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Abstract Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

Large-scale short carbon fibre-reinforced silicon carbide (Csf/SiC) ceramic matrix composites (CMCs) have important applications in the field of aerospace engineering. This study proposed the use of material extrusion based additive manufacturing to fabricate large-scale Csf/SiC CMC preforms. In this paper, we determined how the key material extrusion parameters, including solid loading, nozzle diameter and layer height impact the stability of the additively manufactured Csf/SiC CMCs. The solid loading significantly influenced the stability of the Csf/SiC CMCs, and the slurry with 50 vol.% solid loading was better for additive manufacturing. The layer height played a significant role in the void formation in CMCs. It was appropriate for structure retention to set the layer height as 60–75% of the nozzle diameter. The effect of angle from vertical on the stability of out-of-plane structure was also investigated. When the angle was over 40o, the out-of-plane structure additively manufactured without supports tended to collapse. Large-scale Csf/SiC CMC preforms with out-of-plane structures were finally successfully fabricated. This study is believed to provide some fundamental understanding for the fabrication of large-scale fibre-reinforced ceramic matrix composites.

Abstract Chemo-resistance hinders the therapeutic efficacy of temozolomide (TMZ) in treating glioblastoma multiforme (GBM). Recurrence of GBM even after combination of maximal tumor resection, concurrent radio-chemotherapy, and systemic TMZ applocation is inevitable and attributed to the high therapeutic resistance of glioma stem cells (GSCs), which can survive, evolve, and initiate tumor tissue remodeling, the underlying mechanisms of GSCs chemo-resistance, have not been fully elucidated up-to-now. Emerging evidence showed that METTL3-mediated N6-methyladenosine (m6A) modification contributed to the self-renew and radio-resistance in GSCs, however, its role on maintenance of TMZ resistance of GSCs has not been clarified and need further investigations. We found that the cell viability and half-maximal inhibitory concentration (IC50) of GSCs against TMZ significantly decreased after GSCs underwent serum-induced differentiation to adherent growth of tumor cells. Besides, METTL3 expression and total m6A modification declined dramatically in consistence with GSCs differentiation. Knockdown of METTL3 weakened self-renew, proliferation and TMZ IC50 of GSCs, whereas enhanced TMZ induced γH2AX level, indicating upregulation of double-strand DNA damage. We also found that mRNA stability of two critical DNA repair genes (MGMT and APNG) was regulated by METTL3-mediated m6A modification. In conclusion, we speculated that METTL3-mediated m6A modification of MGMT and APNG mRNAs played crucial roles on suppression of TMZ sensitivity of GSCs, which suggest a potential new therapeutic target of METTL3 against GBM.

Metabolism remodelling of macrophages in the glioblastoma microenvironment contributes to immunotherapeutic resistance. However, glioma stem cell (GSC)-initiated lipid metabolism remodelling of transformed macrophages (tMΦs) and its effect on the glioblastoma microenvironment have not been fully elucidated. Total cholesterol (TC) levels and lipid metabolism enzyme expression in macrophages in the GSC microenvironment were evaluated and found that the TC levels of tMΦs were increased, and the expression of the lipid metabolism enzymes calmodulin (CaM), apolipoprotein E (ApoE), and liver X receptor (LXR) was upregulated. Knockdown of HOXC-AS3 led to a decrease in the proliferation, colony formation, invasiveness, and tumorigenicity of tMΦs. Downregulation of CaM resulted in a decline in TC levels. HOXC-AS3 overexpression led to increases in both CaM expression levels and TC levels in tMΦs. RNA pull down and mass spectrometry experiments were conducted and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was screened as the HOXC-AS3 binding proteins related to lipid metabolism. RIP and RNA pull down assays verified that HOXC-AS3 can form a complex with hnRNPA1. Knockdown of hnRNPA1 downregulated CaM expression; however, downregulation of HOXC-AS3 did not affect hnRNPA1 expression.TMΦs underwent lipid metabolism remodelling induced by GSC via the HOXC-AS3/hnRNPA1/CaM pathway, which enhanced the protumor activities of tMΦs, and may serve as a potential metabolic intervening target to improve glioblastoma immunotherapy.

Summary: Generation of chimeric antigen receptor (CAR) T cells from pluripotent stem cells (PSCs) will enable advances in cancer immunotherapy. Understanding how CARs affect T cell differentiation from PSCs is important for this effort. The recently described artificial thymic organoid (ATO) system supports in vitro differentiation of PSCs to T cells. Unexpectedly, PSCs transduced with a CD19-targeted CAR resulted in diversion of T cell differentiation to the innate lymphoid cell 2 (ILC2) lineage in ATOs. T cells and ILC2s are closely related lymphoid lineages with shared developmental and transcriptional programs. Mechanistically, we show that antigen-independent CAR signaling during lymphoid development enriched for ILC2-primed precursors at the expense of T cell precursors. We applied this understanding to modulate CAR signaling strength through expression level, structure, and presentation of cognate antigen to demonstrate that the T cell-versus-ILC lineage decision can be rationally controlled in either direction, providing a framework for achieving CAR-T cell development from PSCs.

Background: Cinnamon is a spice used in cooking and in large quantities as a medical complement with hypoglycemic and lipid-lowering properties. The potential pharmacological mechanisms underlying cinnamon’s anti-diabetic properties and its active ingredients have not been adequately determined. The current meta-analysis aims to systematically review the potential pharmacological mechanisms underlying the hypoglycemic and hypolipidemic efficacy of cinnamon administration and summarize clinical recommendations of cinnamon and its active ingredients.Method: Relevant randomized clinical trials (RCTs) were identified through a literature search that spanned the years January 2005 to April 2022. Retrieve electronic databases including Web of Science, PubMed, Embase, Medline, and the Cochrane Library. To obtain standardized mean differences (SMDs), continuous outcomes were pooled and 95 percent confidence intervals (CIs) were provided. Categorical outcomes were aggregated to calculate relative risks (RRs) and were accompanied by 95% CIs. Heterogeneity was measured using the Cochrane Q-test and I2 statistics, with a p < 0.05 considered as substantial heterogeneity. If I2 was less than 50%, a fixed effect model was employed; otherwise, a random effect model was used. Subgroup analyses and sensitivity analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger’s test. The data were analyzed using revman (V.5.3) and stata (V.15) software packages.Results: These 16 RCTs included a total of 1,020 patients who were followed for a duration ranging from 40 days to 4 months. According to the current meta-analysis results, glycolipid levels in diabetic individuals who received cinnamon were significantly improved as compared to those who got placebo (All p < 0.05). An adverse effect was only detected in one patient.Conclusion: These findings imply that cinnamon has a significant influence on lipid and glucose metabolism regulation. An even more pronounced effect was observed in patients with HbA1c of 8%. The results of this study suggested that cinnamon may be utilized as hypoglycemic and lipid-lowering supplement in clinical settings with a guaranteed safety profile.Systematic Review Registration: [PROSPERO], identifier [CRD42022322735].

Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity, but the mechanistic basis for these outcomes is incompletely understood. Here, we identify two immune lineage-dependent consequences of PNP inactivation dictated by distinct gene interactions. During T cell development, PNP inactivation is synthetically lethal with downregulation of the dNTP triphosphohydrolase SAMHD1. This interaction requires deoxycytidine kinase activity and is antagonized by microenvironmental deoxycytidine. In B lymphocytes and macrophages, PNP regulates Toll-like receptor 7 signaling by controlling the levels of its (deoxy)guanosine nucleoside ligands. Overriding this regulatory mechanism promotes germinal center formation in the absence of exogenous antigen and accelerates disease in a mouse model of autoimmunity. This work reveals that one purine metabolism gene protects against immunodeficiency and autoimmunity via independent mechanisms operating in distinct immune lineages and identifies PNP as a potentially novel metabolic immune checkpoint.

Abstract Many studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

With the spread of the COVID-19 pandemic and the implementation of closure measures in 2020, population mobility and human activities have decreased, which has seriously impacted atmospheric quality. Huaibei City is an important coal and chemical production base in East China, which faces increasing environmental problems. The impact of anthropogenic activities on air quality in this area was investigated by comparing the COVID-19 lockdown in 2020 with the normal situation in 2021. Tropospheric NO2, HCHO and SO2 column densities were observed by ground-based multiple axis differential optical absorption spectroscopy (MAX-DOAS). In situ measurements for PM2.5, NO2, SO2 and O3 were also taken. The observation period was divided into four phases, the pre-lockdown period, phase 1 lockdown, phase 2 lockdown and the post-lockdown period. Ground-based MAX-DOAS results showed that tropospheric NO2, HCHO and SO2 column densities increased by 41, 14 and 14%, respectively, during phase 1 in 2021 vs. 2020. In situ results showed that NO2 and SO2 increased by 59 and 11%, respectively, during phase 1 in 2021 vs. 2020, but PM2.5 and O3 decreased by 15 and 17%, respectively. In the phase 2 period, due to the partial lifting of control measures, the concentration of pollutants did not significantly change. The weekly MAX-DOAS results showed that there was no obvious weekend effect of pollutants in the Huaibei area, and NO2, HCHO and SO2 had obvious diurnal variation characteristics. In addition, the relationship between the column densities and wind speed and direction in 2020 and 2021 was studied. The results showed that, in the absence of traffic control in 2021, elevated sources in the Eastern part of the city emitted large amounts of NO2. The observed ratios of HCHO to NO2 suggested that tropospheric ozone production involved NOX-limited scenarios. The correlation analysis between HCHO and different gases showed that HCHO mainly originated from primary emission sources related to SO2.

Direct-ink-writing (DIW)-based 3D-printing technology combined with the direct-foaming method provides a new strategy for the fabrication of porous materials. We herein report a novel method of preparing porous SiC ceramics using the DIW process and investigate their mechanical and wave absorption properties. We investigated the effects of nozzle diameter on the macroscopic shape and microstructure of the DIW SiC green bodies. Subsequently, the influences of the sintering temperature on the mechanical properties and electromagnetic (EM) wave absorption performance of the final porous SiC-sintered ceramics were also studied. The results showed that the nozzle diameter played an important role in maintaining the structure of the SiC green part. The printed products contained large amounts of closed pores with diameters of approximately 100–200 μm. As the sintering temperature increased, the porosity of porous SiC-sintered ceramics decreased while the compressive strength increased. The maximum open porosity and compressive strength were 65.4% and 7.9 MPa, respectively. The minimum reflection loss (RL) was −48.9 dB, and the maximum effective absorption bandwidth (EAB) value was 3.7 GHz. Notably, porous SiC ceramics after sintering at 1650 °C could meet the application requirements with a compressive strength of 7.9 MPa, a minimum RL of −27.1 dB, and an EAB value of 3.4 GHz. This study demonstrated the potential of direct foaming combined with DIW-based 3D printing to prepare porous SiC ceramics for high strength and excellent EM wave absorption applications.

Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.

Acquired chemoresistance is a major limiting factor in the clinical treatment of glioblastoma (GBM). However, the mechanism by which GBM acquires therapeutic resistance remains unclear. Here, we aimed to investigate whether METTL3-mediated N6-methyladenosine (m6A) modification contributes to the temozolomide (TMZ) resistance in GBM. We demonstrated that METTL3 METTL3-mediated m6A modification were significantly elevated in TMZ-resistant GBM cells. Functionally, METTL3 overexpression impaired the TMZ-sensitivity of GBM cells. In contrast, METTL3 silencing or DAA-mediated total methylation inhibition improved the sensitivity of TMZ-resistant GBM cells to TMZ in vitro and in vivo. Furthermore, we found that two critical DNA repair genes (MGMT and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved TMZ resistance in GBM cells. Collectively, METTL3 acts as a critical promoter of TMZ resistance in glioma and extends the current understanding of m6A related signaling, thereby providing new insights into the field of glioma treatment.

