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Traditionally, Fischer–Tropsch (FT) synthesis is performed using thermal catalysts and syngas (CO and H2) under high‐pressure and high‐temperature conditions. However, this study introduces an approach that relies on FT chemistry assisted by electrochemistry, referred to here as direct electrochemical (EC) FT chemistry, under ambient conditions. A series of CH4, CnH2n, and CnH2n+2 hydrocarbons (n = 1–7) is successfully produced over gold (Au) nanoparticle‐loaded perovskite strontium titanate (SrTiO3) nanostructures grown on rutile TiO2 supported on Ti. Au (1.0 nm)–SrTiO3 shows the best interface formation, with the highest Faradaic efficiency for C2+ hydrocarbons. This direct EC‐FT process proceeds via a C─C coupling chain growth reaction at the Au‐SrTiO3 interface as evidenced by the hydrocarbon weight distribution analysis and density functional theory calculations. The robust combination of experimental and computational findings reveals that optimum conditions for producing surface hydrogenation and C─C coupling polymerization, initiated by surface *CO and *H are achieved by controlling the undercoordinated Au at the perimeter sites of supported Au nanoparticles and by ensuring a harmonized density of states between Au and SrTiO3. This EC‐FT process opens a promising avenue for the direct conversion of CO2 and H2O into value‐added long‐chain hydrocarbons. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: The objective of the study was to analyse the prevalence, incidence, and death of alcohol‐associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time. Methods: The study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15–29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time. Results: In 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age‐adjusted prevalence rate per 100,000 increased in the 25–29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20–24 (p = 0.302) and ages 15–19 (p = 0.160). Prevalence increased significantly from age 15–19 to 20–24 (19‐fold increase) and from age 20–24 to 25–29 (2.5‐fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three‐quarters of countries and territories experienced an increase in ALD incidence rates in young adults. Conclusion: Over two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters. Methods: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL. Results: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non‐highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD. Conclusion: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure–function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the implications of drug intoxication (DI) on donor utilization and outcomes in liver transplantation (LT). Methods: The UNOS STAR database was evaluated for all potential donors and adult, first‐time, whole LT between 2005 and 2019. Logistic regression analyses evaluated liver utilization; proportional hazards modeling assessed risk of 1‐year graft loss. Results: A total of 132 783 potential donors (10 205, 7.7% from DI), and 90 612 adult LT were identified (7490, 8.3% from DI). DI donors had median age 32 years (IQR 26–40 years, p <.001), were 42.6% female (n = 4346), and 15.5% were DCD donors (n = 1583). Utilization of DI donors changed over time, such that by 2015–2019 they were the most likely donor cause of death (COD) to be utilized. Among LT recipients, there were insignificant differences (<2% variance) in age, gender, ethnicity, and etiology of liver disease according to donor COD. Recipients with MELD scores >30 more frequently received grafts from donors with trauma (23.8%) and DI (21.8%) versus cardiovascular (20.0%) and CVA/stroke (19.9%, p <.001). Among DBD donors, DI‐COD was associated with superior 1‐year graft survival compared to donors from trauma (HR 1.172, 95% CI 1.057–1.300) and CVA/stroke (HR 1.404, 95% CI 1.264–1.561, p <.001). Donor COD was not significantly associated with 1‐year graft loss among DCD donors. Conclusions: There is an increased likelihood of donor utilization when COD is drug overdose and an increased likelihood of 1‐year graft survival compared to donors from trauma, CVA/stroke, and other COD. [ABSTRACT FROM AUTHOR]

Anthracyclines remain the cornerstone of numerous chemotherapeutic protocols, with beneficial effects against haematological malignancies and solid tumours. Unfortunately, the clinical usefulness of anthracyclines is compromised by the development of cardiotoxic side effects, leading to dose limitations or treatment discontinuation. There is no absolute linear correlation between the incidence of cardiotoxicity and the threshold dose, suggesting that genetic factors may modify the association between anthracyclines and cardiotoxicity risk. And the majority of single nucleotide polymorphisms (SNPs) associated with anthracycline pharmacogenomics were identified in the ATP‐binding cassette (ABC) and solute carrier (SLC) transporters, generating increasing interest in the pharmacogenetic implications of their genetic variations for anthracycline‐induced cardiotoxicity (AIC). This review focuses on the influence of SLC and ABC polymorphisms on AIC and highlights the prospects and clinical significance of pharmacogenetics for individualised preventive approaches. [ABSTRACT FROM AUTHOR]

Functional constipation (FC) has a negative impact on patients' quality of life. We hypothesized that dietary supplementation with xylo‐oligosaccharides (XOS) or fructo‐oligosaccharides (FOS) would improve constipation symptoms by influencing the gut microbiota. A randomized double‐blind controlled trial was conducted in FC patients. Patients were randomly divided into 6 groups and given a dietary supplement containing XOS at doses of 3, 5, or 10 g/day, FOS at doses of 10 and 20 g/day, or placebo at 5 g/day for one month. We compared improvements in gastrointestinal function after the intervention using the Bristol Stool Form Scale (BSFS), Cleveland Clinic Constipation Score (CCCS), and Quality of Life Scale for Patients with Constipation (PAC‐QoL). 16S rRNA sequencing was used to assess changes in the structure of the gut microbiota. Changes in individual bacteria had significant effects in reducing gastrointestinal symptoms during the intervention, even though the flora structure remained unchanged from baseline. Compared to FOS, XOS enriched Bifidobacterium at a lower dose, and patients receiving XOS supplementation showed significant improvements in constipation symptoms without side effects such as diarrhea and flatulence. [ABSTRACT FROM AUTHOR]

Tripyrromethane‐based tripodal compounds 1–3 were synthesized as anion receptors. It was revealed by 1H NMR spectroscopic analyses carried out in CDCl3 that tripyrromethane 1 with an ester group was capable of recognizing F−, Cl−, Br−, and H2PO4− with relatively high selectivity for F−. By contrast, receptor 2 having an additional hydrogen bond donor of an amide group binds F− and H2PO4− with much improved affinity relative to receptor 1. On the other hand, receptor 3 bearing formyl groups on its two pyrrole subunits showed markedly enhanced selectivity for F− presumably due to the increased acidity of the pyrrolic NHs and the resulting strengthened intermolecular hydrogen bonds. In addition, tripodal receptors 1–3 were found to bind H2PO4−, a tetrahedral oxyanion, more efficiently than 2‐dimensional macrocyclic calix[4]pyrrole 4. [ABSTRACT FROM AUTHOR]

