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Background: With the popularity of the internet, short videos have become an indispensable tool to obtain health information. However, avoiding health disinformation owing to the openness of the Internet is difficult for users. Disinformation may endanger the health and lives of users. Objective: With a focus on the process of identifying short videos' health disinformation and the factors affecting the accuracy of identification, this study aimed to investigate the identification methods, coping strategies, and the impact of short videos’ health disinformation on undergraduate nursing students. The findings will provide guidance to users on obtaining high-quality and healthy information, in addition to reducing health risks. Methods: Semi-structured in-depth interviews were conducted with 22 undergraduate nursing students in October 2022, and data were collected for collation and content analyses. Results: The techniques used to identify short videos that include health disinformation as well as how undergraduate nursing students perceived these videos' features are among the study's findings. The failure factors in identification, coping paths, and adverse impacts of short videos on health disinformation were analyzed. The platform, the material itself, and the students' individual characteristics all have an impact on their identifying behavior. Conclusions: Medical students continue to face many obstacles in identifying and responding to health disinformation through short videos. Preventing and stopping health disinformation not only requires individual efforts to improve health literacy and maintain rational thinking, it also requires the joint efforts of short video producers, relevant departments, and platforms.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Background: The predictive value of the methylation of Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and H19 promoters in peripheral blood leukocytes as a non-invasive biomarker for the chemotherapy effect and prognosis gastric cancer (GC) is unclear. Methods: The DNA methylation of H19 and MALAT1 between chemotherapy-sensitive and non-sensitive groups and between groups with better and worse survival of GC was compared using regression analyses. Several predictive nomograms were constructed. The genetic alteration of MALAT1 and H19 and the association between gene expression and immune status in GC were also investigated using bioinformatics analysis. Results: Higher genetic methylations in peripheral blood were noticed in GC groups with poorer survival. The constructed nomograms presented strong predictive values for the chemotherapy effect and 3-year survival of disease-free survival, progression-free survival, and overall survival, with the area under the curve as 0.838, 0.838, 0.912, and 0.925, respectively. Significant correlations between MALAT1 or H19 expression and marker genes of immune checkpoints and immune pathways were noticed. The high infiltration of macrophages in H19-high and low infiltration of CD8+ T cells in MALAT1-high groups were associated with worse survival of GC. Conclusions: MALAT1 and H19 have the potential to predict the chemotherapy response and clinical outcomes of GC.

Background: Murine Nischarin and its human homolog IRAS are scaffold proteins highly expressed in the central nervous system (CNS). Nischarin was initially discovered as a tumor suppressor protein, and recent studies have also explored its potential value in the CNS. Research on IRAS has largely focused on its effect on opioid dependence. Although the role of Nischarin/IRAS in the physiological function and pathological process of the CNS has gradually attracted attention and the related research results are expected to be applied in clinical practice, there is no systematic review of the role and mechanisms of Nischarin/IRAS in the CNS so far. Aim of review: This review will systematically analyze the role and mechanism of Nischarin/IRAS in the CNS, and provide necessary references and possible targets for the treatment of neurological diseases, thereby broadening the direction of Nischarin/IRAS research and facilitating clinical translation. Key scientific concepts of review: The pathophysiological processes affected by dysregulation of Nischarin/IRAS expression in the CNS are mainly introduced, including spinal cord injury (SCI), opioid dependence, anxiety, depression, and autism. The molecular mechanisms such as factors regulating Nischarin/IRAS expression and signal transduction pathways regulated by Nischarin/IRAS are systematically summarized. Finally, the clinical application of Nischarin/IRAS has been prospected.

Summary: Background: This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small–cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Methods: Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4–6 cycles of adebrelimab (20 mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100 mg/m2, D1-3, Q3W and cisplatin, 75 mg/m2, D1, Q3W or carboplatin, AUC = 5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. Findings: From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2–not reached months) and 10.1 months (95% CI: 6.9–15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3–82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7–95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P = 0.071; ctDNA, P = 0.060) and OS (tissue, P = 0.032; ctDNA, P = 0.031). Interpretation: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. Funding: This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

For a directed graph D, it's deemed rainbow connected if each arc is assigned a different color, so that all paths from the vertex u to the vertex v are rainbow connected. Rainbow connection number refers to how many colors are needed in D to achieve rainbow connectivity. Among ordered vertex pair (u,v) with arc coloring, if both arcs and internal vertices exhibit unique colors, it is referred to as a total colored graph. As the total rainbow connection number indicates, the smallest number of colors are required to total-color D. This paper focuses on investigating the rainbow connection number of the biorientation of a connected graph, as well as the total rainbow connection number.

Uniportal video-assisted thoracoscopic surgery (UVATS) segmentectomy has emerged as an effective approach for managing early-stage non-small-cell lung cancer (NSCLC). Compared to conventional open and thoracoscopic surgeries, this minimally invasive surgical technique offers multiple benefits, including reduced postoperative discomfort, shorter hospital stays, expedited recovery, fewer complications, and superior cosmetic outcomes. Particularly advantageous in preserving lung function, UVATS segmentectomy is a compelling option for patients with compromised lung capabilities or limited pulmonary reserve. Notably, it demonstrates promising oncological results in early-stage NSCLC, with long-term survival rates comparable to those of lobectomies. Skilled thoracic surgeons can ensure a safe and effective execution of UVATS despite the potential technical challenges posed by complex tumor locations that may hinder visibility and maneuverability within the thoracic cavity. This study provided a comprehensive review of the literature and existing studies on UVATS segmentectomies. It delves into the evolution of the technique, its current applications, and the balance between its benefits and limitations. This discussion extends the technical considerations, challenges, and prospects of UVATS segmentectomy. Furthermore, it aimed to update advancements in segmentectomy for treating early-stage NSCLC, offering in-depth insights to thoracic surgeons to inform more scientifically grounded and patient-specific surgical decisions.