Recent studies have reported that cancer associated fibroblasts (CAFs) and glioma stem-like cells (GSCs) played active roles in glioma progression in tumor microenvironment (TME). Long non-coding RNAs (lncRNAs) have been found to be closely associated with glioma development in recent years, however, their molecular regulatory mechanisms on CAFs in GSCs remodeled TME kept largely unelucidated. Our study found that GSCs could induce malignant transformation of fibroblasts (t-FBs) based on dual-color fluorescence tracing orthotopic model. Associated with poor prognosis, Lnc HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) was highly expressed in high-grade gliomas and t-FBs. Depleting HOTAIRM1 inhibited the proliferation, invasion, migration, and even tumorigenicity of t-FB. Conversely, overexpression of HOTAIRM1 promoted malignancy phenotype of t-FB. Mechanistically, HOTAIRM1 directly bound with miR-133b-3p, and negatively regulated the latter. MiR-133b-3p partly decreased the promotion effect of HOTAIRM1 on t-FBs. Furthermore, transforming growth factor-β (TGFβ) was verified to be a direct target of miR-133b-3p. HOTAIRM1 can modulate TGFβ via competing with miR-133b-3p. Collectively, HOTAIRM1/miR-133b-3p/TGFβ axis was involved in modulating t-FBs malignancy in TME remodeled by GSCs, which had the potential to serve as a target against gliomas.

Summary: Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, and PDGFRβ), a subset of cells defined as CD146hiCD73hi expressed genes associated with the HSPC niche and supported the maintenance of functional HSPCs ex vivo, while CD146loCD73lo cells supported differentiation. Stromal support of HSPCs was contact dependent and mediated in part through high JAG1 expression and low WNT signaling. Molecular profiling revealed significant transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of functionally diverse types of mesenchyme from hPSCs opens potential avenues to model the HSPC niche and develop PSC-based therapies. : Crooks and colleagues demonstrated a previously underappreciated functional and molecular heterogeneity in mesenchyme generated from human pluripotent stem cells. Two mesenchymal subsets were distinguished by the reciprocal expression of CD146, CD73, and CD140a. CD146hiCD73hi mesenchyme supported self-renewing hematopoietic stem and progenitor cells (HSPCs), expressed markers of the HSPC niche, and shared a similar molecular signature with primary human adult pericytes. Keywords: pluripotent stem cell, mesenchyme, hematopoietic stem cell niche, pericyte biology, directed differentiation, mesoderm

Phase change memory (PCM) formed by Ge2Sb2Te5 (GST) on vertical carbon nanotube (CNT) filled contact plug is demonstrated in this paper. In order to achieve compatibility with the underlying process, the CNTs are synthesized using nickel catalyst at a low temperature. Reasonable contact characteristics between the CNTs and GST are achieved without material compatibility problem. Due to the small contact size of the CNT to the phase change material, a significant reduction in programming power is achieved compared to metal contact at the same via size. The temperature simulation result shows that the CNT filled via helps to reduce the programming area. The fabricated PCM on CNT filled via is able to endure more than 104 SET/RESET cycles without observable degradation.

Synthesis of the vertically aligned carbon nanotubes (CNTs) using complementary metal-oxide-semiconductor (CMOS)-compatible methods is essential to integrate the CNT contact and interconnect to nanoscale devices and ultra-dense integrated nanoelectronics. However, the synthesis of high-density CNT array at low-temperature remains a challenging task. The advances in the low-temperature synthesis of high-density vertical CNT structures using CMOS-compatible methods are reviewed. Primarily, recent works on theoretical simulations and experimental characterizations of CNT growth emphasized the critical roles of catalyst design in reducing synthesis temperature and increasing CNT density. In particular, the approach of using multilayer catalyst film to generate the alloyed catalyst nanoparticle was found competent to improve the active catalyst nanoparticle formation and reduce the CNT growth temperature. With the multilayer catalyst, CNT arrays were directly grown on metals, oxides, and 2D materials. Moreover, the relations among the catalyst film thickness, CNT diameter, and wall number were surveyed, which provided potential strategies to control the tube density and the wall density of synthesized CNT array.

From July 4 to 11, 2006 at Back Garden site (23°28’86”N; 113°02’91”E), nighttime nitrate radical (NO3) was measured with a long path differential optical absorption spectroscopy (DOAS) during an intensive field campaign in the Pearl River Delta of China. The NO3 concentration in polluted air masses varied from 3.6 to 82.5 ppt with an average level of 21.8 ± 1.8 ppt. NO3 at these levels can play a significant role in oxidation of volatile organic compounds (VOCs). The calculated production rate of nitrate radical ranged from 8 × 105 to 2.98 × 107 cm-3 s-1, while its lifetimes spanned from between just several seconds to 650 seconds, with an average of 89 seconds. N2O5 levels were calculated with the average of 620 ± 93 ppt during this campaign. The possible scavenging processes for the nitrate radical were obtained by using a statistical analysis of the correlation between NO3 and NO levels, NO3 concentration and its production rate, and the NO3 lifetime and NO2 levels, respectively. Results showed that the direct losses were of importance at Back Garden in summer Pearl River Delta, China.

Colitis is an inflammatory intestinal disease that lasts for a long time, has an unknown cause, and occurs repeatedly. It is usually accompanied by symptoms such as intestinal cell damage, intestinal immunity, and abnormal intestinal flora. Numerous studies have shown that dietary fiber, as a prebiotic, its metabolites can selectively improve the composition of the intestinal flora, which in turn improves the level of intestinal short-chain fatty acids, reduces the expression of inflammatory factors, and enhances the function of the intestinal immune barrier, thereby improving the inflammatory response of the organism. This anti-inflammatory effect of dietary fiber through its metabolites provides new research ideas to assist in the treatment of colitis. This paper outlines the pathogenesis of colitis, and the mechanism of interaction between dietary fiber and its metabolites with intestinal flora, inflammatory factors and immune cells, aiming to provide theoretical basis for the alleviation of colitis by dietary fiber and the development of functional foods.

Abstract Background Systemic lupus erythematosus (SLE) and Wilson’s disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. Case report We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. Conclusions SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.

To solve the problem that hawthorn wine tends to lose its color and quality during storage, this experiment established the simulation system, and three acids with strong co-color ability were selected from eight phenolic and organic acids. The effects of the three phenolic and organic acids on the simulated system (0~30 d) and fermented hawthorn wine (storage time 0~120 d) were evaluated comprehensively by using the CIELab color system, and determining the chromatic colors, polyphenols, anthocyanins, and flavonoids. The results showed that different phenolic acids and organic acids had different cochromatic effects. Different phenolic and organic acid treatments in the CIELab color system in the simulated system showed good effects on the L*, a*, b*, C*ab and hab as well as on the chromatic hue of the wine. The total phenolic content of the wine was increased by 18.00% and 20.88% for ferulic acid and vanillic acid treatment, respectively, compared to the control group. The content of anthocyanin in the simulated system treated with p-hydroxybenzoic acid and vanillic acid increased by 17.27% and 15.74%, respectively, compared with the control group. During storage of fermented hawthorn wine, para-hydroxybenzoic acid could significantly improve the chromaticity (P

Objective The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians’ awareness of and attention to this disease.Methods We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes.Results All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G).Conclusion Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.