Gleditsia sinensis is a species endemic to China, an ecologically economic multipurpose tree with great development potential, which could be used as medicine, food, industrial materials and wood. It is well known that the standardized description of plant development stages according to their phenological characteristics not only is crucial for conduct of various agronomic practices, but also facilitates the exchange of new findings based on the same understanding of the plant. However, a uniform phenology scale of G. sinensis has rarely been reported, despite its expanding plant area and rapid development of this industry over the past few years. Thus, phenological events of G. sinensis were monitored based on the BBCH scale during two consecutive years in this study. Eight of the 10 BBCH stages described in detail by combining numbers and letters based on its species characteristic were accurately recorded, including bud development (0), leaf development (1), shoot development (3), inflorescence emergence (5), flowering (6), pod development (7), maturity of pod (8) and senescence (9). As far as we know, it is the first time that a special phenological rhythm for G. sinensis has been developed using an extended BBCH scale, which not only provides the basis for other basic research, but also assists growers in conducting planting management practices. [ABSTRACT FROM AUTHOR]

Objectives: The signet‐ring cell carcinoma (SRCC) of the stomach is highly invasive. Patients with stage III gastric SRCC usually experience tumor recurrence within 2 years after radical surgery. Unfortunately, there is no effective treatment to postpone recurrence following adjuvant chemotherapy. Our study aimed to explore the safety and efficacy of neoantigen‐reactive T lymphocytes (NRTs) in patients with stage III gastric SRCC. Methods: The study included 20 patients with stage III gastric SRCC who received radical surgery and adjuvant chemotherapy. Following the adjuvant chemotherapy, they underwent treatment with a range of one to four cycles of personalised neoantigen‐reactive T cells. The primary endpoint was the median progression‐free survival (mDFS). The secondary endpoint was safety and immune responses. The median duration of follow‐up was 41 months (95% CI: 39–42.9 months). Results: Our results showed that patients who received adjuvant neoantigen‐reactive T‐cell immunotherapy demonstrated a propensity towards prolonged disease‐free survival (DFS) and overall survival (OS) in comparison to previous studies. The 2‐year DFS and OS rates reached 73.7% and 95%, respectively, whereas the 5‐year DFS and OS rates were 44% and 69%. The median DFS was 41 months (95% CI: 28.9–53.1 months) and the median OS was not reached. In addition, there was a significant increase in serum concentrations of IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α and IFN‐γ after cell immunotherapy. The adverse reactions were mild. Conclusion: In conclusion, adjuvant immunotherapy with NRTs showed promising efficacy alongside a manageable safety profile. [ABSTRACT FROM AUTHOR]

While there is growing evidence that many epigenetically silenced genes in cancer are tumour suppressor candidates, their significance in cancer biology remains unclear. Here, we identify human Neuralized (NEURL), which acts as a novel tumour suppressor targeting oncogenic Wnt/β‐catenin signalling in human cancers. The expression of NEURL is epigenetically regulated and markedly suppressed in human colorectal cancer. We, therefore, considered NEURL to be a bona fide tumour suppressor in colorectal cancer and demonstrate that this tumour suppressive function depends on NEURL‐mediated oncogenic β‐catenin degradation. We find that NEURL acts as an E3 ubiquitin ligase, interacting directly with oncogenic β‐catenin, and reducing its cytoplasmic levels in a GSK3β‐ and β‐TrCP‐independent manner, indicating that NEURL‐β‐catenin interactions can lead to a disruption of the canonical Wnt/β‐catenin pathway. This study suggests that NEURL is a therapeutic target against human cancers and that it acts by regulating oncogenic Wnt/β‐catenin signalling. Synopsis: Neuralized (NEURL) is a novel tumour suppressor targeting the oncogenic Wnt/β‐catenin pathway in colorectal cancer by promoting β‐catenin degradation independent of GSK3β and β‐TrCP. NEURL hypermethylation is associated with poor outcomes in patients with colon cancer.NEURL acts as a tumour suppressor in colon cancer by inhibiting cell proliferation and interrupting tumorigenesis.NEURL targets β‐catenin as an E3 ubiquitin ligase impairing oncogenic WNT signalling in colorectal cancer. [ABSTRACT FROM AUTHOR]

The arrangement of atoms comprising a material determines its properties. Thus, atom arrangement controllability can substantially facilitate the creation of new materials such as functional materials. Relevant materials science research has relied heavily on heat treatments. This study investigates the phenomenon of atom rearrangement by applying a high-frequency alternating current without heating. The proposed method spontaneously rearranges atoms to produce a dense crystal plane oriented parallel to the electron flow. The atoms are "shaken" by generating mechanical interaction between electrons and atoms. Transmission electron microscopy reveals the enlarged crystal grains and an increase in close-packed planes resulting from the self-alignment of the atoms along the direction of electron flow. Conventional heat treatments cannot result in such phenomena because heat treatments induce random vibration of the atoms. In contrast, the current flow in the high-frequency alternating current enables direction-specific vibration of the atoms. This novel technique could be applied to develop new functional materials that are difficult to obtain via conventional heat treatment methods. Furthermore, this atom rearrangement technology can be applied to expand the field of materials science research. [ABSTRACT FROM AUTHOR]

This mini‐review summarizes catalytic asymmetric synthetic methodologies for preparing 2,5‐diketopiperazine (DKP) frameworks since 1990, with two types of synthetic precursor, namely linear materials and cyclic pre‐chiral substrates, discussed. This review provides guidance for the further design and development of novel catalytic asymmetric methods for preparing functionalized DKP‐containing molecules. [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials indicated the addition of anti‐PD‐1 antibody remarkably improved the efficacy of trastuzumab and chemotherapy in patients with HER2‐positive gastric/gastroesophageal junction (GEJ) cancer. However, no real‐world experiences have been reported yet. Methods: We retrospectively analyzed 1212 patients with gastric/GEJ cancer treated at Nanjing Drum Tower Hospital between 2019 and 2022. Among 138 patients with HER2‐positive gastric/GEJ cancer, 47 patients receiving at least two doses of the combination regimen with anti‐PD‐1 antibody, trastuzumab, and chemotherapy were recruited in the study population, and 38 out of 47 patients with measurable disease were included in the efficacy population. Progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were reported. Results: In the study population, 37 (78.7%) received the study therapy as a first‐line treatment. In the efficacy population, the ORR and DCR were 76.3% and 94.7%, respectively. The overall median PFS was 9.1 months (95% confidence interval [CI] 6.3–11.9 months). For the first‐line treatment, the mPFS was 10 months, and 7 months for the second‐line. Among 14 patients who failed the study treatment, three (21.4%) developed brain metastasis as the first failure site. No significant association was found between PFS and the expression of PD‐L1. 22.2% of patients developed grade 3 treatment‐related adverse events (TRAEs). No treatment‐related grade ≥4 adverse events or deaths occurred. Conclusion: This real‐world study validated the combination regimen's high efficacy and good tolerance in patients with HER2‐positive gastric/GEJ cancer. An increased incidence of brain metastasis was observed in patients who failed this regimen. [ABSTRACT FROM AUTHOR]

Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumor immune response. Here, a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy is generated. PNVAC triggers superior protective efficacy against tumor recurrence and promotes longer survival than free neoantigens, especially when combined with anti‐PD‐1 treatment in a murine tumor model. A phase I clinical trial (ChiCTR1800017319) is initiated to evaluate the safety, immunogenicity, and prophylactic effect of PNVAC on preventing tumor recurrence in patients with high‐risk gastric/gastroesophageal junction cancer after adjuvant chemotherapy of postsurgical resection. The one‐ and two‐year disease‐free survival rates are significantly higher than historical record. PNVAC induces both CD4+ and CD8+ T cell responses as well as antigen‐experienced memory T cell phenotype. Furthermore, the immune response is persistent and remains evident one year after the vaccination. This work provides a safe and feasible strategy for developing neoantigen vaccines to delay gastric cancer recurrence after surgery. [ABSTRACT FROM AUTHOR]

In order to pursue faster growth and development of weaned piglets, increased dietary protein (CP) levels were favoured by the pig industry and the feed industry. The digestive organs of piglets were not fully developed at weaning, and the digestive absorption capacity of protein was limited. High‐protein diets can cause allergic reactions in piglets, destroy intestinal structural integrity, reduce immunity, and cause intestinal flora imbalance. Undigested proteins were prone to produce toxic substances, such as ammonia and biogenic amines, after fermentation in the hindgut, which negatively affects the health of the intestine and eventually causes reduced growth performance and diarrhoea in piglets. This review revealed the mechanism of diarrhoea caused by high‐protein diets in weaned piglets and provided ideas for preventing diarrhoea in weaned piglets. [ABSTRACT FROM AUTHOR]

Background: Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown.Methods: The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively.Results: The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS.Conclusions: More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA. [ABSTRACT FROM AUTHOR]

Background: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC.Methods: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts.Results: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12).Conclusions: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment. [ABSTRACT FROM AUTHOR]

In an article published in Advanced Energy Materials, researchers Chang Woo Myung, Youngku Sohn, and their team explore the direct electrochemical Fischer-Tropsch chemistry of C1-C7 hydrocarbons using Au-SrTiO3 catalysts. They demonstrate the production of long-chain hydrocarbon fuels through electrochemistry, utilizing CO2 and H2O. The researchers predict the underlying mechanism at the interface using density functional theory calculations. This innovative conversion process offers potential for sustainable fuel production under ambient conditions. [Extracted from the article]

Tripodal ion pair receptors 1 and 2 consisting of tris(pyridine‐2‐ylmethyl)amine as a cation binding site linked with nitrophenyl urea or amidonitroindole groups as anion binding motifs have been synthesized. 1H NMR spectroscopic analyses carried out in 10 % DMSO in acetonitrile revealed that both ion pair receptors 1 and 2 are able to bind the LiCl ion pair with high selectivity over NaCl, KCl, RbCl, and CsCl. 1H NMR spectroscopic analyses in combination with molecular mechanics calculations proved that the lithium cation is bound to the tris(pyridin‐2‐ylmethyl)amine subunit while the chloride anion interacts with the NHs of urea or amido indole groups via hydrogen bonds. The addition of fluoride to the lithium cation complexes of receptors 1 and 2 leads to the release of the lithium cation from the receptors whereas chloride and bromide are co‐bound with lithium forming LiCl and LiBr ion pair complexes, respectively. The affinity of receptor 1 for the lithium cation was found to be improved by 5.0‐fold when the counter anion of Cl− is co‐bound within the receptor. [ABSTRACT FROM AUTHOR]

Serum alpha‐fetoprotein and radiologic imaging are the most commonly used tests for early diagnosis and dynamic monitoring of treatment response in hepatocellular carcinoma (HCC). However, the accuracy of these tests is limited, and they may not reflect the underlying biology of the tumor. Thus, developing highly accurate novel HCC biomarkers reflecting tumor biology is a clinically unmet need. Circulating tumor cells (CTCs) have long been proposed as a noninvasive biomarker in clinical oncology. Most CTC assays utilize immunoaffinity‐based, size‐based, and/or enrichment‐free mechanisms followed by immunocytochemical staining to characterize CTCs. The prognostic value of HCC CTC enumeration has been extensively validated. Subsets of CTCs expressing mesenchymal markers are also reported to have clinical significance. In addition, researchers have been devoting their efforts to molecular characterizations of CTCs (e.g. genetics and transcriptomics) as molecular profiling can offer a more accurate readout and provide biological insights. As new molecular profiling techniques, such as digital polymerase chain reaction, are developed to detect minimal amounts of DNA/RNA, several research groups have established HCC CTC digital scoring systems to quantify clinically relevant gene panels. Given the versatility of CTCs to provide intact molecular and functional data that reflects the underlying tumor, CTCs have great potential as a noninvasive biomarker in HCC. Large‐scale, prospective studies for HCC CTCs with a standardized protocol are necessary for successful clinical translation. [ABSTRACT FROM AUTHOR]