Pulmonary mucinous adenocarcinoma (PMA), a distinct subtype of non-small cell lung cancer (NSCLC), is characterized by an abundance of mucin-producing cells. Although this subtype comprises a relatively small fraction of lung adenocarcinomas, PMA stands apart due to its unique clinical, pathological, and molecular features. This review comprehensively discusses the pathophysiology and etiology, clinical features, diagnostic methods, treatment strategies, prognosis, and future directions for PMA, drawing from relevant literature and existing studies. Advances in PMA treatment includes surgical intervention, targeted therapy, immunotherapy, and adjuvant therapy. Particularly, we discussed factors influencing the prognosis of PMAs, such as molecular markers, pathological features, and the impact of the latest treatment advances on prognosis. Moreover, we intended this review to be a comprehensive reference for diagnosing, treating, and assessing the prognosis of PMA, providing valuable guidance for clinical practice.

Background: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. Methods: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. Results: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01–10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. Conclusions: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

Objectives: To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer’s disease (AD) continuum. Design: A longitudinal, observational cohort study. Setting: Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. Participants: Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months’ follow-up. Measurements: The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. Results: Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (β = −1.317, P = 0.003), affective symptoms (β = −1.887, P < 0.001), and appetite/eating disorders (β = −1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (β = −0.048), affective symptoms (β = −0.181), and appetite/eating disorders (β = −0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. Conclusions: We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

Once China’s Tianwen-1 Mars probe arrived in a Mars orbit after a seven-month flight in the deep cold space environment, it would be urgently necessary to monitor its state and the surrounding environment. To address this issue, we developed a flexible deployable subsystem based on shape memory polymer composites (SMPC-FDS) with a large folding ratio, which incorporates a camera and two temperature telemetry points for monitoring the local state of the Mars orbiter and the deep space environment. Here, we report on the development, testing, and successful application of the SMPC-FDS. Before reaching its Mars remote-sensing orbit, the SMPC-FDS is designed to be in a folded state with high stiffness; after reaching orbit, it is in a deployed state with a large envelope. The transition from the folded state to the deployed state is achieved by electrically heating the shape memory polymer composites (SMPCs); during this process, the camera on the SMPC-FDS can capture the local state of the orbiter from multiple angles. Moreover, temperature telemetry points on the SMPC-FDS provide feedback on the environment temperature and the temperature change of the SMPCs during the energization process. By simulating a Mars on-orbit space environment, the engineering reliability of the SMPC-FDS was comprehensively verified in terms of the material properties, structural dynamic performance, and thermal vacuum deployment feasibility. Since the launch of Tianwen-1 on 23 July 2020, scientific data on the temperature environment around Tianwen-1 has been successfully acquired from the telemetry points on the SMPC-FDS, and the local state of the orbiter has been photographed in orbit, showing the national flag of China fixed on the orbiter.

Metal-polymer composite components are widely used in aerospace, automotive, and other industries as lightweight composite parts that can result in significant weight savings. Injection-molded direct joining (IMDJ) technology has a broad application prospect for achieving a close connection between metal and polymer without destroying the metal matrix. This study subjected the titanium alloy surface to sandblasting, anodizing, etching, and annealing, resulting in uniformly distributed claw-like nanostructures generated on the surface. This treatment also improved the surface roughness, exhibiting excellent wettability with a contact angle of only 10.7°. The injection-molded direct joining technique was employed to join Ti alloy and polyphenylene sulfide (PPS) composite components. Tensile testing revealed a bond strength of 33.5 MPa, and analysis of the peeled specimens' residual elements indicated that failure of the composite components occurred in the form of polymer cohesion damage, showcasing excellent bonding effects.

Objective: Numerous studies have highlighted the role of clock genes in diabetes disease and pancreatic β cell functions. However, whether rhythmic long non-coding RNAs involve in this process is unknown. Methods: RNA-seq and 3’ rapid amplification of cDNA ends (RACE)-PCR were used to identify the rat LncCplx2 in pancreatic β cells. The subcellular analysis with qRT-PCR and RNA-Scope were used to assess the localization of LncCplx2. The effects of LncCplx2 overexpression or knockout (KO) on the regulation of pancreatic β cell functions were assessed in vitro and in vivo. RNA-seq, immunoblotting (IB), Immunoprecipitation (IP), RNA pull-down, and chromatin immunoprecipitation (ChIP)-PCR assays were employed to explore the regulatory mechanisms through LncRNA-protein interaction. Metabolism cage was used to measure the circadian behaviors. Results: We first demonstrate that LncCplx2 is a conserved nuclear long non-coding RNA and enriched in pancreatic islets, which is driven by core clock transcription factor BMAL1. LncCplx2 is downregulated in the diabetic islets and repressed by high glucose, which regulates the insulin secretion in vitro and ex vivo. Furthermore, LncCplx2 KO mice exhibit diabetic phenotypes, such as high blood glucose and impaired glucose tolerance. Notably, LncCplx2 deficiency has significant effects on circadian behavior, including prolonged period duration, decreased locomotor activity, and reduced metabolic rates. Mechanistically, LncCplx2 recruits EZH2, a core subunit of polycomb repression complex 2 (PRC2), to the promoter of target genes, thereby silencing circadian gene expression, which leads to phase shifts and amplitude changes in insulin secretion and cell cycle genes. Conclusions: Our results propose LncCplx2 as an unanticipated transcriptional regulator in a circadian system and suggest a more integral mechanism for the coordination of circadian rhythms and glucose homeostasis.