Abstract Psoriasis is an immune-mediated inflammatory skin disease, involving a complex interplay between genetic and environmental factors. Previous studies have demonstrated that genetic factors play a major role in the pathogenesis of psoriasis. However, non-genetic factors are also necessary to trigger the onset and recurrence of psoriasis in genetically predisposed individuals, which include infections, microbiota dysbiosis of the skin and gut, dysregulated lipid metabolism, dysregulated sex hormones, and mental illness. Psoriasis can also be induced by other environmental triggers, such as skin trauma, unhealthy lifestyles, and medications. Understanding how these triggers play a role in the onset and recurrence of psoriasis provides insights into psoriasis pathogenesis, as well as better clinical administration. In this review, we summarize the triggers for the onset and recurrence of psoriasis and update the current evidence on the underlying mechanism of how these factors elicit the disease. Video Abstract

Abstract Background Joubert syndrome (JS) is a rare genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the “molar tooth sign”, and variable organ involvement (such as eye, kidney, liver, and skeleton). Here, we present a case of JS in a Chinese boy. Case presentation An 11-year-old Chinese boy presented with neonatal asphyxiation and hypoxia, strabismus, subsequent developmental delay, ataxia and end-stage kidney disease (ESKD). Routine blood tests showed severe anemia, increasing blood urea nitrogen and creatinine, elevated parathyroid hormone, hypocalcemia, hypokalemia and metabolic acidosis. Urine tests showed mild proteinuria. Ultrasound showed two small kidneys. Brain magnetic resonance imaging (MRI) showed dysplasia of the cerebellar vermis and extension of the upper cerebellar feet with the “molar tooth sign”. Genetic analysis showed novel compound heterozygous mutations in the RPGRIP1L gene [p.L447fs*7(p.Leu447fsTer7) and p.G908V (p.Gly908Val)]. Conclusion In the present study, we identified novel compound heterozygous mutations in the RPGRIP1L gene in a Chinese boy. The clinical and genetic findings of this study will expand the understanding of JS.

Dietary fiber can be fermented and utilized by gut microbiota to reshape the gut microbiota, thereby alleviating constipation. This experiment mainly studied the physicochemical functions of hawthorn soluble dietary fiber (HSDF)and its effect and mechanism in alleviating constipation in mice. Forty-five mice were divided into blank control group C, model group M, positive control HS group, low-dose LHSDF group (1 g/kg/bw), and high-dose HHSDF group (2 g/kg/bw). The mice were modeled at a dose of 10 mg/kg/bw of loperamide hydrochloride for 7 days, while the remaining groups were orally administered an equal amount of distilled water and test samples. After continuous gavage for 45 days we performed a bowel movement test, and then continued gavage for 7 days and performed a small intestine propulsion test and indicator testing. The results showed that HSDF is mainly composed of galacturonic acid, belonging to the type I crystal structure, with a loose surface resembling a snowflake, a small molecular weight, and strong water-holding and antioxidant abilities. Animal experiments showed that compared with group M, HSDF significantly upregulated AQP3 and AQP8 by 52.67% and 164.54%, respectively, and downregulated AQP9 protein expression by 45.88%, thereby promoting intestinal peristalsis. It can also alleviate constipation by increasing the levels of excitatory hormones such as MTL, GAS, and SP in the gastrointestinal tract, and reducing the levels of inhibitory hormones such as SS, NO, and MDA. In addition, HSDF can reduce the levels of inflammatory factors such as IL-6 and PL-1 β, increase the content of various short-chain fatty acids, alleviate intestinal inflammation, maintain intestinal integrity, and promote defecation. It can also promote the growth of probiotics such as Bacteroides, inhibit the growth of harmful bacteria such as Bifidobacterium and Lactobacillus, and alter the diversity of gut microbiota.

Abstract Peripheral T-cell lymphomas (PTCLs) are a group of highly aggressive malignancies with generally poor prognoses, and the first-line chemotherapy of PTCL has limited efficacy. Currently, several novel targeted agents, including histone deacetylase inhibitors (HDACis), have been investigated to improve the therapeutic outcome of PTCLs. Several HDACis, such as romidepsin, belinostat, and chidamide, have demonstrated favorable clinical efficacy and safety in PTCLs. More novel HDACis and new combination therapies are undergoing preclinical or clinical trials. Mutation analysis based on next-generation sequencing may advance our understanding of the correlation between epigenetic mutation profiles and relevant targeted therapies. Multitargeted HDACis and HDACi-based prodrugs hold promising futures and offer further directions for drug design.

The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells. In this study, SD rats were divided into the normal chow diet group (NCD), high fat diet group (HFD), three treatment groups feeding high-fat diet with naringenin (100, 200, 400 mg/kg) for 12 weeks. Results indicated that naringenin treatment decreased total cholesterol (TC), triglyceride (TG) and the non-high-density lipoprotein cholesterol (non-HDL-C) levels in serum. Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats. In addition, naringenin (25−75 µg/mL) decrease TG and TC levels in 3T3 mature adipocytes. The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology. Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes. Meanwhile, naringenin increased the AMPK (AMP-activated protein kinase) activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes. And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C. Molecular docking results indicated that naringenin could bind to AMPK protein. These results indicated naringenin reduced lipid accumulation through AMPK pathway.