Background and objectives: The immunogenicity of vaccines is known to be attenuated in patients with end‐stage kidney disease due to uremia. Patients on dialysis were excluded from coronavirus disease 2019 (COVID‐19) vaccine trials; thus, the effectiveness of vaccines for this population is unclear. The aim of this study was to explore whether Asian dialysis patients can effectively produce an immune response after being vaccinated with the first dose of the ChAdOx1 nCoV‐19 vaccine. Design setting, participants, and measurements: In this prospective cohort study, we included Asian hemodialysis patients who received the ChAdOx1 nCoV‐19 vaccine. At 3 weeks after the first dose of vaccination, we assessed the humoral immune response by measuring anti‐SARS‐CoV‐2 S antibody titers. The primary outcome was the seropositive rate following vaccination, defined as an antibody titer greater than or equal to 0.8 U/ml. Factors associated with seropositivity were explored in multivariate logistic regression analyses. Results: In total, 434 participants were included. The mean age was 64 years, the mean dialysis vintage was 6 years, and 61% of the participants were men. At a mean time of 22 days from vaccination, 56% of the participants were seropositive. The vast majority (88%) had low antibody titers (< 15 U/ml). The multivariate logistic regression analyses showed that older age (every increase of 10 years, odds ratio [OR] 0.80, 95% CI 0.65–0.98, p = 0.03) was negatively associated with seropositivity and that higher Kt/V (every increase of 0.1, OR 1.14, 95% CI 1.01–1.28, p = 0.03) and higher serum albumin level (every increase of 0.1 g/dl, OR 1.09, 95% CI 1.02–1.18, p = 0.02) were positively associated with seropositivity. Conclusions: In Asian hemodialysis patients, the seropositive rate was low, and most had low antibody titers after the first dose of the ChAdOx1 nCoV‐19 vaccine. Younger age, better dialysis adequacy, and higher albumin levels were associated with seropositivity. [ABSTRACT FROM AUTHOR]

Summary: Organic‐inorganic lead halide perovskite solar cells (PSCs) have shown excellent characteristics for photovoltaic performance along with high power conversion efficiency (PCE) of 25.5%. Methylammonium lead iodide (CH3NH3PbI3) PSCs show effective photovoltaic performance but exhibit low utilization and instability in the ultraviolet (UV) region due to photodegradation. Therefore, there is a need for research aimed at increasing the stability of PSCs. Through their down‐conversion, PSCs can achieve high photovoltaic performance and stability by protecting against UV light and light‐harvesting in the visible region. In this study, europium (Eu; a lanthanide) was demonstrated to enhance the efficiency of PSCs and prevent degradation by UV light. The Eu‐complex poly(dimethylsiloxane) (PDMS) film enhanced the usability of the UV region by down‐converting UV light to visible light. In addition, Eu‐complex PDMS film has the advantages of being transparent and hydrophobic. Furthermore, it is easily detachable when the surface is contaminated. When Eu‐complex PDMS film was attached and compared with a reference device, it was confirmed that the PCE increased by up to 20% and that the short‐circuit current density also increased. Overall, Eu‐complex film was shown to increase the light‐harvesting of PSCs and enhance the stability in the UV region through the down‐conversion of UV light to visible light. [ABSTRACT FROM AUTHOR]

Resistance to irradiation (IR) remains a major therapeutic challenge in tumor radiotherapy. The development of novel tumor‐specific radiosensitizers is crucial for effective radiotherapy against solid tumors. Here, we revealed that remodeling tumor tissue penetration via tumor‐penetrating peptide internalizing arginine–glycine–aspartic acid RGD (iRGD) enhanced irradiation efficacy. The growth of 4T1 and CT26 multicellular tumor spheroids (MCTS) and tumors was delayed significantly by the treatment with IR and iRGD. Mechanistically, iRGD reduced hypoxia in MCTS and tumors, resulting in enhanced apoptosis after MCTS and tumors were treated with IR and iRGD. This is the first report that shows enhanced radiation efficacy by remodeling tumor‐specific tissue penetration with iRGD, implying the potential clinical application of peptides in future tumor therapy. [ABSTRACT FROM AUTHOR]

Activation of protein kinases after cocaine administration controls psychomotor behaviours by interacting with metabotropic receptors in the brain. This study identified how c-Jun N-terminal kinase (JNK) interacts with metabotropic glutamate receptor 5 (mGluR5) in vitro and in the caudate and putamen (CPu). The potential role of this interaction in the regulation of psychomotor behaviour was also evaluated after administration of cocaine. Active JNK phosphorylates a threonine residue at position 1055 in the carboxyl terminus (CT) of mGluR5 in vitro. The binding of active JNK to the D-motif within CT2 is necessary for that phosphorylation. Interaction of phosphorylated JNK and mGluR5 occurs in the CPu. Unilateral interference of the interaction decreases the repeated cocaine-induced increases in locomotor activity and conditioned place preference. These findings suggest that activation of JNK has the capability to interact with mGluR5 in the CPu. Phosphorylation of mGluR5 following the JNK-mGluR5 interaction may be responsible for the potentiation of behavioural sensitisation and cocaine-wanting behaviour in response to cocaine administration. [ABSTRACT FROM AUTHOR]

Novel asymmetric mono‐ and dialkylation reactions of α‐substituted 2,5‐diketopiperazines catalyzed by new chiral spirocyclic‐amide‐derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5‐diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis‐diastereo‐ and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5‐diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations. [ABSTRACT FROM AUTHOR]

Rats express a positive emotional state by emitting 50‐kHz ultrasonic vocalization (USV) calls in response to drug exposure. This study demonstrated the linking of glutamate receptors in the nucleus accumbens (NAc) to vocal expression of 50‐kHz USV calls after repeated cocaine administration in freely moving rats. Repeated systemic injections of cocaine (20 mg/kg/day, i.p.) for seven consecutive days increased the number of 50‐kHz USV calls. Intra‐NAc core infusion of the broad‐glutamate receptor antagonist, γDGG (50 nmol/side), decreased the repeated cocaine‐induced increase in the number of 50‐kHz USV calls. Intra‐NAc core infusion of the N‐methyl‐D‐aspartate (NMDA) receptor antagonist, MK801 (2 nmol/side), but not α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid or kainic acid receptor antagonist, CNQX disodium salt (2 nmol/side), decreased the number of 50‐kHz USV calls that had been elevated by repeated exposure to cocaine. Intra‐NAc core infusion of the group I metabotropic glutamate receptor subtype 5 (mGluR5), MPEP (0.5 nmol/side), MTEP (15 nmol/side) and inositol‐1,4,5‐trisphosphate receptor blocker, xestospongin C (0.004 nmol/side) decreased the cocaine‐induced increase in the number of USV calls. These data suggest that the NMDA receptor‐ and mGluR5‐dependent increase in intracellular Ca2+ concentrations in the NAc core is linked to a positive emotional state after repeated exposure to cocaine in rats. [ABSTRACT FROM AUTHOR]