Extracting polyphenolic bioactive compounds from Pinus elliottii needles, a forestry residue, promises economic and environmental benefits, however, relevant experimental data are lacking. Herein, a comprehensive investigation of the polyphenolic composition of pine needles (PNs) was carried out. Ultrasound-Assisted Extraction (UAE) was applied to extract the polyphenolic compounds of pine needles. The optimal conditions of extracts were determined by Response Surface Methodology (RSM). The maximum total phenolic content (TPC) of 40.37 mg GAE/g PNs was achieved with solid–liquid ratio of 1:20, 60 % ethanol, and 350 W for 25 min at 45 °C. Polyphenolic extracts showed antioxidant activity in scavenging free radicals and reducing power (DPPH, IC50 41.05 μg/mL; FRAP 1.09 mM Fe2+/g PNs; ABTS, IC50 214.07 μg/mL). Furthermore, the second-order kinetic model was also constructed to describe the mechanism of the UAE process, with the extraction activation energy estimated at 12.26 kJ/mol. In addition, 37 compounds in PNs were first identified by UHPLC-Q-Exactive Orbitrap MS/MS, including flavonoids and phenolic acids. The results suggest that Ultrasound-Assisted is an effective method for the extraction of natural polyphenolic compounds from pine needles and this study could serve as a foundation for utilizing phenolics derived from PNs in the food and pharmaceutical industries.

Study region: Shenzhen Bay (SZB) in the east Pearl River Estuary, China Study focus: Either NO3− or NH4+ is the dominant component of dissolved inorganic nitrogen (DIN) in most estuarine waters, but few studies focused on the mechanisms of ongoing DIN transformations under various hydrologic regimes. This analysis spans 31 years of DIN component changes and involves numerical simulations to identify the roles of various driving factors including runoff and biogeochemical actions. These new insights into DIN change mechanisms from the coupling biogeochemical and hydrodynamic processes would help to boost effective mitigation measures to deal with nitrate accumulation in estuarine waters, thereby supporting integrated land-ocean nutrient management. New hydrological insights for the region: The dominant DIN component in the SZB was found to transition from NH4+ to NO3− between 1990 and 2020. Particularly in the -upper bay, there was an unexpected increase in the mean concentration fraction of NO3− in DIN, rising from 19.5% (1990‐2017) to 65.5% (2018‐2020). This change can be partially attributed to reduced runoff NH4+ inputs. Both runoff and tidal current can transport NH4+ and NO3−downstream, but the high background levels of NO3− in the lower bay contributed to sustaining NO3− in the upper bay through ebb and flow. Biogeochemical actions further strengthened the decline of NH4+ and the rise of NO3−. Even in scenarios without terrestrial source inputs, the simulated biogeochemical processes continued to help reduce NH4+ levels throughout the bay while increasing NO3− concentrations in the middle and lower bay.

It is of great significance for the optimization of transportation strategy to study the methods of energy shipping scheduling. Based on the Hopfield neural network (HNN) theory, this paper proposes Hopfield neural network energy transportation path optimization algorithm with improved activation function, which solves the problems of poor mapping ability, low flexibility and high sensitivity of neurons near zero to input of traditional activation function. The improved activation function can reduce the derivative value of the activation function and the sensitivity of neurons near zero to the input value by flexibly adjusting the steepness, positioning and mapping range of energy sea transportation at the same time. The experimental results show that: under the same initial conditions, the model proposed in this paper shows better error code performance, and the data length of the required transmission sequence is shorter. When sending 8PSK (Phase Shift Keying) signal with a data length of N = 40, the error rate of the 2-path synthesized random channel is less than 0.112. The error code performance and convergence speed of the energy shipping path planning algorithm are improved effectively.

Introduction: Triterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown. Objectives: This work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus. Methods: Two OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif. Results: AmOSC2 is a β-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of β-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for β-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role. Conclusion: The study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Background: The study aimed to identify the relations of the absolute lymphocyte count (ALC) nadir during prophylactic cranial irradiation (PCI) and patient outcomes in limited-stage small cell lung cancer (LS-SCLC). Methods: We analyzed 268 L S-SCLC patients who underwent PCI from 2012 to 2019. ALC values were collected prior, during, and 3 months post PCI. Kaplan–Meier and Cox regression analyses were performed to assess the relation of ALC to patient prognosis. Two nomograms were developed on the basis of clinical variables for survival prediction. Results: Compared with the ALC before PCI (1.13 × 109 cells/L), the ALC nadir during PCI was significantly reduced by 0.68 × 109 cells/L (P

Dysregulated microRNA (miRNA) expression in the brain can contribute to cognitive dysfunction and aberrant tau hyperphosphorylation in Alzheimer’s disease (AD). Several studies have reported a role for microRNA-23b-3p (miR-23b-3p) in various neurologic disorders; however, its involvement in cognition-related functions remains unclear. In the present study, we investigated the potential therapeutic effects and mechanisms of miR-23b-3p in AD. miRNA profiles in the cortex of amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice (APP/PS1 mice) demonstrated that miR-23b-3p was reduced. This decrease was verified in APPswe cells, SAMP8 mouse brains, and plasma from AD patients. Furthermore, glycogen synthase kinase-3β (GSK-3β), a major tau kinase implicated in tau pathology, was identified as a target of miR-23b-3p. Functional in vivo studies demonstrated that intracerebroventricular delivery of miR-23b-3p in APP/PS1 mice ameliorated cognitive deficits, histopathological changes, and tau phosphorylation immunoreactivity at several sites by inhibiting GSK-3β expression and activation. Similarly, the upregulation of miR-23b-3p in APPswe cells inhibited GSK-3β-mediated tau hyperphosphorylation, Aβ1-42 generation, and neuronal apoptosis, resulting in the suppression of the GSK-3β/p-tau and Bax/caspase-3 pathways. Collectively, our findings strongly support the hypothesis that miR-23b-3p plays a neuroprotective role in AD, thereby identifying miR-23b-3p as a promising therapeutic target for AD.