Abstract In this study, we investigated the nephroprotective effects of Umbelliferone (UMB) against cisplatin‐induced acute kidney injury (AKI). C57BL/6J mice were treated with cisplatin via a single intraperitoneal injection (25 mg/kg) with or without UMB (40 mg/kg/day) by gavage. Renal function, apoptosis, oxidative stress, inflammation, and mitochondrial function were analyzed to evaluate kidney injury. In vitro, human proximal tubule epithelial cells were treated with cisplatin, with or without UMB, for 24 h. Western blotting and immunohistochemistry were performed to explore the mechanisms underlying the nephroprotective effects of UMB. Cisplatin‐induced renal dysfunction, including increases in blood urea nitrogen, serum creatinine, and renal tubular injury indices (NGAL and KIM‐1), were significantly attenuated by UMB treatment, along with renal phenotypic changes and renal tubular injury, as evidenced by improved renal histology. Moreover, NRF2 was activated by UMB pretreatment, along with the inhibition of oxidative stress and inflammatory response, as evidenced by decreased levels of antioxidant genes and inflammatory cytokines in cisplatin‐induced AKI. Our results demonstrate that UMB can protect against cisplatin‐induced nephrotoxicity, which is mediated by the NRF2 signaling pathway via antioxidant and anti‐inflammatory activities, suggesting the clinical potential of UMB for the treatment of AKI.

Kidney injury leads to fibrosis during the progression of chronic kidney disease. Here the authors report that the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in a study with male mice, potentially via TAF7/RAPTOR/mTORC1 signaling.

Summary: Smart wearable sensors are electronic devices worn on the body that collect, process, and transmit various physiological data. Compared to traditional devices, their advantages in terms of portability and comfort have made them increasingly important in the medical field. This review takes a unique clinical physician’s standpoint, diverging from conventional sensor-type-based classifications, and provides a comprehensive overview of the diverse clinical applications of wearable sensors in recent years. In this review, we categorize these applications according to different diseases, encompassing skin diseases and injuries, cardiovascular diseases, abnormal human motion, as well as endocrine and metabolic disorders. Additionally, we discuss the challenges and perspectives hindering the development of sensors for clinical use, emphasizing the critical need for interdisciplinary collaboration between medical and engineering professionals. Overall, this review would serve as an important reference for the future direction of sensor devices in clinical use.

In order to improve the stability and bioavailability, hawthorn polyphenols microcapsules were prepared by spray drying using β-cyclodextrin. Whey protein isolate and gum Arabic as concentrations wall materials, and hawthorn polyphenols as the core material. The particle size, microscopic appearance, stability, sustained release and antioxidant properties of the microcapsules were analyzed. The results showed that core-to-wall-material ratio was 1:3 (v/v), air inlet temperature was 165 ℃ and emulsification time was 11.4 min as the optimum preparation process. Under all conditions optimized, the encapsulation rate was 94.45%±1.03% and the drug loading was 17.99%±0.20% of hawthorn polyphenol microcapsules, which average particle size was 6.77 μm, the microcapsules gained complete particles and spherical structure. The microcapsules showed well stability in gastric juice and well release performance in intestinal juice. The release rates of hawthorn polyphenols and hawthorn polyphenol microcapsules after 2 h of simulated gastric juice digestion were 13.38% and 9.75%, respectively, and 6 h after intestinal juice digestion were 95.99% and 72.53%, respectively. The oxidations resistance and stabilities were improved obviously after encapsulation. The IC50 values of hawthorn polyphenols for DPPH, OH, O2− free radical scavenging rates were 12.669 μg/mL and 1.131, 0.581 mg/mL, respectively, and the hawthorn polyphenol microcapsules were 0.939 μg/mL and 0.129, 0.546 mg/mL, respectively. After 10 days of light exposure, the retention rates of hawthorn polyphenols and hawthorn polyphenols microcapsules were 64.99% and 86.74%, respectively. The retention rates at 80°C were 70.77% and 88.77%, respectively, and the retention rates of hawthorn polyphenols and hawthorn polyphenols microcapsules stored without packaging for 28 days were 73.48% and 91.15%, respectively. These above results indicated that microcapsule technology could improve the stability, sustained release and antioxidant activities of hawthorn polyphenols, and could be used as an effective method to improve the processing stability of hawthorn polyphenols.

Objective To explore the clinical characteristics, treatment protocol and prognosis of children with anti-complement factor H (CFH) autoantibody (Ab)-associated hemolytic uremic syndrome (HUS).Methods Clinical data of 8 patients with anti-CFH Ab-associated HUS who were admitted to Shandong Provincial Hospital from January 2011 to December 2020 were collected retrospectively.Results The age at disease onset ranged between 5.83 and 13.5 years, with a male: female ratio of 1.67:1. The time of onset was distributed from May to June and November to December. Digestive and upper respiratory tract infections were common prodromal infections. Positivity for anti-CFH Ab and reduced C3 levels were observed among all patients. Heterozygous mutation of the CHFR5 gene (c.669del A) and homozygous loss of the CFHR1 gene [loss2(EXON:2-6)] were found in two patients. All patients received early treatment with plasma exchange and corticosteroid therapy. Six patients were given immunosuppressive agents (cyclophosphamide and/or mycophenolate mofetil) for persistent proteinuria. The follow-up period was 12–114 months. Four of 8 patients achieved complete remission, 3 achieved partial remission, and 1 died. Relapse occurred in two patients.Conclusion Children with anti-CFH Ab-associated HUS were mainly school-aged and predominantly male, with onset times of summer and winter. Digestive and upper respiratory tract infections were common prodromal infections. Plasma exchange combined with methylprednisolone pulse therapy in the acute phase and cyclophosphamide or mycophenolate mofetil treatment for maintenance can be utilized in children with anti-CFH Ab-associated HUS if eculizumab is not available.

The microbial contamination of food poses a threat to human health. Chestnut shells, which are byproducts of chestnut processing, contain polyphenols that exert various physiological effects, and thus have the potential to be used in food preservation. This study investigates the bacteriostatic effect and mechanism(s) of the action of chestnut shell polyphenols (CSPs) on three food-spoilage bacteria, namely Bacillus subtilis, Pseudomonas fragi, and Escherichia coli. To this end, the effect of CSPs on the ultrastructure of each bacterium was determined using scanning electron microscopy and transmission electron microscopy. Moreover, gene expression was analyzed using RT-qPCR. Subsequent molecular docking analysis was employed to elucidate the mechanism of action employed by CSPs via the inhibition of key enzymes. Ultrastructure analysis showed that CSPs damaged the bacterial cell wall and increased permeability. At 0.313 mg/mL, CSPs significantly increased the activity of alkaline phosphatase and lactate dehydrogenase, as well as protein leakage (p < 0.05), whereas the activity of the tricarboxylic acid (TCA) cycle enzymes, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, were inhibited (p < 0.05). The expression levels of the TCA-related genes gltA, icd, sucA, atpA, citA, odhA, IS178_RS16090, and IS178_RS16290 are also significantly downregulated by CSP treatment (p < 0.05). Moreover, CSPs inhibit respiration and energy metabolism, including ATPase activity and adenosine triphosphate (ATP) synthesis (p < 0.05). Molecular docking determined that proanthocyanidins B1 and C1, the main components of CSPs, are responsible for the antibacterial activity. Therefore, as natural antibacterial substances, CSPs have considerable potential for development and application as natural food preservatives.