The development of chemoresistance reduces the efficacy of anti‐cancer drugs. Cervical cancer is still one of the most common cancer types in developing countries. The oncogenic protein high mobility group AT‐hook 2 (HMGA2) is involved in the development and progression of tumors, although its role in chemoresistance of cervical cancer remains unclear. Here, we report that HMGA2 is highly expressed in cervical cancer and negatively correlated with cisplatin‐induced cell death. We performed liquid chromatography‐tandem mass spectrometry to demonstrate that HMGA2 has high potential to interact with casein kinase II A1 (CSNK2A1). Moreover, we observed that HMGA2 co‐localizes with CSNK2A1 in the nucleus by immunofluorescence. Binding of HMGA2‐CSNK2A1 was detected by immunoprecipitation assays. In addition, we identified that cisplatin induces an interaction between CSNK2A1 and HMGA2, thereby promoting the phosphorylation of HMGA2. CX‐4945, a CSNK2A1 inhibitor, could inhibit the phosphorylation of HMGA2 and sensitize tumor cells to cisplatin. Our results reveal that CSNK2A1‐dependent HMGA2 phosphorylation may partially underlie cisplatin‐resistance in cervical cancer, suggesting that HMGA2 phosphorylation may have potential as a predicative biomarker and therapeutic target to improve chemotherapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background & Aims: The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non‐Asians, but little is known regarding the effect of ethnicity on outcomes of HBV‐related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non‐Asian patients with HBV‐related HCC. Methods: We analyzed the baseline characteristics and long‐term survival of 613 Asian and 410 non‐Asian patients with HBV‐related HCC from three US and one Spanish centre. Results: Overall, non‐Asian patients were more likely to have HIV or hepatitis C co‐infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P ≤.04). Compared with Asians, non‐Asians were more likely to be listed for transplantation (P <.0001) and undergo HCC treatment with curative intent (P =.003). Propensity‐score matching on HCC diagnosis year, gender and age was performed to balance the two groups for survival analysis and yielded 370 pairs of patients. There was no significant difference in survival overall (P =.43) and among patients with cirrhosis (P =.57). Among patients without cirrhosis, non‐Asians had poorer 5‐year survival compared with Asians (37.6% vs 53.7%, P =.01), and was associated with poorer survival after adjusting for age, gender, diabetes, alcohol, co‐infections, diagnosis date, antiviral therapy, BCLC stage and HCC treatment (adjusted HR 2.01 [95% CI 1.07‐3.74], P =.03). Conclusion: Among HBV‐related HCC patients, non‐Asians presented with more advanced BCLC stage compared to Asians. Non‐Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity. [ABSTRACT FROM AUTHOR]

Intracellular interactions between protein kinases and metabotropic receptors in the striatum regulate behavioral changes in response to drug exposure. We investigated the difference in the degree of interaction between extracellular signal-regulated kinase (ERK) and metabotropic glutamate receptor subtype 5 (mGluR5) in the nucleus accumbens (NAc) after repeated exposure to nicotine in adult and adolescent rats. The results showed that repeated exposure to nicotine (0.5 mg/kg/day, s.c.) for seven consecutive days increased ERK phosphorylation more in adults than in adolescents. Furthermore, membrane expression of mGluR5 in gamma-aminobutyric acid (GABA) medium spiny neurons was higher in adults than adolescents as a result of repeated exposure to nicotine. Blockade of mGluR5 with MPEP (0.5 nmol/side) decreased the repeated nicotine-induced increase in ERK phosphorylation. Either blockade of mGluR5 or inhibition of ERK with SL327 (150 nmol/side) decreased the repeated nicotine-induced increase in the level of inositol-1,4,5-triphosphate (IP3 ), a key transducer associated with mGluR5-coupled signaling cascades. Similarly, interference of binding between activated ERK and mGluR5 by the blocking peptide, Tat-mGluR5-i (2 nmol/side), decreased the repeated nicotine-induced increases in IP3 and locomotor activity in adults. These findings suggest that the intracellular interaction between ERK and mGluR5 in the NAc is stronger in adult than in adolescent rats, which enhances the understanding of age-associated behavioral changes that occur after repeated exposure to nicotine. [ABSTRACT FROM AUTHOR]

In order to improve the dispersion and compatibility of the hydroxyl silicates (HNSs) in organic resin matrix, the HNSs were first functionalized by N‐(2‐aminoethyl)‐3‐aminopropyltrimethoxysilane (KH‐792) via a hydrolysis process; thus, the imino and amidogen groups can be grafted on the surface of HNSs (NH2‐HNSs). Fourier transform infrared spectroscopy, scanning electron microscopy, and X‐ray photoelectron spectroscopy are employed to characterize the chemical structure and surface morphology changes on the surface of HNSs after modified. The modified NH2‐HNSs were then used as fillers to add into bismaleimide (BMI) to prepare the new NH2‐HNSs/BMI composites. The influences of NH2‐HNSs content on the mechanical, tribological, and thermal properties of BMI resin were also researched. The results showed that adding NH2‐HNSs with appropriate content (6.0 wt%) could significantly improve the comprehensive properties of the NH2‐HNSs/BMI composites. It can be observed from the scanning electron microscopy (SEM) on the wear surface of the materials that, the wear mechanism of the BMI resin was converted from adhesive wear to abrasive wear after the addition of NH2‐HNSs. The improvement of tribological and mechanical properties can be mainly attributed to the chemical reaction between BMI and NH2‐HNSs. [ABSTRACT FROM AUTHOR]

A calix[4]pyrrole (1) strapped with a naphthobipyrrole was prepared and its ability to bind the bicarbonate anion (HCO3−) was investigated via 1H NMR and UV/Vis spectroscopic analyses. The resulting spectral data revealed that receptor 1 was capable of recognizing HCO3− with high affinity in solutions as well as in the solid state. In CD2Cl2, it was inferred from 1H NMR spectroscopic titration experiment that HCO3− interacts with receptor 1 via two different modes with the first involving HCO3− being hydrogen bonded to all six NH protons of the receptor. This interaction is followed by a deprotonation process of the bipyrrole NHs upon the subsequent addition of HCO3− while the anion remains hydrogen‐bonded to the calix[4]pyrrole NHs. In the presence of methanol, the bound bicarbonate anion was converted into an unstable monomethyl carbonate anion (CH3OCO2−) that was then stabilized by forming a complex with receptor 1. [ABSTRACT FROM AUTHOR]

