{ ce}}$ of 25V, total gate charge ( ${Q} _{\mathrm{ G}}$ ) and miller plateau charge ( ${Q} _{\mathrm{ GC}}$ ) for the proposed device are reduced by 84.3%, 38.6% and 51.6%, respectively. As a result, the trade-off relationship between the ${V} _{\mathrm{ ceon}}$ and turn-off loss ( ${E} _{\mathrm{ off}}$ ) as well as trade-off relationship between the turn-on loss ( ${E} _{\mathrm{ on}}$ ) and $\text{d}{V} _{\mathrm{ ak}} / \text{d}{t}$ of the free-wheeling diode (FWD) are significantly improved for the proposed device. At the same ${V} _{\mathrm{ ceon}}$ of 1.16V, the ${E} _{\mathrm{ off}}$ is reduced from 9.2mJ/cm2 of the conventional one to 3.3mJ/cm2 of the proposed device. At the same ${E} _{\mathrm{ on}}$ of 8.3mJ/cm2, the $\text{d}{V} _{\mathrm{ ak}} / \text{d}{t}$ of FWD for the proposed device is reduced by 24.5% compared with that of the conventional RET CSTBT, which significantly suppresses the EMI noise.

The aggregation pheromone of the brown marmorated stink bug, Halyomorpha halys (Stål), is produced by adult males, and plays an important role in the behavioral regulation of H. halys. However, information on the molecular mechanisms underlying this pheromone’s biosynthesis is limited. In this study, HhTPS1, a key candidate synthase gene in the aggregation pheromone biosynthesis pathway of H. halys, was identified. Then, through weighted gene co-expression network analysis, the candidate P450 enzyme genes in the biosynthetic downstream of this pheromone and the related candidate transcription factor in this pathway were also identified. In addition, two olfactory-related genes, HhCSP5 and HhOr85b, involved in the recognition of the aggregation pheromone of H. halys, were detected. We further identified the key amino acid sites of HhTPS1 and HhCSP5 that interact with substrates by using molecular docking analysis. This study provides basic information for further investigations into the biosynthesis pathways and recognition mechanisms of aggregation pheromones in H. halys. It also provides key candidate genes for bioengineering bioactive aggregation pheromones necessary for the development of technologies for the monitoring and control of H. halys.

Herbivore-induced plant volatiles (HIPVs) are released by plants upon damaged or disturbance by phytophagous insects. Plants emit HIPV signals not merely in reaction to tissue damage, but also in response to herbivore salivary secretions, oviposition, and excrement. Although certain volatile chemicals are retained in plant tissues and released rapidly upon damaged, others are synthesized de novo in response to herbivore feeding and emitted not only from damaged tissue but also from nearby by undamaged leaves. HIPVs can be used by predators and parasitoids to locate herbivores at different spatial scales. The HIPV-emitting spatial pattern is dynamic and heterogeneous in nature and influenced by the concentration, chemical makeup, breakdown of the emitted mixes and environmental elements (e.g., turbulence, wind and vegetation) which affect the foraging of biocontrol agents. In addition, sensory capability to detect volatiles and the physical ability to move towards the source were also different between natural enemy individuals. The impacts of HIPVs on arthropod natural enemies have been partially studied at spatial scales, that is why the functions of HIPVs is still subject under much debate. In this review, we summarized the current knowledge and loopholes regarding the role of HIPVs in tritrophic interactions at multiple scale levels. Therefore, we contend that closing these loopholes will make it much easier to use HIPVs for sustainable pest management in agriculture.

PurposeThe clinical significance of endovascular therapy in young patients with symptomatic intracranial atherosclerotic stenosis is not clear. We aimed to report our preliminary findings on the safety and effectiveness of a new endovascular treatment strategy, drug-coated balloon (DCB)-oriented angioplasty for young adults with severe symptomatic atherosclerotic middle cerebral artery (MCA) stenosis.MethodsWe retrospectively retrieved the data of seven young patients aged 21–32 years old with severe symptomatic atherosclerotic MCA stenosis treated with DCB-oriented angioplasty from January 2018 to October 2020. We collected clinical presentations, perioperative complications, and clinical and radiological outcomes.ResultsThe DCB was successfully dilated at the lesions in all seven patients and good antegrade perfusion was achieved in five. The other two patients underwent remedial stent implantation due to residual stenosis >50% and unstable antegrade perfusion after DCB dilatation. However, none of the patients had perioperative complications. There were no recurrent ischemic symptoms after a mean clinical follow-up period of 15.4 ± 6.9 months. Repeat vascular images of the patients showed no restenosis at 3- or 6-month imaging follow-up periods. High-resolution MRI (HRMRI) was completed in all the patients before the angioplasty procedure and at follow-up. Focal eccentric wall thickening was present at the site of stenosis preoperatively; however, the plaques had disappeared by the time of follow-up for all patients.ConclusionDCB-oriented angioplasty may be safe and effective for young patients with severe symptomatic atherosclerotic MCA stenosis.