Fatigue is a phenomenon caused by the disorder of energy coordination in the body, and prolonged exercise fatigue will lead to related diseases. Polyphenols have obvious biological activities, such as anti-oxidation, anti-tumor and so on. At present, polyphenols have been proved to have anti-fatigue effect, which can relieve exercise fatigue by regulating the AMPK signaling pathway to regulate oxidative stress, energy metabolism and inflammation, as well as substrate metabolism. In this paper, the generation and mechanism of exercise fatigue, the source of anti-fatigue polyphenols and the action mechanism of anti-fatigue polyphenols are systematically reviewed in order to provide reference for the research and development of anti-fatigue functional foods with polyphenols.

ObjectiveTo summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children.MethodsThe clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed.ResultsAmong the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age. There were 7 symptomatic patients, including 6 boys and 1 girl. All 7 patients presented with acral neuralgia. Five patients had little or no sweating. Five patients presented with cutaneous angiokeratoma. Two patients had abdominal pain. One patient developed joint symptoms. Four patients had corneal opacity. One patient had hearing loss; one patient had short stature. One patient had mild proteinuria and 1 patient had dysplasia of the right kidney with decreased eGFR (55.28 ml/min.1.73 m2). The left ventricular mass index was slightly elevated in 1 patient. Three patients had mild obstructive ventilatory dysfunction; a small amount of effusion in the intestinal space of the lower abdomen or mild fatty liver was found in 2 patients. Partial empty sella turcica in 1 patient. A total of 6 GLA gene variants were detected in 10 children, among which C.1059_1061delGAT (p.met353del) was a newly discovered mutation. Five children received ERT, of which 4 were treated with agalsidase beta and 1 was treated with agalsidase alpha. Only 1 patient had anaphylaxis. Lyso-GL-3 levels decreased significantly in the first 3 months of ERT initiation and remained relatively stable thereafter in 3 patients. The Lyso-GL-3 level was decreased, but renal impairment continued to progress in 1 patient treated with agalsidase alpha.ConclusionThe clinical manifestations of FD in childhood are diverse, and it is necessary to make a definite diagnosis by combining family history, enzyme activity, biomarkers, gene testing and other indicators. Pedigree screening and high-risk population screening are helpful for early identification, early diagnosis and early treatment. No serious adverse reactions were found during the short-term treatment with agalsidase alpha and beta.

IntroductionThyroid hormone receptor β (THR-β) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-β agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. MethodsWe conducted luciferase reporter gene assays to assess the activation of THR-β and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. ResultsCompared with MGL-3196, CS271011 showed higher THR-β activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. ConclusionsCS271011 is a potent and liver-targeted THR-β agonist for treating lipid metabolism disorders.

This study prepared hawthorn polyphenol microcapsules (HPM) by microencapsulation and revealed that its potential mechanism of action in fatigued mice involves regulation of AMPK signaling pathway and balancing the intestinal microflora. Spray drying process improved thermal stability of hawthorn polyphenol. After HPM treatment, the weight-bearing swimming ability of fatigued mice was significantly improved (p

Castanea mollissima shells are a by-product of Chinese chestnut processing and contain many polyphenols. Macrophage polarization plays an important role in the progression of atherosclerosis (AS). We investigated the action of Castanea mollissima shell polyphenols (CSPs), with proanthocyanidin C1 and proanthocyanidin B1 as the main phenolic components, on macrophages. CSPs (40 μg/mL) significantly decreased inflammatory cytokines secretion in M1-type macrophages (p

Exercise fatigue can exert deleterious effects on the body. This study evaluated the effects and mechanisms by which Lonicera caerulea berry polyphenols extract (LCBP) improved the treadmill endurance of mice. Comparison was performed between the effects at 25°C and low temperatures (-5°C). Energy storage, product metabolism, and other biochemical indices were determined using vitamin C (VC) as a positive control. Co-immunoprecipitation was performed to detect the interaction between different proteins. Dietary supplementation with LCBP significantly prolonged the exhaustion time during treadmill exercise by 20.4% (25 °C) and 27.4% (-5 °C). LCBP significantly regulated the expression of antioxidant and inflammatory proteins, Bcl-2 /Bax apoptosis proteins, and the PKCα -NOx2 / Nox4 pathway proteins, and activated the expression of AMPK-PGC1α -NRF1-TFAM proteins in skeletal muscle mitochondria. The gene and protein expression of miRNA-133a/IGF-1/PI3K/Akt/mTOR in skeletal muscle cells was also activated. Molecular docking confirmed that the main components of LCBP such as cyanidin-3-glucoside, catechin, and chlorogenic acid, have strong binding affinity toward AMPKα. LCBP alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, and apoptosis of skeletal muscle cells, enhances mitochondrial biosynthesis and cell proliferation, reduces fatigue, and enhances performance. These effects are also significant in a low-temperature environment (Graphical Abstract). Consequently, these results provide novel insights into the anti- fatigue roles of LCBP in exercise fatigue.