Rock slopes with weak intercalated layers could experience disturbance from various deep mining activities; however, their dynamic stability has not been thoroughly investigated. In this paper, the dynamic response characteristics and failure mechanism of the coal slopes with weak intercalated layers under blasting loads were studied by means of numerical analysis, shaking table tests, and field tests. The effects of dynamic loads with different frequencies on the dynamic response of the slope were analyzed, and the natural frequency of the slope was also determined. The results show that the dynamic amplification effect of the slope is smaller than that of the homogeneous slope, and weak layers weaken the wave propagation in the rock mass. Both experimental and field investigation results show that the slope's natural frequency was approximately 35 Hz. The slope deformation decreased with the distance of the blasting source. Cracks appear along the weak interlayer firstly under the action of horizontal vibration; then, longitudinal cracks occur at the slope crest. With the increase of dynamic loads, cracks continue expanding, deepening, and penetrating in the main controlled weak interlayer; then, the sliding body presents tensile shear failure along the sliding surface. This study could provide insights into the understanding of the coal slope instability and failure mechanism; this could benefit the blasting operation of the coal slope in fields. [ABSTRACT FROM AUTHOR]

In this study, we reported the inhibition profiles of 4′‐acylpyrrole–5‐fluoroindolin‐2‐one 3 with a C‐3′ side chain for VEGFR2, PDGFR‐β, and FGFR‐1 protein kinases. The pyrrole‐fused cyclohexanone moiety provided 3 with the best potency to inhibit the three kinases, and the C‐3′ side chains contributed to the different inhibition profiles of 3. Compound 3b with a C‐3′ 2‐carboxylethyl side chain showed good potency for the three kinase (IC50: 25–260 nM), and compound 3g with a N,N‐dialkyl‐2‐carbamoylethyl side chain was more active for VEGFR2 (IC50: 59 nM) and PDGFR‐β (IC50: 16 nM) than FGFR‐1 (IC50: 1.7 μM). The C‐3′ 3‐(dialkylamino)propyl side chain accomplished 3h–j as selective PDGFR‐β inhibitors (IC50: 7.8–13 nM). Compound 3b was further investigated and found potent to inhibit VEGF‐ and FGF‐dependent cell proliferation with moderate in vivo anticancer activity. Results from docking simulations revealed that the interactions of 3b with VEGFR2 and FGFR‐1 which could account for the different inhibition profiles of 3. [ABSTRACT FROM AUTHOR]

A novel chiral 1,5‐N,N‐bidentate ligand based on a spirocyclic pyrrolidine oxazoline backbone was designed and prepared, and it coordinates CuBr in situ to form an unprecedented catalyst that enables efficient oxidative cross‐coupling of 2‐naphthols. Air serves as an external oxidant and generates a series of C1‐symmetric chiral BINOL derivatives with high enantioselectivity (up to 99 % ee) and good yield (up to 87 %). This approach is tolerant of a broader substrates scope, particularly substrates bearing various 3‐ and 3′‐substituents. A preliminary investigation using one of the obtained C1‐symmetric BINOL products was used as an organocatalyst, exhibiting better enantioselectivity than the previously reported organocatalyst, for the asymmetric α‐alkylation of amino esters. [ABSTRACT FROM AUTHOR]

This study aims to investigate the molecular phylogenetic analysis, morphological variability, nematode‐capturing ability, and other biological properties of Chinese Duddingtonia flagrans isolates. We isolated 13 isolates of D. flagrans and found features that have never been reported before, such as two to three septa incluing club‐shaped conidia. Meanwhile, we conducted molecular phylogenetic analysis of the seven isolates and tested the radical growth of the isolates under different pH values, temperatures, and media. The capturing ability against infective larvae (L3) of Cooperia spp. in yak was detected in vitro. Finally, one isolate was selected for scanning electron microscopy (SEM) to investigate the trap formation process. The fungal sequence was obtained and submitted to GenBank (Accession no. KY288614.1, KU881774.1, KP257593.1, KY419119.1, MF488979.1, MF488980.1, and MF488981.1), and the tested isolates were identified as D. flagrans. Except for three isolates, the radial growth of the other isolates on 2% corn meal agar and 2% water agar exhibited faster growth than on other media. The fungus could not grow at 10 and 40°C but grew within 11 to 30°C. Moreover, it did not grow at pH 1–3 and 13–14, but instead at pH 4–12. In the in vitro experimental, L3s were reduced by 94.36%, 88.15%, and 91.04% for SDH035, DH055, and F088, respectively. SEM results showed that at 8 hr post addition of nematodes, some of the latter were captured. In the later stages of the interaction of the fungus with nematodes, a large number of chlamydospores were produced, especially on the predation trap. Results of the present study provided information about the molecular phylogenetic analysis, morphological variability, nematode‐capturing ability, and other biological properties of Chinese Arthrobotrys flagrans isolates before administering them for biocontrol. [ABSTRACT FROM AUTHOR]

Summary: The World Health Organization has set the goal of reducing the hepatitis‐related mortality rate by 65% between 2015 and 2030. Diagnosis and awareness of infection is the first essential step towards achieving this goal. Our study examined the current awareness rate of chronic viral hepatitis in the United States and the potentially associated factors. In the National Health Nutrition and Examination Survey 2013‐2016, there were 11 488 persons who participated in serology testing for chronic viral hepatitis. We defined chronic hepatitis B virus (HBV) infection by HbsAg, HBV past exposure by anti‐HBc and hepatitis C virus (HCV) infection by HCV RNA. At risk for significant fibrosis was determined by AST to Platelet Ratio Index >0.7. Awareness of chronic HBV infection, past HBV exposure and HCV infection were present in 33.9%, 11.7% and 55.6% of participants, respectively. Among HCV‐infected baby boomers, the awareness was in 61.5%. The awareness of HBV infection was significantly higher in individuals with high education level. Age group (40‐60 years), women, non‐Black race/ethnicity and those with high household income who were born in the United States with insurance plans tend to be aware of their infection. For HCV, awareness was the lowest in Hispanics and Asians, foreign‐born who lived below the federal poverty level and low education level. Awareness among chronic viral hepatitis patients at risk for significant fibrosis was 62.0% in HBV and 38.2% in HCV infection. In conclusion, current awareness of chronic viral hepatitis in the United States remains suboptimal. Active public health policy to identify persons at risk and provide appropriate management is warranted. [ABSTRACT FROM AUTHOR]