BackgroundStudies on the recanalization for occlusion of the internal carotid artery terminus are scattered. Recently, drug-coated balloon (DCB) has been increasingly applied in the intracranial artery occlusion and achieved encouraging results. However, there seems no convincing data for the nonacute symptomatic internal carotid artery terminus occlusion (sICATO).ObjectiveTo assess the feasibility and effectiveness (safety) of DCB for patients with nonacute sICATO refractory to medical therapy.ApproachThis study included 30 patients with nonacute sICATO treated with DCBs and/or remedial stenting. The rate of successful recanalization, periprocedural complications, and clinical and vascular imaging follow-up outcomes were retrospectively analyzed.ResultsDrug-coated balloon (DCB) dilatation of nonacute sICATO gives a 100% rate of successful recanalization, with a low complication rate (10.00%), good clinical outcomes (86.20%), low restenosis/reocclusion rate (3.45%), and one asymptomatic ipsilateral infarction (3.45%).ConclusionDrug-coated balloon dilation seems to be the promising treatment option for nonacute sICATO considering its safety and feasibility.

Five Camellia oleifera Abel seedling substrates were prepared using the conventional formula, but with the peat substituted by the composts of Camellia oleifera shell, pine chips, palm fiber residues, chicken manure, and sheep manure. The physical and chemical properties of the prepared substrates before and after seedling cultivation were determined and their effects on the growth of Camellia oleifera seedling were analyzed. It was found that the survival rates of the one-year-old seedlings produced from stem cuttings on all substrates at 6 months were greater than 97.5%. As compared with the conventional substrate, the substrates formulated with the composts were able to promote the seedling growth based upon height, ground diameter, root length and root volume measurement. The substrate prepared with the compost of Camellia oleifera shell+ palm fiber residue+ chicken manure (A3), vermiculite and perlite (6:3:1) was the most optimal, which gave 100% seedling survival rate, the greatest seedling height, and the largest ground diameter. In particular, the ground diameters and 26.67% of the seedling heights reached the grade 1 standard for two-year-old seedlings.

Drug-resistant tuberculosis (TB) is a serious public health problem and threat to global TB prevention and control. Streptomycin (STR) is the earliest and classical anti-TB drug, and it is the earliest drug that generated resistance to anti-TB treatment, which limits its use in treating TB and impedes TB control efforts. The rapid, economical, and highly sensitive detection of STR-resistant TB may help reduce disease transmission and morbimortality. CRISPR/CRISPR-associated protein (Cas) is a new-generation pathogen detection method that can detect single-nucleotide polymorphisms with high sensitivity and good specificity. In this study, a Cas12a RR detection system that can recognize more non-traditional protospacer-adjacent motif-targeting sequences was developed based on Cas12a combined with recombinase polymerase amplification technology. This system detects 0.1% of the target substance, and the entire detection process can be completed within 60 min. Its sensitivity and specificity for detecting clinical STR-resistant Mycobacterium tuberculosis were both 100%. Overall, the Cas12 RR detection system provides a novel alternative for the rapid, simple, sensitive, and specific detection of STR-resistant TB, which may contribute to the prompt treatment and prevention of disease transmission in STR-resistant TB.

Mitochondria, as one of the most critical subcellular organelles of cancer cells, are very vulnerable and often on the verge of oxidative stress. The classic chemodynamic therapy (CDT) directly employs endogenous chemical energy to trigger reactive oxygen species (ROS) burst and destroy tumor cells. However, the effectiveness of CDT is restricted by the limited diffusion distance and short half-life of ROS. From this perspective, the treatment method (mitochondria-targeting chemodynamic therapy nanodrugs, M-CDT nanodrugs) that can generate high levels of ROS at the mitochondrial site is extremely efficient and promising for cancer treatment. Currently, many emerging M-CDT nanodrugs have been demonstrated excellent spatial specificity and anti-cancer efficacy. In this minireview, we review various proof-of-concept researches based on different M-CDT nanodrugs designs to overcome the limits of the efficacy of CDT, mainly divided into four strategies: supplying H2O2, non-H2O2 dependent CDT, eliminating GSH and enhancing by hyperthermia therapy (HT). These well-designed M-CDT nanodrugs greatly increase the efficacy of CDT. Finally, the progress and potential of M-CDT nanodrugs are discussed, as well as their limitations and opportunities.