Background: Peripheral T-cell lymphoma (PTCL) is an extensive class of biologically and clinically heterogeneous diseases with dismal outcomes. The histone deacetylase inhibitor (HDACi) romidepsin was approved for relapsed and refractory (R/R-PTCL) in 2011. This meta-analysis was performed to assess the efficacy and safety of romidepsin in PTCL.Methods: We searched for articles on the HDAC inhibitor romidepsin in the treatment of PTCL in Embase, Web of Science, and PubMed. The methodology is further detailed in PROSPERO (CRD42020213651, CRD42020213553). The 2-year overall survival (OS), 2-year progression-free survival (PFS), and their corresponding to 95% confidence intervals (CIs) were measured. Besides, corresponding 95% CIs were pooled for the complete response (CR), partial response (PR), duration of response (DoR), and risk of adverse events (AEs).Results: Eleven studies containing 388 patients were incorporated into the quantitative synthesis, of which R/R-PTCL patients were the dominant portion, accounting for 94.3% (366/388). For all studies, the CR rate was 20% (95% CI, 13–27%, random effects model), and the PR rate was 18% (95% CI, 12–25%, random effects model). The 2-year OS was 48% (95% CI, 38–59%, fixed effects model), and the 2-year PFS was 17% (95% CI, 13–21%, fixed effects model). There were no significant differences between romidepsin monotherapy and romidepsin plus additional drugs. Hematological toxicities, such as lymphopenia and granulocytopenia, remained the most continually happening grade 3 or higher AEs, accounting for 46 and 28%, respectively. None of the studies reported any drug-related mortality.Conclusions: Considering that most of the included patients had R/R-PTCL, the addition of romidepsin significantly enhance the efficacy. And AEs were tolerable as the grade 3/4 AEs in romidepsin monotherapy was 7% (95% CI, 6–8%). It is imperative to further expand the first-line application of romidepsin and carry out personalized therapy based on epigenomics, which will improve the survival of PTCL patients.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213651 and https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213553.

Tumor suppressor protein P53 induces cycle arrest and apoptosis by mediating the transcriptional expression of its target genes. Mutations causing conformational abnormalities and post-translational modifications that promote degradation are the main reasons for the loss of P53 function in tumor cells. Reporter gene assays that can scientifically reflect the biological function can help discover the mechanism and therapeutic strategies that restore P53 function. In the reporter gene system of this work, tetracycline-inducible expression of wild-type P53 was used to provide a fully activated state as a 100% activity reference for the objective measurement of biological function. It was confirmed by RT-qPCR, cell viability assay, immunofluorescence, and Western blot analysis that the above-mentioned reporter gene system could correctly reflect the differences in biological activity between the wild-type and mutants. After that, the system was tentatively used for related mechanism research and compound activity evaluation. Through the tetracycline-induced co-expression of wild-type P53 and mutant P53 in exact proportion, it was observed that the response modes of typical transcriptional response elements (TREs) to dominant negative P53 mutation effect were not exactly the same. Compared to the relative multiple-to-solvent control, the activity percentage relative to the 100% activity reference of wild-type P53 can better reflect the actual influence of the so-called P53 mutant reactivator. Similarly, relative to the 100% activity reference, it can objectively reflect the biological effects caused by the inhibitor of P53 negative factors, such as MDM2. In conclusion, this study provides a 100% activity reference and a reliable calculation model for relevant basic research and drug development.

Abstract Background Extracting relations between bio-entities from biomedical literature is often a challenging task and also an essential step towards biomedical knowledge expansion. The BioCreative community has organized a shared task to evaluate the robustness of the causal relationship extraction algorithms in Biological Expression Language (BEL) from biomedical literature. Method We first map the sentence-level BEL statements in the BC-V training corpus to the corresponding text segments, thus generating hierarchically tagged training instances. A hierarchical sequence labeling model was afterwards induced from these training instances and applied to the test sentences in order to construct the BEL statements. Results The experimental results on extracting BEL statements from BioCreative V Track 4 test corpus show that our method achieves promising performance with an overall F-measure of 31.6%. Furthermore, it has the potential to be enhanced by adopting more advanced machine learning approaches. Conclusion We propose a framework for hierarchical relation extraction using hierarchical sequence labeling on the instance-level training corpus derived from the original sentence-level corpus via word alignment. Its main advantage is that we can make full use of the original training corpus to induce the sequence labelers and then apply them to the test corpus.

Negative life events, such as the death of a loved one, are an unavoidable part of life. These events can be overwhelmingly stressful and may lead to the development of mental health disorders. To mitigate these adverse developments, prior literature has utilized measures of psychological responses to negative life events to better understand their effects on mental health. However, psychological changes represent only one aspect of an individual's potential response. We posit measuring additional dimensions of health, such as physical health, may also be beneficial, as physical health itself may be affected by negative life events and measuring its response could provide context to changes in mental health. Therefore, the primary aim of this work was to quantify how an individual's physical health changes in response to negative life events by testing for deviations in their physiological and behavioral state (PB-state). After capturing post-event, PB-state responses, our second aim sought to contextualize changes within known factors of psychological response to negative life events, namely coping strategies. To do so, we utilized a cohort of professionals across the United States monitored for 1 year and who experienced a negative life event while under observation. Garmin Vivosmart-3 devices provided a multidimensional representation of one's PB-state by collecting measures of resting heart rate, physical activity, and sleep. To test for deviations in PB-state following negative life events, One-Class Support Vector Machines were trained on a window of time prior to the event, which established a PB-state baseline. The model then evaluated participant's PB-state on the day of the life event and each day that followed, assigning each day a level of deviance relative to the participant's baseline. Resulting response curves were then examined in association with the use of various coping strategies using Bayesian gamma-hurdle regression models. The results from our objectives suggest that physical determinants of health also deviate in response to negative life events and that these deviations can be mitigated through different coping strategies. Taken together, these observations stress the need to examine physical determinants of health alongside psychological determinants when investigating the effects of negative life events.

A combination of vermicast and sawdust mixed medium is commonly used in horticulture, but the added benefit of microbial inoculation and mechanism of nutrient availability are unknown. This study was done to determine nutrient mineralization and nutrient release patterns of different combinations or a mix of vermicast-sawdust growing media amended with or without Trichoderma viride (105 spores/g). The mixed-media treatments were (1) 80% vermicast+20% sawdust; (2) 60% vermicast+40% sawdust; (3) 40% vermicast+60% sawdust; (4) 20% vermicast+80% sawdust; and (5) sawdust alone (control). Total dissolved solids, electric conductivity and salinity increased with each sampling time following submergence in deionized. Nutrients released from media without T. viride were significantly higher than the corresponding media with added T. viride. Overall, the starting total nitrogen of the different media did not change during the incubation period, but nitrate-nitrogen was reduced to a negligible amount by the end of day 30 of incubation. A repeated measures analysis showed a significant effect of Time*T. viride*Treatment on total dissolved solids. Redundancy analysis demonstrated a positive and strong association between media composed of ≥40% vermicast and ≤60% sawdust with or without T. viride and mineral nutrients released, electrical conductivity, total dissolved solids and salinity. These findings suggest that fast-growing plants may benefit from 40% to 60% vermicast added to 40% to 60% sawdust without T. viride while slow-growing plants can benefit from the same mixed medium combined with the addition of T. viride. Further investigation is underway to assess microbial dynamics in the mixed media and their influence on plant growth.