Background and Aim: Percutaneous cholecystostomy (PC) has been frequently used as an alternative treatment for acute cholecystitis in seriously ill patients unfit for surgery. The aim of this study was to investigate the recurrence rate and risk factors of recurrence. Methods: Medical records of 102 patients who were followed up for more than 1 year after PC tube removal among 716 patients who underwent PC for acute cholecystitis treatment were retrospectively analyzed. Results: The recurrence rate of acute cholecystitis after PC tube removal was 20.6% (21/102), and the mean time to recur was 660 days. Underlying cancer (odds ratio [OR]: 3.369; 95% confidence interval [CI]: 1.006–11.282; P = 0.0489), PC duration shorter than 44 days (OR: 5.596; 95% CI: 1.35–23.201; P = 0.0176), and the presence of common bile duct stone in initial imaging studies (OR: 24.393; 95% CI: 2.696–220.746; P = 0.0045) were positively correlated with recurrence. Tubogram before PC tube removal did not significantly lower the recurrence. However, PC tube clamping for several days significantly lowered the recurrence (OR: 0.108; 95% CI: 0.015–0.794; P = 0.0288). Fifty‐nine (57.8%) had acalculous cholecystitis. Calculous cholecystitis was negatively correlated with recurrence (OR: 0.267; 95% CI: 0.074–0.967; P = 0.0444). Receiver operating characteristic curve of the prediction model for recurrence verified its accuracy (area under the curve: 0.8475). Conclusion: We should try to keep PC more than 6 weeks and clamp for 1–2 weeks before removal. For those with the presence of common bile duct stones, calculous cholecystitis, and underlying malignancy, we should keep PC for longer duration and carefully observe symptoms and signs of recurrence. [ABSTRACT FROM AUTHOR]

B ackground/Aims: Hypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC. Materials and Methods: We retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid‐stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence‐free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results. Results: A total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44‐4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses. Conclusion: Hypothyroidism is associated with poorer overall and recurrence‐free survival of HCC patients receiving liver transplantation. These results require validation. Hypothyroidism has been reported to be associated with hepatocellular carcinoma (HCC) incidence, and this conclusion was also supported by basic experiments. However, no study has yet reported the relationship between hypothyroidism and the outcome of HCC. We identified hypothyroidism as an independent risk factor for overall survival of HCC patients treated by liver transplantation. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is one inflammatory bowel disease (IBD) and is caused by diverse factors, including the extent and duration of intestinal inflammation. We investigated the effect of Acer palmatum thumb. ethanol extract (KIOM-2015E) on the expression of tight junction proteins and the levels of inflammation in the cell model induced with interleukin-6- (IL-6-) and mouse model of dextran sodium sulfate (DSS) induced with acute colitis. KIOM-2015E (100 mg/kg) was orally administered once per day to BALB/C mice with colitis induced by administration of 5% DSS in drinking water. KIOM-2015E did not affect viability in Caco-2 cells. Also, KIOM-2015E repaired the IL-6-induced intestinal barrier dysfunction in Caco-2 cells. Furthermore, KIOM-2015E recovered the loss of body weight and the abnormally short colon lengths in the DSS-induced model of acute colitis. Moreover, KIOM-2015E significantly inhibited the decrease of zonula occluden-1 and occludin in colonic tissue relative to the DSS-treated control group. KIOM-2015E also significantly inhibited the expression of IL-6 and tumor necrosis factor-α in the level of serum relative to the control group. Collectively, these data suggest that KIOM-2015E protects colitis principally by improving intestinal barrier function and promoting anti-inflammatory responses. In turn, these effects inhibit macrophage infiltration into the colon and thus may be a candidate treatment for IBD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Variants in TMC1 (transmembrane channel‐like 1) can cause both autosomal dominant and recessive hearing loss in human population. Mice with Tmc1 variants have been shown to be ideal animal models for gene therapy. In this article, we report four TMC1 variants in four different Chinese families and the follow‐up auditory phenotype of a previously reported family. Methods: Four families with TMC1 variants, as well as a previously described family with TMC1 variant orthologous to the Beethoven mouse, were recruited in this study. A comprehensive auditory evaluation was performed on all ascertained family members. High‐throughput sequencing was conducted using genomic DNA from the probands and other family members to identify probable deafness genes. Results: We identified four TMC1 (NM_138691.2) variations, including two pathogenic variants, c.1714G>A, and c.1253T>A, one likely pathogenic variant, c.[797T>C];[797T>C], and one single nucleotide polymorphism (SNP), c.2276G>A. Among these variants, c.[797T>C];[797T>C] is a novel likely pathogenic variant, and c.1714G>A and c.1253T>A are known pathogenic variants at the DFNB7/11 (DFNA36) locus. Phenotype‐genotype correlation analysis of TMC1 variants showed that the TMC1 dominant variation‐related phenotype was late‐onset, progressive, high frequency to all frequency sensorineural hearing loss, while the TMC1 recessive variant was related to congenital all frequency sensorineural hearing impairment. Conclusions: Two pathogenic, one likely pathogenic variants and one SNP of TMC1 were identified in four Chinese families with hereditary hearing loss, indicating that TMC1 may be a more frequent cause of hearing loss than expected. TMC1 variants related to hearing loss result in specific phenotypes. The TMC1 c.1253T>A (p.M418K) variation, homologous to the Tmc1 c. 1235 T> A (p.M412K) variant in Beethoven mice, was the second report of this variant in human patients with hearing loss, suggesting the possibility to translational gene therapy from Beethoven mice to human patients. [ABSTRACT FROM AUTHOR]