Mental health is a major public health issue that affects social development. This study aims to explore the psychological state of residents of Hainan Island and its influencing factors during the COVID-19 pandemic and to provide a scientific basis for the formulation of psychological counseling measures to be used after the pandemic. We used the nonprobability snowball sampling method to conduct an online survey from February 21 to February 28, 2020, and collected a sample of 533 respondents. Using a binary logistic regression model and network analysis, the psychological state of residents and the main factors were analyzed during the concentrated outbreak of COVID-19 (from January 20 to February 16, 2020). The study found that during the pandemic, 92.7% of the respondents were in a poor state of mind, and 54.2% experienced severe psychological stress. The mental state is spatially expressed as a pattern of "high in the middle and low in the surroundings." Second, within the four-week sample, the overall psychological tension showed an inverted U-shaped trend. Respondents feeling stressed were most common in the second week, when they accounted for 87.99% of the total. Third, individual characteristics such as gender, age, fixed expenditure, and family size significantly affect the mental state. Women, the elderly, residents with fixed expenditures, and residents with large families are at greater risk of psychological stress. Finally, external factors such as the distance between residents and the location of cases and the node degree of the pandemic transmission network have a significant impact on the psychological state. However, residents in the least developed areas of Hainan Island, which are far away from active cases and have a low node degree, are more prone to psychological pressure. The government needs to pay special attention to these groups when constructing a long-term mechanism of psychological crisis intervention and increase public health resource investment in underdeveloped areas.

Compressive sensing (CS) is an effective technique that can compress and recover sparse signals below the Nyquist-Shannon sampling theorem restriction. In this study, we successfully realize CS based on the mesoscopic chaos of an integrated Si optomechanical photonic crystal micro-cavity, which is fully compatible with the complementary metal-oxide-semiconductor (CMOS) process. Using the sensing matrix, we tested one-dimensional waveforms and two-dimensional images. The ultimate recovery curves were determined by comparing the chaotic sensing matrix with the Gaussian, Toeplitz, and Bernoulli matrices. Our results could pave the way for future large-scale implementations of high-speed CS processes based on fully CMOS-compatible Si-micro-cavities.

Adult patients with hematological malignancies are frequently accompanied by bacterial infections in the lungs when they are first diagnosed. Sputum culture, procalcitonin (PCT), C-reactive protein (CRP), body temperature, and other routinely used assays are not always reliable. Cytokines are frequently abnormally produced in adult hematological malignancies associated with a lung infection, it is uncertain if cytokines can predict lung bacterial infections in individuals with hematological malignancies. Therefore, we reviewed 541 adult patients newly diagnosed with hematological malignancies, of which 254 patients had lung bacterial infections and 287 patients had no other clearly diagnosed infections. To explore the predictive value of cytokines for pulmonary bacterial infection in adult patients with hematological malignancies. Our results show that IL-4, IL-6, IL-8, IL-10, IL-12P70, IL-1β, IL-2, IFN-γ, TNF-α, TNF-β and IL-17A are in the lungs The expression level of bacterially infected individuals was higher than that of patients without any infections (P

The development and utilization of 3p-block based MOFs as fluorescent materials has attracted significant attention in recent years. Herein, we have successfully constructed a versatile luminescent Ga-MOF (SNNU-63) with a 3d10 configuration and a large ligand twist configuration. Interestingly, the as-synthesized Ga-MOF exhibits excellent luminescence property and a good material for blue light-emitting diode (LED). At 80 K, this Ga-MOF shows multi-emission centers at 381, 462, and 494 nm. As a ratiometric thermometer, this Ga-MOF exhibits an excellent temperature sensing property with high relative sensitivity (Sm = 2.60 % K−1 at 110 K). The fluorescence intensity ratio I381/I494 shows a very good fit for the Boltzmann results (80–240 K). Moreover, the luminescent Ga-MOF exhibits an excellent selective detection of Fe3+ over other metal ions in aqueous an medium, and the limit of detection (LOD) towards Fe3+ ions is calculated to be 1.227 × 10−4 M. This work presents a versatile luminescent Ga-MOF material as a blue LED and fluorescent probe for low-temperature and selective Fe3+ sensing.