Critics decry cryptocurrency mining as a huge waste of energy, while proponents insist on claiming that it is a green industry. Is Bitcoin mining really worth the energy it consumes? The high power consumption of cryptocurrency mining has become the latest global flashpoint. In this paper, we define the Mining Domestic Production (MDP) as a method to account for the final outcome of the Bitcoin mining industry’s production activities in a certain period time, calculate the carbon emission per unit output value of the Bitcoin mining industry in China, and compare it with three other traditional industries. The results show that Bitcoin mining does not always have the highest when compared with others. The contribution of this paper is that we give a new perspective on thinking whether Bitcoin mining is more efficient to make more profit, in terms of the same amount of carbon emissions per unit compared to other industries. Moreover, it could even be argued that Bitcoin may present an opportunity for some developing countries to build out their electrical capacity and generate revenue.

Existing studies have revealed that microRNAs (miRNAs) have a role in cognitive deficits in Alzheimer’s disease (AD). However, the function and pathophysiological mechanism of deregulated miRNAs underlying AD pathology remain to be investigated. The present study aimed to clarify the role and mechanism of miR-148a-3p in AD. RNA sequencing, qRT-PCR, and western blot analysis were used to identify the aberrant expression and signaling of miR-148a-3p within cells, mice, and patients with AD. Molecular biology techniques involving luciferase reporter assays, gene overexpression and silencing, chromatin immunoprecipitation, and adeno-associated virus-based miRNA overexpression were used to explore the biological function and mechanisms of miR-148a-3p. Downregulation of miR-148a-3p was identified in AD. Upregulation of miR-148a-3p was found to protect neuronal cells against Aβ-associated tau hyperphosphorylation by directly targeting p35/CDK5 and PTEN/p38 mitogen-activated protein kinase (MAPK) pathways. A mutual regulatory link between miR-148a-3p and PTEN using a feedforward arrangement was confirmed via promotion of transcription and expression of miR-148a-3p by way of the PTEN/Akt/CREB pathway. Significantly, in vivo targeting of miR-148a-3p signaling ameliorated cognitive deficits by decreasing p35/PTEN-elicited tau hyperphosphorylation, accompanied by feedforward transduction of the PTEN/Akt/CREB pathway. In conclusion, the present study implicated the miR-148a-3p/p35/PTEN pathway as an essential contributor to tau hyperphosphorylation and feedforward regulation in AD.

Background: The coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to the treatment of lung cancer patients. Materials and methods: The PubMed, Embase, and Web of Science databases were searched for studies published before March 15, 2022, and Stata 14.0 software was used to perform a meta-analysis with a random-effects model. The odds ratio (OR) along with the corresponding 95% confidence interval (CI) was reported. Results: Our meta-analysis included 80 articles with 318,352 patients involved. The proportion of lung cancer patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 2.4% (95% CI: 0.02–0.03) prior to the Omicron variant outbreak. Among COVID-19 patients, those with lung cancer showed a higher mortality rate than those with other types of malignant solid tumors (OR = 1.82, 95% CI: 1.61–2.06) and non-cancer patients (OR = 4.67, 95% CI: 3.61–6.05); however, no significant difference was observed in the mortality rate between patients with lung cancer and those with hematologic malignancies (OR = 1.07, 95% CI: 0.85–1.33). SARS-CoV-2 infection significantly increased the mortality rate in lung cancer patients (OR = 8.94, 95% CI: 6.50–12.31). By contrast, the all-cause mortality rate in lung cancer patients (OR = 1.04, 95% CI: 0.69–1.57) and the proportion of patients diagnosed with advanced lung cancer (OR = 1.04, 95% CI: 0.85–1.27) did not significantly change before and after the pandemic. Conclusions: More attention should be paid on improving the health of lung cancer patients during the COVID-19 pandemic.

Background: Few studies have examined the effect of ambient temperature on upper urolithiasis in developing countries, with even fewer considering individual factors. Methods: The present study analyzed data on emergency department visits for upper urolithiasis from three hospital sites of a large hospital in Hefei, China, during 2016–2020. Data on environmental factors during the same period were also analyzed. A time series analysis employing a generalized Poisson regression model (GPRM) combined with a distributed lag non-linear model (DLNM) was conducted to evaluate the effect of ambient temperature on the number of emergency department visits for upper urolithiasis. Results: We found that ambient temperatures above 9 °C were positively associated with the frequency of upper urolithiasis visits, with the relationship being most significant on the current day and with a one-day lag. In the single-day lag effect, the most significant relative risk (RR) for mild heat (75th percentile) and high heat (95th percentile) was 1.229 (95% CI: 1.100–1.373) and 1.337 (95% CI: 1.134–1.577), respectively. The cumulative lag effect was significantly higher than the single-day lag effect, with maximum relative risks (RRs) of 1.779 (95% CI: 1.356–2.335) and 2.498 (95% CI: 1.688–3.697), respectively. The maximum lag time was 7 days. RRs were also higher among women and individuals aged 30–44 years. Conclusions: Increased ambient temperature is a risk factor for upper urolithiasis, and there is a hysteresis effect. Women and individuals aged 30–44 years are the most susceptible.

Summary: Background: As aortic aneurysms (AAs) enlarge, they can become life-threatening if left undiagnosed or neglected. At present, there is a lack of radical treatments for preventing disease progression. Therefore, we aimed to identify effective drug targets that slow the progression of AAs. Methods: A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets which are associated with AAs. Summary statistics for AAs were obtained from two datasets: the UK Biobank (2228 cases and 408,565 controls) and the FinnGen study (3658 cases and 244,907 controls). Cis-expression quantitative trait loci (cis-eQTL) for druggable genes were retrieved from the eQTLGen Consortium and used as genetic instrumental variables. Colocalization analysis was performed to determine the probability that single nucleotide polymorphisms (SNPs) associated with AAs and eQTL shared causal genetic variants. Findings: Four drug targets (BTN3A1, FASN, PLAU, and PSMA4) showed significant MR results in two independent datasets. Proteasome 20S subunit alpha 4 (PSMA4) and plasminogen activator, urokinase (PLAU) in particular, were found to have strong evidence for colocalization with AAs, and abdominal aortic aneurysm in particular. Additionally, except for the association between PSMA4 and intracranial aneurysms, no association between genetically proxied inhibition of PLAU and PSMA4 was detected in increasing the risk of other cardiometabolic risks and diseases. Interpretation: This study supports that drug-targeting PLAU and PSMA4 inhibition may reduce the risk of AAs. Funding: This work was supported by National Key R&D Program of China (NO. 2017YFC0909400), Nature Science Foundation of China (No. 91839302, 81790624), Project supported by Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01), and Tongji Hospital Clinical Research Flagship Program (no. 2019CR207).