A study was performed to assess nutrient release from biochar inoculated with solid vermicast (SVB), vermicast tea (VTB), deionized water (DWB), uninoculated biochar (Bioc), and Promix-BX (Pro-BX). The growth response of Swiss chard (Beta vulgaris subsp. vulgaris) cv. Rhubarb chard was also assessed. Comparatively, nutrients were released slowly from treatments SVB and VTB compared to the other treatments. The rate of nutrient release determined by total dissolved solids and electric conductivity from the Pro-BX was the highest. The trend for the plant growth components, total leaf surface area and leaf fresh weight at first harvest, was Pro-BX > Bioc > DWB = SVB > VTB. The only treatment that increased total leaf area and leaf fresh weight at the second harvest by approximately 1.02- and 1.88-fold was VTB. Leaf fresh weight was significantly reduced by approximately 0.33-fold for DWB, 0.28-fold for Bioc, and 0.70-fold for Pro-BX but was not altered by SVB at the second harvest as compared to the first harvest. A 2-dimensional principal component analysis (PCA) biplot confirmed that treatment Pro-BX increased plant growth components at the first harvest only. The locations of SVB and VTB on the PCA biplot confirmed their efficacies, which led to increases in the plant growth components at the second harvest. Overall, the VTB adsorbed more nutrients onto its surface that were slowly released to enhance the Swiss chard cv. Rhubarb chard plant growth at the second harvest. Further studies should consider microbial activities.

Chestnut is popular worldwide for its unique flavor, high eating quality and nutrition. Here, we evaluated the influence of phosphorylation and acetylation on the structural, physicochemical and functional properties of chestnut starch. Scanning electron micrographs showed the agglomeration of starch granules and the appearance of numerous dents on the starch granule surface under phosphorylation and acetylation. X-ray diffractograms confirmed that the modification treatments did not affect the C-type crystal pattern, but reduced the relative crystallinity of the chestnut starch, particularly phosphorylation. Moreover, modification improved the paste transparency of the starch. Differential scanning calorimeter analysis revealed that the gelatinization temperature and enthalpy of the starch decreased with the increasing substitution degree, particularly in phosphorylated starch. The Rapid Visco Analyser analysis demonstrated that phosphorylation could greatly improve the pasting properties of chestnut starch. In addition, phosphorylated and acetylated starch had a smaller amount of slowly digested starch and a larger amount of resistant starch relative to native chestnut starch. In conclusion, the functional and physicochemical properties of chestnut starch can be significantly improved through phosphorylation and acetylation, demonstrating its great application potential as a food additive.

A wild Lonicera caerulea berry extract rich in polyphenols (LCBP) is widely used as a food supplement and additive. The main active components are cyanidin-3-glucoside, (+)-catechin, and chlorogenic acid. The aim of this study was to examine the hypocholesterolemic effects of LCBP in high cholesterol diet (HCD)-induced hypercholesterolemia in Sprague Dawley rats and the associated changes in cholesterol metabolism. Rats were fed an HCD with or without LCBP (75, 150, and 300 mg/kg body weight) for 12 weeks. LCBP at 150 and 300 mg/kg was effective for reducing cholesterol accumulation (p

Social networks influence health-related behavior, such as obesity and smoking. While researchers have studied social networks as a driver for diffusion of influences and behavior, it is less understood how the structure or topology of the network, in itself, impacts an individual's health behavior and wellness state. In this paper, we investigate whether the structure or topology of a social network offers additional insight and predictability on an individual's health and wellness. We develop a method called the Network-Driven health predictor (NetCARE) that leverages features representative of social network structure. Using a large longitudinal data set of students enrolled in the NetHealth study at the University of Notre Dame, we show that the NetCARE method improves the overall prediction performance over the baseline models-that use demographics and physical attributes-by 38%, 65%, 55%, and 54% for the wellness states-stress, happiness, positive attitude, and self-assessed health-considered in this paper.

Seven varieties of Chinese dwarf cherries were evaluated and compared with respect to their weight, diameter, titratable acidity, total soluble solids, color, polyphenol contents, ascorbic acid levels, anthocyanin profiles, enzymatic activity, and antioxidant capacity. The fruits are rich in phenolic content (339.07–770.30 mg/100 g fresh weight). Nine anthocyanins were obtained from fruits after chromatographic separation and their structures analyzed using HPLC-ESI-MS/MS. Cyanidin-3-glucoside was the major anthocyanin with 50.36–78.39% concentration. Three anthocyanins were reported for the first time in these cherries. They exhibit low polyphenol oxidase and peroxidase activities, but their superoxide dismutase activity is high (572.75–800.17 U/g FW). The highest amounts of soluble solid content (15.67 Brix %), total titratable acid (1.90%), ascorbic acid (18.47 mg/100 g FW), and total anthocyanin (152.66 mg/100 g FW) were observed. Three methods (DPPH-scavenging ability, oxygen radical absorbance capacity assay, and cellular antioxidant activity assay) were employed to evaluate the antioxidant capacity of the phenolic extracts of these cherries. Number 5 has the highest values of ORAC and CAA of 205.68 μmol TE/g DM and 99.67 μmol QE/100 g FW, respectively.

In this study, we analyzed the complete mitochondrial genome of the spike-topped apple snail, Pomacea diffusa Blume, 1957 (Gastropoda: Ampullariidae). The mitochondrial genome of P. diffusa was 16,373 bp, consisting 13 protein-coding genes, 2 rRNAs, and 22 tRNAs and a non-coding region with a 12 bp repeat unit. There were 29 mitochondrial genes of P. diffusa are distributed on the H-strand, and the other eight tRNA genes encoded on the L-strand. The average AT content of 13 protein-coding genes was 68.7%. A phylogenetic analysis showed that there was a close relationship between P. diffusa and invasive apple snail species, Pomacea canaliculata and Pomacea aff. maculata.