Dendritic cells (DCs) are composed of multiple lineages of hematopoietic cells and orchestrate immune responses upon detecting the danger and inflammatory signals associated with pathogen and damaged tissues. Under steady-state, DCs are maintained at limited numbers and the functionally quiescent status. While it is known that a fine balance in the DC homeostasis and activation status is also important to prevent autoimmune diseases and hyperinflammation, mechanisms that control DC development and activation under stead-state remain not fully understood. Here we show that DC-specific ablation of CBL and CBL-B (CBL-/-CBL-B-/-) leads to spontaneous liver inflammation and fibrosis and early death of the mice. The mutant mice have a marked expansion of classic CD8α+/CD103+ DCs (cDC1s) in peripheral lymphoid organs and the liver. These DCs exhibit atypical activation phenotypes characterized by an increased production of inflammatory cytokines and chemokines but not the cell surface MHC-II and costimulatory ligands. While the mutant mice also have massive T cell activation, lymphocytes are not required for the disease development. The CBL-/-CBL-B-/- mutation enhances FLT3-mTOR signaling, due to defective FLT3 ubiquitination and degradation. Blockade of FLT3-mTOR signaling normalizes the homeostasis of cDC1s and attenuates liver inflammation. Our result thus reveals a critical role of CBLs in the maintenance of DC homeostasis and immune quiescence. This regulation could be relevant to liver inflammatory diseases and fibrosis in humans.

An ultra-compact multimode wavelength demultiplexer (MWD) with a footprint of 3.6 × 2.4 μm2 was designed. Its size is approximately two orders of magnitude smaller than the size of the traditional waveguide-based device. Moreover, the designed demultiplexer is multifunctional, and can realize wavelength demultiplexing and mode conversion at the same time. This MWD splits light at the wavelengths of 1450 nm and 1550 nm and simultaneously converts the input light from the fundamental transverse electric (TE0) mode to the first-order transverse electric (TE1) mode. The direct binary search (DBS) algorithm was employed to simulate the design. The results show that the insertion loss of the demultiplexer is −1.26 dB and −0.82 dB for the upper channel (wavelength 1450 nm) and lower channel (wavelength 1550 nm), while the crosstalk values are maintained as low as −18.10 dB and −23.35 dB, respectively. Additionally, a similar structure can be expanded to several modes. Based on these advantages, this multifunctional photonics device is expected to be used extensively in advanced photonic integration circuits.

Background: Due to the novel coronavirus epidemic, medical workers are under immense psychological pressure. As such, the East Campus of Shanghai Sixth People's Hospital actively adopted the Symptoms Checklist 90 (SCL-90) to evaluate the mental health of hospital staff before and after the psychological intervention from the Employee Assistance Program (EAP).Methods: Medical workers from the East Campus of Shanghai Sixth People's Hospital were recruited for this study. Psychological evaluations were conducted using the SCL-90, with a score of >160 regarded as a positive result, or in other words, an indication of abnormal psychological symptoms. The EAP adopted different forms of psychological interventions for healthcare professionals, and participation in these measures was entirely voluntary. Medical workers completed the SCL-90 again after participating in the psychological intervention, and we analyzed the changes between their two assessments.Results: Of the 1,198 total medical staff present at the hospital, 844 participated in the initial survey, while only 652 completed the survey a second time (i.e., post-psychological intervention). Multivariate logistic regression analysis found that the psychological status of hospital staff was correlated with gender, education background, and fertility status (P < 0.05). The results showed that, compared with women, men's mental health status was better, with an OR value of 0.598 (0.372–0.962). Groups with high school, junior high school, and below education levels were at higher risk of psychological problems, with OR values of 23.655 (2.815–198.784) and 9.09 (2.601–31.801), respectively. Administrative occupations and having two or more children were protective factors for mental health, and the OR values were 0.400 (0.175–0.912) and 0.327 (0.152–0.703), respectively.Following the psychological intervention, we found that the mental health of hospital workers improved, as indicated by their second SCL-90 evaluations, although the proportion of medical staff willing to participate in the second evaluation was lower than the initial assessment. There were differences in the SCL-90 scores among different occupations, and there were also differences in the scores of employees of different occupations who had participated in the two evaluations. The employees of different positions who participated in the two evaluations were matched and analyzed and found that the depression and anxiety of the doctor group were significantly reduced. In the nursing group, the total score, somatization, interpersonal sensitivity, depression, and anxiety were significantly reduced. In the medical technician group, depression, anxiety, and paranoia were reduced considerably. Among office staff, no significant differences were found. Among workers, the total score, depression, and anxiety were significantly reduced.Conclusion: Hospitals have the potential to alleviate and reduce the psychological pressure placed on medical staff members through the EAP, which can actively adopt intervention and guidance measures. The findings of this study have important implications, as reducing abnormal psychological symptoms of healthcare professionals can be helpful in the fight against the coronavirus epidemic.