Objective: To assess the feasibility of dose escalation guided by 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) for esophageal cancer (EC). Methods and materials: Ten random patients treated with definitive chemoradiotherapy and pre-therapeutic 18F-FDG PET/CT were included in this study. Retrospectively, a threshold of 50% of SUVmax was used to define the high FDG uptake region of the GTV (GTVPET). Three intensity-modulated radiation therapy (IMRT) plans were generated, delivering three dose levels to three different planning target volumes (PTVs). 50.4 ​Gy delivered to PTV50.4 was defined on computed tomography (CT) as Plan50.4, 63 ​Gy was delivered to PTV63 was defined as GTV plus a uniform margin of 0.5 ​cm as Plan63, and 70 ​Gy delivered to PTV70 was defined as GTVPET plus a 0.5 ​cm margin as Plan70. A dosimetric comparison was performed based on normal tissue complication probability (NTCP) for the lung and heart. Results: Clinically acceptable dose escalation failed for 2 of 10 patients in Plan63 due to heart dose constraints. One patient failed heart dose constraint for Plan70. Two patients failed spinal cord constraint for Plan63. Three patients failed lung dose constraints for both Plan63 and Plan70, two of which were even not suitable for Plan50.4 for the same reason.NTCP modeling for lung showed increased risk for Plan63 and Plan70 compared to Plan50.4. The difference between Plan63 and Plan70 was insignificant. NTCP modeling for heart showed an increased risk from 6.38% of Plan50.4 to 8.88% of Plan70 (P ​= ​0.009) or 9.79% of Plan63 (P ​= ​0.007). The risk of heart mortality was significantly higher for Plan63 than Plan70 (P ​= ​0.047). Conclusions: Selective boosting of sub-volumes based on 18F-FDG PET/CT is feasible way with a modest increase in the risk of cardiac and lung toxicities.

Osteoarthritis (OA) is a common and disabling joint disorder that is mainly characterized by cartilage degeneration and narrow joint spaces. The regulatory functions of non-coding RNAs (long non-coding RNAs, microRNAs [miRNAs], and circular RNAs [circRNAs]) in OA progression have attracted considerable attention, and the function of circular RNAs in the context of OA has been an increasingly popular research topic in the last 6 years. Recent studies have reported that various circRNAs can delay or aggravate diverse aspects of the OA process, including extracellular matrix formation, apoptosis, proliferation, inflammation, and autophagy, via circRNA/miRNA/mRNA pathways. Thus, circRNAs and related pathways are potential therapeutic targets for OA. Our review provides comprehensive information about circRNAs, including their biogenesis, functions, and characteristics, and it reveals their critical roles in the pathogenesis of OA via a large regulatory network of sponges. Considering their regulatory functions and characteristics, we hypothesize that circRNAs not only can be transferred through bodily fluids to serve as diagnostic biomarkers, but they can also be released from mesenchymal stem cell-derived exosomes and delivered to OA chondrocytes acting as therapeutic circRNAs. Further investigations of the in-depth molecular mechanisms of action of circRNAs in OA are expected to provide effective and safe OA treatment strategies.

Introduction: Anlotinib has brought about marked progression-free survival and overall survival benefit compared with placebos as third-line or further treatment in advanced NSCLC. Nevertheless, the safety and efficacy of concurrent anlotinib and chemoradiotherapy are still unclear. Methods: Patients with histologically or cytologically confirmed stage III NSCLC suitable for concurrent chemoradiotherapy were enrolled in this study. The enrolled patients were treated with concurrent two cycles of anlotinib and chemoradiotherapy followed by anlotinib consolidation until disease progression or intolerance toxicity. The primary end point was the maximum tolerance dose of anlotinib, whereas the secondary end point was the overall response rate. Results: Seven patients were enrolled in this study. Six patients completed concurrent anlotinib and chemoradiotherapy and then entered the consolidation period. Among the patients, 28.57% (two of seven patients) developed fatal treatment-related adverse events (fatal pneumonitis and fatal hemoptysis). In addition, two other patients developed grade 3 radiation pneumonitis; one was induced by a cold, and the patient received only 18 Gy per nine fractions of radiotherapy. This study was terminated early owing to the high rate of fatal adverse events and radiation pneumonitis. Conclusions: This study presented severe pulmonary toxicity with concurrent anlotinib and chemoradiotherapy. Several previous clinical trials evaluated the safety of concurrent bevacizumab and radiotherapy or chemoradiotherapy; all were terminated owing to severe treatment-related toxicity. Results of these studies suggest that concurrent antiangiogenic and thoracic radiotherapy should be avoided until appropriate safety data are presented, at least for bevacizumab and anlotinib.

Olfactory ensheathing cells (OECs) have shown promising results for patients with neurologic diseases in non-double-blind, placebo control studies. Thirty patients with a unilateral ischemic stroke of more than a year were enrolled in a phase 2, multicenter, randomized, double-blind, and placebo-controlled cell therapy trial with a subsequent 12-month follow-up. The primary therapeutic objective has shown that after 12 months, there were significant differences in National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) assessment scores among the OEC group, Schwann cell group and placebo medium group at one-year follow-up. The second therapeutic objective found that there were significant differences in NIHSS, mRS, and BI assessment scores when comparing the endpoint data with the baseline data in the OEC group. There was neither hypersensitivity reaction nor adverse event. The results of this multicenter, randomized, double-blind, and placebo-controlled study indicate that injecting OECs into the olfactory sub-mucosa have neurorestorative effects, which can improve the quality of life for patients with chronic ischemic strokes without serious side effects.

