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Abstract Sepsis-induced cardiomyopathy (SIC) is described as a reversible myocardial depression that occurs in patients with septic shock. Increasing evidence shows that microRNA-194-5p (miR-194-5p) participates in the regulation of oxidative stress, mitochondrial dysfunction, and apoptosis and its expression is associated with the occurrence and progression of cardiovascular disease; however, the effects of miR-194-5p in SIC are still unclear. This study explores whether miR-194-5p could modulate SIC by affecting oxidative stress, mitochondrial function, and apoptosis. Experimental septic mice were induced by intraperitoneal injection of lipopolysaccharide (LPS) in C57BL/6J mice. The biological role of miR-194-5p in SIC in vivo was investigated using cardiac echocardiography, ELISA, western blot, qRT-PCR, transmission electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, bioinformatics analysis, and dual-luciferase reporter gene assay. Our major finding is that miR-194-5p antagomir mitigates sepsis-induced cardiac dysfunction, inflammation, oxidative stress, apoptosis and mitochondrial dysfunction in the hearts of septic mice, while miR-194-5p agomir triggers the opposite effects. Furthermore, dual-specificity phosphatase 9 (DUSP9) is a direct target of miR-194-5p and the cardioprotective effects of miR-194-5p antagomir on cardiac dysfunction, inflammation, apoptosis, mitochondrial dysfunction and oxidative stress are abolished through inhibiting DUSP9. Therefore, miR-194-5p inhibition could mitigate SIC via DUSP9 in vivo and the novel miR-194-5p/DUSP9 axis might be the potential treatment targets for SIC patients.

Abstract The multi-criteria decision-making (MCDM) field has long sought tools capable of adeptly capturing the intricacies of human decision-making amidst uncertainty. Hesitant fuzzy sets (HFS) have become a cornerstone in the MCDM field due to their ability to capture the intricacies of human decision-making under uncertainty. Nonetheless, we identified a significant gap in traditional HFS formulations, which often fail to fully harness the nuanced and implicit preferences of decision-makers (DMs). This shortcoming can lead to suboptimal decision outcomes in complex and uncertain environments. We introduce the normal wiggly hesitant fuzzy set (NWHFS), a novel construct that encapsulates both explicit and implicit preferences within a more representative framework. This study pioneers the development of new correlation coefficients for NWHFSs, offering a robust quantitative measure to elucidate the intricate relationships between variables. Our findings demonstrate that NWHFSs significantly enhance the MCDM process, providing a nuanced perspective that traditional HFS models cannot match. The proposed correlation coefficients not only reveal the concealed preferences of DMs but also broaden the decision-making spectrum, offering a more profound understanding of the relationships between alternatives and criteria. We illustrate the superiority of our approach through comparative analysis with existing methods, highlighting its ability to discern subtleties that other models overlook. Moreover, we integrate NWHFSs into clustering analysis, showcasing their potential to classify data sources with shared attributes effectively. This integration is particularly noteworthy for its ability to navigate complex datasets, offering a new dimension in data mining and resource retrieval. In essence, our study redefines the MCDM paradigm by introducing NWHFSs and their correlation coefficients, setting a new standard for decision-making accuracy and insight. The implications of our work extend beyond theory, offering practical solutions to real-world decision-making challenges.

Abstract This study delves into the micro-occurrence states and enrichment mechanisms of residual oil, pivotal for advancing the production from tight sandstone reservoirs, particularly from the Chang 8 Member of the Upper Triassic Yanchang Formation, Ordos Basin. Through an analysis of 23 core samples, employing high-pressure mercury injection, field emission scanning electron microscopy, thin section, and X-ray diffraction techniques, distinct reservoir types were categorized. The utilization of environmental scanning electron microscope, multi-solvent continuous extraction, and an oil components separation system facilitated an intricate analysis of residual oil micro-occurrence states and their subsequent effects on porosity and permeability reduction across varying reservoir types. The findings accentuate the integral role of reservoir type in determining residual oil distribution within tight sandstone reservoirs. Favorable pore throat sorting and connectivity in specified reservoir types are identified as conducive to residual oil enrichment with a higher concentration of light components. In contrast, elevated carbonatite and clay content in other reservoir types leads to adsorption of heavy components, disrupting pore throat connectivity, and impeding crude oil filling. The varied interactions between oil and rock, oil–oil, and pore throat sealing significantly impact the distribution of oil components of residual oil, culminating in a notable reduction of porosity and permeability by 2.63% and 0.197 mD, with corresponding reduction rates of 27.19% and 46.69%, respectively. The insights derived from this study furnish a theoretical foundation for augmenting tight oil recovery and comprehending the enrichment mechanism of residual oil driven by the heterogeneity of tight sandstone reservoirs.