Risk management is very important for individual investors or companies. There are several ways to measure the risk of investment. Prices of risky assets vary rapidly and randomly due to the complexity of finance market. Random interval is a good tool to describe uncertainty including both randomness and imprecision. Considering the uncertainty of financial market, we employ random intervals to describe returns of a risk asset and define an interval-valued risk measurement, which considers the tail risk. It is called the interval-valued conditional value-at-risk (ICVaR, for short). Similar to the classical conditional value-at-risk, ICVaR satisfies the sub-additivity. Under the new risk measure ICVaR, as a manner similar to the classical Mean-CVaR portfolio model, two optimal interval-valued portfolio selection models are built. The sub-additivity of ICVaR guarantees the global optimal solution to the Mean-ICVaR portfolio model. Based on the real data from mainland Chinese stock markets and international stock markets, the case study shows that our models are interpretable and consistent with the practical scenarios.

The sprinkler irrigation method has been widely used in agricultural fields due to its high water productivity and microclimate regulation traits. Quantitative analysis of the water distribution of sprinkler irrigation water by considering canopy influence is critical to evaluate crop growth and water use efficiency. In this study, stemflow was measured by collecting the water flowing down along stems using a high-adsorption sheet, throughfall water was measured by contains placed between wheat rows, and canopy interception was measured by the mass difference of plants between before and after sprinkler irrigation during wheat anthesis and grain-filling stages in the North China Plain. The results showed that the canopy interception water was between 0.6 and 1.3 mm, with a mean of 0.9 mm per sprinkler irrigation event for a leaf area index of approximately 4. Stemflow water was linearly related to the irrigation water and approximately 30% of the irrigation water. The throughfall water was also linearly related to the irrigation water above the canopy and accounted for approximately 60% of the irrigation water. The three components of sprinkler water are weakly influenced by the plant leaf area index, wind conditions and sprinkler irrigation system layouts in this study.

In recent years, metasurfaces have demonstrated a tremendous development potential and applicability in various fields as they have overcome the problems associated with traditional optical devices, including bulkiness and difficulties related to integration. The vortex beam can carry an unlimited amount of orbital angular momentum which can greatly increase the capacity of the communication system and thus attain a tremendous applicability potential in communication and information transmission. In this study, a vortex-focused beam metalens array is designed based on computer-generated holography technology for use in the visible light range. The antenna’s unit structure is arranged according to the phase distribution designed using computer-generated holography technology. The metalens array can convert circularly polarized light into a vortex beam and can focus the vortex beam. At the wavelengths of 420 nm, 550 nm, and 660 nm, the average conversion efficiency exceeds 80%, and the phase distribution is in the range of 0–2π. The metalens array can simultaneously generate and focus the vortex beams. We also studied the focusing effect of different vortex beams, and we analyzed and compared the focal length and full width at half maximum of metalens at different wavelengths and different topological charges. In addition, the focusing of the primary color light by the 3 × 3 metalens array is simulated. The design presented in this study is envisaged to be applied extensively in the fields of optical photography and optical communication systems.

Background The discovery of checkpoint inhibitors towards cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has been revolutionary for the treatment of cancers. These therapies have only offered an average of 20%–30% response rates across the tumor spectrum and the combination of agonists towards the tumor-necrosis superfamily members, such as 4-1BB and CD40, has shown potent efficacy in preclinical studies; however, these agonists have exhibited high degrees of toxicity with limited efficacy in human trials. In this study, we have generated a single-domain antibody towards a unique epitope of 4-1BB that limits its potential on-target toxicity while maintaining sufficient potency. This 4-1BB binder is ideal for use in the engineering of multispecific antibodies to localize 4-1BB activation within the tumor microenvironment, as shown here by a anti-PD-L1/4-1BB bispecific candidate (PM1003).Methods To determine the functional activity of the 4-1BB- and PD-L1-binding elements of PM1003, in vitro luciferase reporter and primary cell assays were used to test the potency of programmed cell death 1 ligand 1 (PD-L1) blockade and PD-L1-mediated 4-1BB activation via cross-bridging. X-ray crystallography was conducted to resolve the binding epitopes of the respective binding arms, and accurate binding kinetics were determined using standard affinity measurement techniques. Human 4-1BB and/or PD-L1 knock-in mice were used in cancer models for testing the in vivo antitumor efficacy of PM1003, and safety was evaluated further.Results PM1003 shows potent activation of 4-1BB and blockade of PD-L1 in cell-based assays. 4-1BB activation was exerted through the bridging of PD-L1 on target cells and 4-1BB on effector cells. No PD-L1-independent activation of 4-1BB was observed. Through X-ray crystallography, a unique binding epitope in the cysteine-rich domain 4 (CRD4) region was resolved that provides high potency and potentially low on-target toxicity as determined by primary immune cell assays and toxicity evaluation in vivo.Conclusions A unique single-domain antibody was discovered that binds to the CRD4 domain of 4-1BB. When incorporated into a 4-1BB/PD-L1 bispecific (PM1003), we have shown the potent inhibition of PD-L1 activity with 4-1BB agonism upon cross-bridging with PD-L1 in vitro. Antitumor activity with minimal toxicity was found in vivo. Thus, PM1003 is a uniquely differentiating and next generation therapeutic agent for cancer therapy.