Communication networks in the tumor microenvironment (TME) play a crucial role in tumor progression. Cancer-associated fibroblasts (CAFs) are among the most abundant stromal cells in the TME. Bidirectional signal transduction between cancer cells and CAFs within the TME is important for cancer development and treatment responsiveness. Extracellular vesicles (EVs) carrying proteins, miRNAs, and other biomolecules are secreted into the extracellular matrix (ECM), which has been demonstrated to be an important communication medium between tumors and CAFs. Tumors regulate the activation of CAFs by secreting EVs. Conversely, CAFs can also affect tumor proliferation, metastasis, and therapeutic resistance through EVs. Here, we will classify EV cargoes and discuss the role of EV-mediated interactions between CAFs and tumors, reviewing current knowledge in combination with our confirmed results.

Objective: To examine the role of total mercury (T-Hg) in placenta as a biomarker of prenatal mercury (Hg) exposure and determine the association between prenatal Hg exposure and risk for neural tube defects (NTDs) in offspring. Methods: Total Hg concentrations in placental tissue were detected in 408 NTD cases and 593 healthy controls enrolled in Shanxi province in northern China. Methylmercury (MeHg) and T-Hg were also detected in the umbilical cord of 147 NTD cases and 140 healthy controls. In addition, MeHg and T-Hg were detected in fetal kidney, liver, and brain tissues of 51 NTD cases. Spearman’s rank correlation (rs) was used to evaluate the correlations between placental T-Hg and T-Hg in umbilical cord and fetal kidney, liver, and brain tissues. The Wilcoxon rank-sum test was used to compare T-Hg amounts between case and control groups. Logistic regression was used to examine the association between placental T-Hg and risk for NTDs. Results: Placental T-Hg was significantly correlated with T-Hg in umbilical cord (rs = 0.479), kidney (rs = 0.718), liver (rs = 0.656), and brain (rs = 0.512) tissues (all p

The mutations of polyglutamine binding protein 1 gene (PQBP1) can lead to the rare inherited X-linked Renpenning syndrome (X-RSY). Here, an induced pluripotent stem cell (iPSC) line WMUi017-A was generated through reprogramming the urine cells of a 5-year-old male X-RSY patient with the hemizygous PQBP1 gene mutation p.P609A (c.1825C>G) using the commercial Sendai virus reprogramming system. The established iPSCs can stably express pluripotent stem cell markers OCT4 and NANOG, and can be induced into three germ layers and maintain a normal karyotype (46, XY) in vitro.

Background: Hand, foot, and mouth disease (HFMD) in adults has rarely been reported in the literature, although its clinical significance is underestimated. This study was performed to systematically elucidate the epidemiological characteristics of adult HFMD. Methods: A total of 266 adult patients with HFMD were recruited. The control group comprised 40 healthy adults. Swabs and serum samples were collected. Enterovirus strains were tested by RT-PCR, and cytokine expression was examined using commercial kits. Socio-demographic data were collected through follow-up telephone calls. Daily meteorological data were obtained from the China Meteorological Data Sharing Service System. Socio-economic data were collected from the statistical bureau. Results: This study identified several unique spatiotemporal patterns in adult HFMD. Having a child recently diagnosed with HFMD was a risk factor for HFMD, whereas keeping pets was a protective factor against HFMD. The results of this study indicate the existence of subclinical carriers or misdiagnosed patients who might be the latent infectious source of HFMD. Further, this study also indicated that adults may act as the main infectious source of trans-regional spread of HFMD. Conclusions: This study revealed the potential hazards of adult HFMD and is a reminder of the vital clinical significance of further research into adult HFMD. Keywords: Adult HFMD, Epidemiological, Subcarrier, Gut microbiome

Background: Adult patients of HFMD might act as potential enterovirus reservoirs. As enterovirus infection will cause acute inflammatory response, identifying the association between the dysregulation of cytokines and the development and prognosis of HFMD in adult patients has vital clinical significance. Methods: 60 patients from 266 laboratory-confirmed adult HFMD cases were included in this study, with 40 healthy adult subjects serving as the controls. Social-demographic data were collected through follow-up phone calls. Serum samples were collected from the participants. Enterovirus genotype was tested by RT-PCR, and the expression of cytokines were examined according to the manufacturer’s instructions. Cases were classified using the cytokine profiles with machine learning algorithm. Results: Adult patients of HFMD presented with dysregulation of cytokines. 15 cytokines of adult patients were significantly elevated and 11 cytokines were decreased compared with those of controls. Correlation analysis showed some cytokines have positive correlation with the clinical characteristics and others have negative correlation. All of the enteroviral genotype presented cytokine dysregulation, and five cytokines were significantly different between genotypes. Using a random forest algorithm, we could classify the cytokine profiles into HFMD class and control class with a very high accuracy. Conclusion: These findings suggested that cytokine expression was correlated with the enteroviral infection, genotype and clinical presentation. The inflammatory profiles could be developed as markers to identify HFMD cases with machine learning algorithm. Keywords: Adult HFMD, Cytokines, Inflammation, Random forest

Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI: 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI: 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI: 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.

Objectives: We aim to investigate association between WNT3A methylation and risk of non-syndromic cleft lip and/or palate (NSCL/P), and examine mediating effect of WNT3A methylation on the association of NSCL/P and lead (Pb) exposure in fetuses. Methods: DNA methylation of WNT3A in umbilical cord blood was determined among 59 NSCL/P cases and 118 non-malformed controls. Mediation analysis was performed to evaluate the potential mediating effect of WNT3A methylation on association between concentrations of Pb in umbilical cord and risk for NSCL/P. Additionally, an animal experiment in which cleft palates were induced by lead acetate was conducted. Results: The overall average methylation level of WNT3A was significant higher in NSCL/P cases as compared to controls. The risk for NSCL/P was increased by 1.90-fold with hypermethylation of WNT3A. Significant correlation was observed between concentrations of Pb in umbilical cord and methylation level of WNT3A. The hypermethylation of WNT3A had a mediating effect by 9.32% of total effect of Pb on NSCL/P risk. Gender-specific association between WNT3A methylation and NSCL/P was observed in male fetuses, and the percentage of the mediating effect increased to 14.28%. Animal experiment of mice showed that maternal oral exposure to lead acetate may result in cleft palate in offspring. Conclusion: Hypermethylation of WNT3A was associated with the risk for NSCL/P and may be partly explain the association between exposure to Pb and risk for NSCL/P. The teratogenic and fetotoxic effects of Pb were found in mice.