Abstract: Hepcidin is crucial in regulating iron metabolism, and increased serum levels were strongly linked with poor outcomes in various malignancies. Thus, we investigated if genetic variants in the BMP/Smad4/Hamp hepcidin‐regulating pathway were associated with outcomes in patients receiving definitive radiotherapy for NSCLC. Subjects were 664 NSCLC patients who received ≥60 Gy radiotherapy for NSCLC retrospectively identified from a single‐institution database. Potentially, functional and tagging single nucleotide polymorphisms (SNPs) of BMP2 (rs170986, rs1979855, rs1980499, rs235768, and rs3178250), BMP4 (rs17563, rs4898820, and rs762642), Smad4 (rs12456284), and Hamp (rs1882694, rs10402233, rs10421768, and rs12971321) were genotyped by TaqMan real‐time polymerase chain reaction. Cox proportional hazard's analyses were used to assess potential influences of SNPs on overall survival (OS), local‐regional progression‐free survival (LRPFS), progression‐free survival (PFS), and distant metastasis‐free survival (DMFS). Nomogram of each endpoint model was developed using R project. The median patient age was 66 years. Most (488 [73.2%]) had stage III NSCLC. Age, disease stage, receipt of concurrent chemotherapy, and gross tumor volume were independent factors of OS. Hamp rs1882694 AC/CC genotypes were associated with poor OS, LRPFS, PFS, and DMFS in multivariate analyses. Besides, BMP2 rs1979855, rs3178250, and rs1980499 associated with PFS; Hamp rs10402233 and BMP2 rs1979855 associated with LRPFS; BMP2 rs3178250 associated with DMFS after adjustment for clinical factors. After adding SNPs to each model, all the likelihood ratios were increased; the nomograms were improved significantly to predict LRPFS (P < 0.001) and PFS (P < 0.001), and marginally to predict OS (P = 0.056) and DM (P = 0.057). Our nomograms incorporating significant SNPs in the BMP/Smad4/Hamp hepcidin‐regulating pathway could improve the prediction of outcomes in patients given definitive radiotherapy for NSCLC. Intensified follow‐ups would be recommended for patients with unfavorable outcomes identified in nomograms. Due to the rapid developments of targeted therapies and immunotherapies for NSCLC, it is necessary to further validate our findings in patients receiving such treatments. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non‐viral causes of HCC, particularly non‐alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC. Methods: We conducted a retrospective cohort study involving 3878 consecutive HCC patients seen at two tertiary centres in the United States and one in Taiwan from 2004 to 2014. We compared the clinical characteristics, treatment and survival of patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n = 1878). Results: Cirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV‐related HCC (HBV‐HCC) (P = .001) and 85.9% of HCV‐HCC (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumours and at later stages of disease. Five‐year overall survival was 16.3% among cryptogenic HCC patients compared with 31.9% among HBV‐HCC patients and 27.7% among HCV‐HCC patients (P < .001 for both by the log‐rank test). HCC aetiology was not an independent predictor of survival, though ethnicity, cirrhosis status, meeting Milan criteria and treatment allocation were. Conclusions: Compared with viral HCC patients, those with cryptogenic HCC had lower prevalence of cirrhosis, were diagnosed with larger tumours at more advanced stages of disease, and had poorer overall survival. Additional efforts are needed to identify patients at risk of cryptogenic HCC and to identify cryptogenic HCC at earlier stages of disease. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America. Methods: We evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations. Results: Sixty-eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV-related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance, and there was no difference in age of diagnosis between those diagnosed incidentally vs by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (P = .01). Conclusions: Our study represents the largest cohort to date reporting characteristics and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programmes, with associated increased mortality in those patients. [ABSTRACT FROM AUTHOR]

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families, each of which had two affected siblings, were included in this study. The families underwent target region capture and high-throughput sequencing to analyze the exonic, splice-site, and intronic sequences of 128 genes. Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese families segregating with apparent ARNSHL, who had been previously excluded for variants in the common deafness genes GJB2 and SLC26A4, were subjected to screening for candidate mutations. We identified a novel homozygous missense mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the first report to identify PDZD7 as an ARNSHL-associated gene in the Chinese population. Our finding could expand the pathogenic spectrum and strengthens the clinical diagnostic role of the PDZD7 gene in ARNSHL patients. [ABSTRACT FROM AUTHOR]

Davallia mariesii Moore (Drynaria rhizome extract (DRE)) is widely known for its efficacy in treating inflammation, arteriosclerosis, and bone injuries. This study evaluated whether treatment with DRE inhibited FcɛRI-mediated allergic responses in the RBL-2H3 mast cells and investigated the early- and late-phase mechanisms by which DRE exerts its antiallergic effects. IgE anti-DNP/DNP-HSA-sensitized RBL-2H3 mast cells were tested for cytotoxicity to DRE, followed by the assessment of β-hexosaminidase release. We measured the amounts of inflammatory mediators (e.g., histamine, PGD2, TNF-α, IL-4, and IL-6) and examined the expression of genes involved in arachidonate and FcεRI signaling pathways. In addition, we confirmed the antiallergic effects of DRE on passive cutaneous anaphylaxis (PCA) in mice. DRE inhibited RBL-2H3 mast cell degranulation and production of allergic mediators in them. In early allergic responses, DRE reduced expression of FcεRI signaling-related genes (e.g., Syk, Lyn, and Fyn) and extracellular signal-regulated kinase phosphorylation in mast cells. In late allergic responses, DRE reduced PGD2 release and COX-2 expression and cPLA2 phosphorylation in FcɛRI-mediated mast cells. Lastly, 250–500 mg/kg DRE significantly attenuated the IgE-induced PCA reaction in mice. These findings provide novel information on the molecular mechanisms underlying the antiallergic effects of DRE in FcɛRI-mediated allergic responses. [ABSTRACT FROM AUTHOR]

Background: There is global variation in the onset of hepatocellular carcinoma (HCC). The objective of the current study was to investigate the impact of country of birth on age at the time of HCC diagnosis in the United States.Methods: Incident HCC cases diagnosed between 2000 and 2012 in the Surveillance, Epidemiology, and End Results program 18 registry were included. Factors associated with very early onset (age at diagnosis < 40 years) and early onset (age at diagnosis < 50 years) were identified by logistic regression.Results: A total of 59,907 patients were included. The median age at the time of diagnosis of HCC was 62 years and 76% of the patients were male. Of the 75% of patients for whom information regarding birth country was available, 29% were foreign born. In multivariate logistic regression, birth in West Africa (adjusted odds ratio [AOR], 16.3; 95% confidence interval [95% CI], 9.2-27.9 [P<.01]), Central/South/other Africa (AOR, 11.0; 95% CI, 4.5-23.7 [P<.01]), Oceania (AOR, 4.9; 95% CI, 2.9-8.0 [P<.01]), and East Africa (AOR, 3.5; 95% CI, 1.5-6.8 [P<.01]) was found to have the strongest association with very early-onset HCC after adjusting for sex and race/ethnicity. Birth in West Africa, Central/South/other Africa, Oceania, or East Africa also was found to be strongly associated with early-onset HCC.Conclusions: Birth country was found to be independently associated with age at the time of HCC diagnosis in the United States. Birth in Africa (except for North Africa) and Oceania was strongly associated with very early-onset HCC. These findings have implications for the design of comprehensive HCC surveillance programs in the United States. Cancer 2016. © 2016 American Cancer Society. Cancer 2017;81-89. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]