Honey produced from medicinal plants holds great promise for human health. Increasing evidence suggests that the gut microbiota plays an important role in liver pathology after alcohol intake. The aim of this study was to identify the polyphenol composition of triadica cochinchinensis honey (TCH), and to study the potential effect of honey polyphenols on the regulation of gut microbes in mice with alcohol-induced liver injury and the improvement of alcohol-induced liver disease. For these purposes, a total of 190 compounds were identified and 27 of them were quantified by ultraperformance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and we successfully established a mouse model of alcohol-induced liver injury. The results show that TCH polyphenols can significantly restore the levels of ALT and AST, and TCH intervention can significantly improve the pathological changes of liver tissue in alcohol-exposed mice. Additionally, a significant decrease was observed in Firmicutes/Bacteroidetes after TCH treatment. Moreover, KEGG pathways of ATP-binding cassette (ABC) transporters, two-component system and biosynthesis of amino acids enriched the most differentially expressed genes after TCH intervention for 8 weeks. Our results may have important implications for the use of TCH as a functional food component with potential therapeutic utility against alcohol-induced liver disease.

Abstract Background A carbapenem-resistant hypermucoviscous Klebsiella pneumoniae isolate was recovered from human sputum. Methods Whole genome sequencing of this isolate was carried out to reveal its clonal background, antimicrobial resistance determinants and virulence factors. Virulence assays were performed using wax moth larvae. The transfer of bla NDM-5 between bacterial strains was tested using conjugation. 59 genome assemblies of ST29 K. pneumoniae and 230 IncX3 plasmids regardless of the carriage of resistance gene were employed for phylogenetic analysis, respectively. Results The strain carried a virulence plasmid pVir-SCNJ1 bearing the virulence gene rmpA and exhibited a high virulence in wax moth. This hypervirulent strain belongs to sequence type 29 and carries bla NDM-5, which is located on a conjugative plasmid, designated pNDM5-SCNJ1, belonging to type IncX3. pNDM5-SCNJ1 was fully sequenced and shows high similarity with pNDM_MGR194, except some deletion inside the ISAba125 region. Phylogenetic analysis of IncX3 plasmids revealed that although bla NDM-5 can be evolved from bla NDM-1 via point mutations within some IncX3 plasmids, most of bla NDM-5-carrying IncX3 plasmids probably have acquired bla NDM-5 in multiple events. Conclusions In this study, we characterized a bla NDM-5-positive hypervirulent K. pneumoniae of sequence type 29 in China. Our results highlight the need for active surveillance on this lineage of carbapenem-resistant K. pneumoniae.

Abstract Background Contrast-induced encephalopathy (CIE) is a well-known complication of iodinated contrast agents during angiography and vascular interventions. It can manifest as hemiparesis, cortical blindness, speech changes, Parkinsonism, confusion, seizure, and coma. Most of the reported CIE cases have been transient and reversible. Irreversible fatal CIE cases have been rarely reported. All the fatal CIE cases reported involved the use of ionic high osmolar contrast agents. Here, we document a heretofore unreported fatal CIE after digital subtraction angiography (DSA) using iopamidol, which is a type of non-ionic monomer low osmolar contrast agent. Case presentation A 71-year-old woman was admitted to our Department of Neurology for tinnitus in the head. The cerebral magnetic resonance angiography (MRA) detected atherosclerotic cerebral arteries and bilateral stenosis of the middle cerebral arteries. The patient underwent DSA for further diagnostic work-up. The total amount of iopamidol used during the procedure was 110 ml. The patient experienced headache during the procedure, followed by dizziness with nausea and vomiting. Despite treatment with anti-oedema medications, her clinical status was gradually deteriorating and ended up with deep coma due to irreversible cerebral oedema which was confirmed by cerebral computed tomography (CT). Finally, the patient died 56 days after the procedure due to irreversible fatal cerebral oedema. Conclusions This report documents that iopamidol-induced encephalopathy may not always have a benign outcome and can result in irreversible fatal cerebral oedema.