Constipation is a disorder that affects people of all ages. Previous study showed Bifidobacterium spp. altered the faecal concentrations of short-chain fatty acids (SCFAs) while relieving constipation. Therefore, we speculated SCFAs might relieve constipation. We evaluated constipation-related indicators, SCFA levels and the faecal microbiota of constipated mice that were fed acylated starches derived from specific SCFAs for 1 month. It confirmed application of acylated starches resolved the issue of SCFAs absorption in small intestine by measuring the concentration of different SCFA in various tissues. Acetylated starch relieved constipation by increasing acetic acid-producing bacteria that were correlated positively with the small intestinal transit rate and water content of faeces, while butylated starch relieved constipation by increasing butyric acid-producing bacteria that were correlated negatively with the time to the first black stool defecation. These results indicated acetic acid and butyric acid play different roles in relieving constipation.

A subset of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients develop Richter transformation (RT), classically resulting in diffuse large B-cell lymphoma (RT-DLBCL); however, a minority of cases result in Hodgkin lymphoma (RT-HL). RT-HL can be of type 1 or 2. RT-HL1 consists of Hodgkin-Reed Sternberg (HRS) cells in a background of CLL, and RT-HL2 has HRS cells in the typical inflammatory background of classical HL (CHL). Here we describe a rare case of CLL with an increased number of HRS-like cells which evolved to Epstein–Barr virus (EBV)-positive DLBCL over 2 years. The patient was a 48-year-old man who initially presented with right inguinal lymphadenopathy and was found to have both CLL/SLL and HSV lymphadenitis, which was then treated with valacyclovir and acyclovir prophylaxis. Approximately 1 year later, he developed diffuse lymphadenopathy with CLL and scattered EBV-positive HRS-like cells, consistent with RT-HL1, for which he received rituximab. After 3 months, he again developed diffuse lymphadenopathy with worsening symptoms. The patient was diagnosed with EBV-positive DLBCL by lymph node biopsy and responded well to 6 cycles of R-CHOP. This is the first case of CLL with RT-HL1 predating RT-DLBCL. While RT-HL1 and RT-DLBCL have been described previously, the potential for an association between these entities is cryptic. As more cases are reported, this relationship can be studied in greater detail.

This study examined the associations between concentrations of cobalt (Co), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) in placental tissue and risks for NTDs with a case-control design consisting of 408 fetuses or newborns with neural tube defects (NTDs) and 593 non-malformed fetuses or newborns. The concentrations of Zn and Fe were determined by inductively coupled plasma-emission spectrometer and the other four elements by inductively coupled plasma-mass spectrometer. Element concentrations were presented in ng/g or µg/g dry weight of placental tissue. The associations between the levels of each of the six ETEs and risk for NTDs were evaluated using multivariable logistic regression, and the associations between overall levels of all six ETEs and risk for NTDs were examined using Bayesian kernel machine regression (BKMR). Concentrations above the median concentration of all participants for an individual element were associated with increased risk for NTDs: Mn, 3.17-fold (95% CI 2.35–4.28); Mo, 3.73-fold (95% CI 2.74–5.07); Se, 3.28-fold (95% CI 2.44–4.42); and Zn, 2.85-fold (95% CI 2.13–3.83), and a decreased risk for Co [OR, 0.18 (95% CI 0.14–0.25)]. The risk for NTDs increased with the increase in the concentrations of Mn, Mo, Se, and Zn, but decreased for Co, in the second, third, and fourth quartiles, respectively, compared to their lowest quartile (all Pstrend

Rare earth elements (REEs) are ubiquitous in the environment. Animal experiments have shown that many REEs have adverse impacts on the health of fetuses. However, data from humans are scarce. In this study, we examined the associations between concentrations of 10 REEs in maternal serum and the risk for fetal neural tube defects (NTDs). The study included 200 pregnant women with pregnancies affected by NTDs and 400 pregnant women with healthy fetuses/infants. Fifteen REEs in maternal serum were assessed; 10 of them were detectable in over 60% of samples and were included in statistical analyses, including lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), terbium (Tb), dysprosium (Dy), lutetium (Lu), and yttrium (Y). When the elements were considered individually with the use of Logistic regression model, the risk for NTDs increased by 2.78-fold (1.25–6.17) and 4.31-fold (1.93–9.62) for La, and 1.52-fold (0.70–3.31) and 4.73-fold (2.08–10.76) for Ce, in the second and third tertiles, respectively, compared to the lowest concentration tertile. When Bayesian kernel machine regression was used to examine the joint effect of exposure to all 10 REEs, the risk for NTDs increased with overall levels of these REEs and the association between La and NTD risk remained when other nine elements were taken into consideration simultaneously. Taken together, this study shows that the risk for NTDs increases with La concentrations when single REEs are considered and with concentrations of all 10 REEs when these REEs are considered as a co-exposure mixture. Keywords: Rare earth element, Neural tube defect, Serum, Pregnancy, Bayesian kernel machine regression

Non-alcoholic fatty liver disease (NAFLD) is an emerging global disease with increasing prevalence. However, the mechanism of NAFLD development is not fully understood. To elucidate the cell-specific role of nuclear factor erythroid-derived 2-like 2 (NRF2) in the pathogenesis of NAFLD, we utilized hepatocyte- and macrophage-specific Nrf2-knockout [Nrf2(L)-KO and Nrf2(Mϕ)-KO] mice to examine the progress of NAFLD induced by high-fat diet (HFD). Compared to Nrf2-LoxP littermates, Nrf2(L)-KO mice showed less liver enlargement, milder inflammation and less hepatic steatosis after HFD feeding. In contrast, Nrf2(Mϕ)-KO mice displayed no significant difference in HFD-induced hepatic steatosis from Nrf2-LoxP control mice. Mechanistic investigations revealed that Nrf2 deficiency in hepatocytes dampens the expression of peroxisome proliferator-activated receptor γ (PPARγ) and its downstream lipogenic genes in the liver and/or primary hepatocytes induced by HFD and palmitate exposure, respectively. While PPARγ agonists augmented PPARγ expression and its transcriptional activity in primary hepatocytes in a NRF2-dependent manner, forced overexpression of PPARγ1 or γ2 distinctively reversed the decreased expression of their downstream genes fatty acid binding protein 4, lipoprotein lipase and/or fatty acid synthase caused by Nrf2 deficiency. We conclude that NRF2-dependent expression of PPARγ in hepatocytes is a critical initiating process in the development of NAFLD, suggesting that inhibition of NRF2 specifically in hepatocytes may be a valuable approach to prevent the disease. Keywords: Nrf2, NALFD, High-fat diet, Hepatocyte, PPARγ

Lightweight and high-strength hybrids are of great importance for reducing material and energy consumptions. Glass fiber-reinforced polyphenylene sulfide (PPS) and aluminum (Al) alloy 6061 were joined via flexible injection molding technology. With pretreatments of anodizing and the coupling agent, the maximal lap shear strength between the polymer and metal were noticeably enhanced to 7.7 MPa, which was almost eight fold compared with the untreated case. The scanning electron microscope (SEM) and X-ray photoelectron spectrometer (XPS) investigations proved that the micro cracks with widths of nanometer scale and chemical Al-O-Si bonds were formed on the metal substrate, which contribute significantly to the interface bonding strength. According to Fourier transform infrared (FTIR) investigations, the existing C-N bonds in the coupling-agent layer on the metal surface also have a crucial effect on the bonding strength of the two dissimilar materials. The present novel methodology is much more convenient than other current commercial available technologies, and provides a promising way for the production of polymer-metal hybrids. Keywords: Anodizing, Injection molding, Microstructure, Polymer-metal hybrid

The aim of this study was to evaluate the effects of different kinds of oligosaccharides on cecal microbiota. These oligosaccharides were a fructo-oligosaccharide (FOS) formulation consisting of 95% FOS (FOS95), a galacto-oligosaccharide (GOS) formulation consisting of 90% GOS (GOS90), and an isomalto-oligosaccharide (IMO) formulation consisting of 90% IMO (IMO90), at dosages of 0.8, 4, and 8 g/d/kg bw. FOS95, IMO90, and GOS90 were each gavaged to BALB/c mice for 14 days. Sequencing of 16S rDNA amplicons showed that the abundance of Actinobacteria and TM7 dramatically decreased in constipation group. Feeding constipated mice with FOS95, IMO90, and GOS90 resulted in decreased ratio of Firmicutes to Bacteroidetes, and increased abundances of Bifidobacterium, Bacteroides, Rikenella, Lactobacillus, and Clostridium and decreased abundances of Oscillospira, Coprococcus, and Dorea at the genus level. Overall, our results demonstrate that FOS95, IMO90, and GOS90 modulate the cecal microbiome in constipated mice.

In an environment marked with phenomena such as globalization and creation, open innovation is critical for universities to cooperate with external resources and meet the requirements of the era. To investigate open innovation ecosystem of higher education, we use secondary data and interviews to analysis interactive model of Zizhu International Education Park from both internal and external perspectives. The analysis result suggests that the open innovation ecosystem could have positive effects on the development of higher education. It can contribute to deepening the integration of production, teaching, and research; improve the efficiency of scientific research transformation; and use this part of the income to supplement school funding. While the university–industry collaborative relationship could also be a limiting factor for it.

The objective of this study is to investigate the feasibility of using chitosan–sodium alginate (CS–SA) based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables. Using trimetazidine hydrochloride (TH) as a water-soluble model drug, influence of dissolution medium, the amount of CS–SA, the CS:SA ratio, the type of SA, the type and amount of diluents, on in vitro drug release from CS–SA based matrix tablets were studied. Drug release kinetics and release mechanisms were elucidated. In vitro release experiments were conducted in simulated gastric fluid (SGF) followed by simulated intestinal fluid (SIF). Drug release rate decreased with the increase of CS–SA amount. CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found. On the other hand, a large amount of water-soluble diluents could modify drug release profiles. It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism. In conclusion, this study demonstrated that it is possible to design extended-release tablets of water-soluble drugs using CS–SA as the matrix by optimizing formulation components, and provide better understanding about drug release from CS–SA matrix tablets.

Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with human herpesvirus 8 (HHV8), which usually presents as a lymphomatous body cavity effusion. Rare cases of PEL are extracavitary and manifest as a solid tumor mass. Here we report an unusual case of extracavitary PEL (EPEL) involving lymph nodes with no evidence of a body cavity effusion. The neoplasm was comprised of large pleomorphic cells with prominent nucleoli and frequent mitotic figures that expressed HHV8, EBV, CD38 and CD30, but lacked all lineage-specific markers. The patient was found to be HIV positive after the diagnosis of EPEL. Antiretroviral therapy initially reduces tumor size, but the patient expired three months later due to multiple complications. PEL and EPEL are differing manifestations of a rare disease entity as defined by the World Health Organization 2008 classification. It is unknown why a small subset of these cases forms extracavitary masses with or without malignant effusions. Comparison with mouse xenograft models may provide unique insights into the pathogenesis of this disease for possible future studies.