Plants have evolved a number of different chemical defenses, covering nearly all classes of (secondary) metabolites, that represent a major barrier to herbivory: some are constitutive; others are induced after attacks from herbivores (HIPVs) and may elicit the attraction of predators and parasitoids. Here, we studied how the female solitary endoparasitoid Aphelinus varipes responds to plant and host aphid volatiles in a series of experiments on five commercially important vegetables that were either healthy or infested with the aphid Myzus persicae: chili pepper, eggplant, crown daisy, Chinese cabbage and cabbage. The results for the olfactory responses of A. varipes showed that the presence of M. persicae increased the attraction of the endoparasitoid to the infested plants. In a second experiment, volatiles from highly attractive and repellent plants were obtained via headspace collection to investigate volatiles from healthy and aphid-damaged plants. The results for the differences in volatile profiles in response to aphid infestation in chili pepper cultivar were dominated by the volatile blends, including α-pinene, decanal and phthalic acid, while in cabbage they were dominated by isophorone. Moreover, when HIPVs with different concentrations were compared, α-pinene at a dose rate of 100 ng/μL attracted more parasitoids, and the comparison was useful to understand the mechanisms of plant secondary volatiles during aphid infestation and to provide new resources to control this insect pest. Overall our study shows how HIPVs can bolster tritrophic interactions by enhancing the attractiveness of parasitoids.

Abstract Background Tumor-associated macrophages (TAMs) facilitate tumor progression via establishment of an immunosuppressive tumor microenvironment (TME). However, it is poorly understood how tumor cells could functionally modulate TAMs. Our previous work indicated that tumor cell-released autophagosomes (TRAPs), a type of LC3-II+ double-membrane extracellular vesicles (EVs) was sufficient to suppress anti-tumor immune responses by inducing IL-10-producing B cells and immune suppressive neutrophils. Here, we hypothesized that TRAPs may participate in regulating macrophage polarization. Methods TRAPs isolated from multiple murine tumor cell lines and pleural effusions or ascites of cancer patients were incubated with bone marrow-derived macrophages (BMDMs) and monocytes, respectively. Cellular phenotypes were examined by flow cytometry, ELISA and quantitative PCR. TRAPs treated BMDMs were tested for the ability to suppress T-cell proliferation in vitro, and for promotion of tumor growth in vivo. Transwell chamber and neutralization antibodies were added to ascertain the inhibitory molecules expressed on BMDMs exposed to TRAPs. Knockout mice were used to identify the receptors responsible for TRAPs-induced BMDMs polarization and the signaling mechanism was examined by western blot. Autophagy-deficient tumors were profiled for phenotypic changes of TAMs and IFN-γ secretion of T cells by flow cytometry. The phenotype of monocytes from pleural effusions or ascites of cancer patients was assessed by flow cytometry. Results TRAPs converted macrophages into an immunosuppressive M2-like phenotype characterized by the expression of PD-L1 and IL-10. These macrophages inhibited the proliferation of both CD4+ and CD8+ T cells in vitro, and promoted tumor growth mainly through PD-L1 in vivo. TRAPs-induced macrophage polarization was dependent on TLR4-mediated MyD88-p38-STAT3 signaling. In vivo studies indicated that disruption of autophagosome formation in B16F10 cells by silencing the autophagy gene Beclin1 resulted in a remarkable delay in tumor growth, which was associated with reduced autophagosome secretion, TAMs reprogramming and enhanced T cell activation. Moreover, the levels of LC3B+ EVs appeared to correlate significantly with up-regulation of PD-L1 and IL-10 in matched monocytes from effusions or ascites of cancer patients, and TRAPs isolated from these samples could also polarize monocytes to an M2-like phenotype with increased expression of PD-L1, CD163 and IL-10, decreased expression of HLA-DR, and T cell-suppressive function. Conclusions These findings suggest the TRAPs-PD-L1 axis as a major driver of immunosuppression in the TME by eliciting macrophage polarization towards an M2-like phenotype, and highlight the potential novel therapeutic approach of simultaneously targeting autophagy and PD-L1.

Prolonged neuroinflammation is a driving force for neurodegenerative disease, and agents against inflammatory responses are regarded as potential treatment strategies. Here we aimed to evaluate the prevention effects on gliosis by dexamethasone (DEX), an anti-inflammation drug. We used DEX to treat the nicastrin conditional knockout (cKO) mouse, a neurodegenerative mouse model. DEX (10 mg/kg) was given to 2.5-month-old nicastrin cKO mice, which have not started to display neurodegeneration and gliosis, for 2 months. Immunohistochemistry (IHC) and Western blotting techniques were used to detect changes in neuroinflammatory responses. We found that activation of glial fibrillary acidic protein (GFAP) positive or ionized calcium binding adapter molecule1 (Iba1) positive cells was not inhibited in nicastrin cKO mice treated with DEX as compared to those treated with saline. These data suggest that DEX does not prevent or ameliorate gliosis in a neurodegenerative mouse model when given prior to neuronal or synaptic loss.

Background and Objectives: Previous studies on symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion that was refractory to medical therapy are rare. We aimed to assess the clinical features, imaging characteristics, endovascular treatment feasibility and follow-up outcomes of patients with this condition.Methods: Data from consecutive patients who had symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion and underwent endovascular recanalization from February 2016 to April 2020 were retrospectively collected in our prospective database. Clinical, imaging, procedural, and follow-up data were collected and analyzed.Results: Thirty-one patients, predominantly males, were enrolled in this study. These patients presented with recurrent/progressive stroke in the posterior circulation despite aggressive medical therapy. Angiographic analysis revealed asymmetric vertebral arteries due to unilateral hypoplasia and intracranial vertebral artery total occlusions in the dominant vertebral arteries, which were characterized by long lesion length and high clot burden. Multiple infarctions and perfusion defects in the posterior circulation were demonstrated by diffusion-weighted imaging and arterial spin labeling, respectively. Successful endovascular recanalization was achieved in 87.1% of the patients. Over a median clinical follow-up duration of 11.0 months, 74.1% of patients with successful recanalization achieved favorable clinical outcomes (mRS score ≤2).Conclusion: Symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion attributable to hypoperfusion is characterized by recurrent/progressive ischemic events, dominant intracranial vertebral artery total occlusion, long lesion length, and high clot burden. Endovascular recanalization of the dominant intracranial vertebral artery occlusion appears to be a feasible treatment for these patients.

A series of reconfigurable compact photonic arbitrary power splitters are proposed based on the hybrid structure of silicon and Ge2Sb2Se4Te1 (GSST), which is a new kind of non-volatile optical phase change material (O-PCM) with low absorption. Our pixelated meta-hybrid has an extremely small photonic integrated circuit (PIC) footprint with a size comparable to that of the most advanced electronic integrated circuits (EICs). The power-split ratio can be reconfigured in a completely digital manner through the amorphous and crystalline switching of the GSST material, which only coated less than one-fifth of the pattern allocation area. The target power–split ratio between the output channels can be arbitrarily reconfigured digitally with high precision and in the valuable C-band (1530–1560 nm) based on the analysis of three-dimensional finite-difference time-domain. The 1 × 2, 1 × 3, and 1 × 4 splitting configurations were all investigated with a variety of power–split ratios for each case, and the corresponding true value tables of GSST distribution are given. These non-volatile hybrid photonic splitters offer the advantages of an extremely small footprint and non-volatile digital programmability, which are favorable to the truly optoelectronic fusion chip.

The samurai wasp, Trissolcus japonicus, is the predominant egg parasitoid of the brown marmorated stink bug, Halyomorpha halys, in its native range in China. (E)-2-Decenal is a major component of the alarm pheromone of H. halys, an important invasive insect pest with significant economic importance. T. japonicus can be strongly repelled by (E)-2-decenal, and thus its host location efficiency would be reduced in the field. Better understanding on the molecular basis of olfactory reception of this host alarm pheromone component by T. japonicus may provide opportunities to develop novel approaches to enhance biological control efficacy of the parasitoid against H. halys. We identified six Odorant Binding Proteins (OBPs) from T. japonicus by transcriptome sequencing, within which three classical OBPs were expressed in a heterologous expression system with E. coli, harvested, and then challenged with (E)-2-decenal in binding assay experiments. TjapOBP2 showed the highest binding ability to (E)-2-decenal, compared to TjapOBP1 and TjapOBP3. Our results unambiguously suggest that TjapOBP2 would play an important role in discriminating (E)-2-decenal and could be a possible target for further intervention in the parasitoid–host system.

The brown marmorated stink bug, Halyomorpha halys (Hemiptera: Pentatomidae), is a serious agricultural and urban pest that has become an invasive species in many parts of the world. Olfaction plays an indispensable role in regulating insect behaviors, such as host plant location, partners searching, and avoidance of predators. In this study, we sequenced and analyzed the antennal transcriptomes of both male and female adults of H. halys to better understand the olfactory mechanisms in this species. A total of 241 candidate chemosensory genes were identified, including 138 odorant receptors (ORs), 24 ionotropic receptors (IRs), 15 gustatory receptors (GRs), 44 odorant-binding proteins (OBPs), 17 chemosensory proteins (CSPs), and three sensory neuron membrane proteins (SNMPs). The results of semi-quantitative reverse transcription PCR (RT-PCR) assays showed that some HhalOBP and HhalCSP genes have tissue-specific and sex-biased expression patterns. Our results provide an insight into the molecular mechanisms of the olfactory system in H. halys and identify potential novel targets for pest control strategies.