Adenoviral infections, particularly in children, remain a significant public health issue with no approved targeted treatments. Artemisinin and its derivatives, well-known for their use in malaria treatment, have shown antiviral activities in recent studies. However, their efficacy against human adenovirus (HAdV) remains unexplored. This study aimed to assess the activity of artemisinin and its derivatives against HAdV infection in vitro using cell lines and primary cells. Our data revealed that artemisinin exhibited dose-dependent anti-HAdV activity with no apparent cytotoxicity over a wide concentration range. Mechanistically, artemisinin did not affect viral attachment or entry into target cells, nor the viral genome entry into cell nucleus. Instead, it inhibited HAdV through suppression of viral DNA replication. Comparative analysis with its derivatives, artesunate and artemisone, showed distinct cytotoxicity and anti-adenoviral profiles, with artemisone showing superior efficacy and lower toxicity. Further validation using a primary airway epithelial cell model confirmed the anti-adenoviral activity of both artemisinin and artemisone against different virus strains. Together, our findings suggest that artemisinin and its derivatives may be promising candidates for anti-HAdV treatment.

Abstract Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.

Despite major advances in non-small-cell lung cancer (NSCLC) treatment, the five-year survival rates for patients with non-oncogene-driven tumors remain low, necessitating combinatory approaches to improve outcomes. Our prior high-throughput RNAi screening identified Aurora kinase A (AURKA) as a potential key player in cisplatin resistance. In this study, we investigated AURKA’s role in platinum and radiation sensitivity in multiple NSCLC cell lines and xenograft mouse models, as well as its effect on immune checkpoints, including PD-L1, B7x, B7-H3, and HHLA2. Of 94 NSCLC patient tumor specimens, 91.5% tested positive for AURKA expression, with 34% showing moderate-to-high levels. AURKA expression was upregulated following cisplatin treatment in NSCLC cell lines PC9 and A549. Both AURKA inhibition by alisertib and inducible AURKA knockdown potentiated the cytotoxic effects of cisplatin and radiation, leading to tumor regression in doxycycline-inducible xenograft mice. Co-treated cells exhibited increased DNA double-strand breaks, apoptosis, and senescence. Additionally, AURKA inhibition alone by alisertib increased PD-L1 and B7-H3 expression. In conclusion, our study demonstrates that AURKA inhibition enhances the efficacy of platinum-based chemotherapy in NSCLC cells and modulates the expression of multiple immune checkpoints. Therefore, combinatory regimens with AURKA inhibitors should be strategically designed and further studied within the evolving landscape of chemo-immunotherapy.

Introduction: Jiangtang Sanhao Formula (JTSHF), composed of Panax ginseng, Atractylodes macrocephala, Coptis chinensis, Salvia miltiorrhiza and several other herbs, is a traditional Chinese medicine formula commonly used to treat type 2 diabetes. This compound shows significant clinical efficacy in the treatment of diabetic, however, its target and pharmacological mechanism are still unclear. The present study explored the therapeutic effect of JTSHF on diabetic mice and conducted RNA sequencing to investigate the potential mechanism. Methods: The T2DM mice model was established using a high-fat diet combined with an intraperitoneal injection of low-dose STZ. Fasting blood glucose (FBG), serum insulin, glucose tolerance, and blood lipids in mice from different groups were examined. Then the effects of JTSHF on oxidative stress and liver histopathology in diabetic mice were observed. Next, transcriptome analysis was performed to identify differentially expressed genes (DEG), which were validated using real-time quantitative PCR (RT-qPCR). By using pathway enrichment analysis, we identified several key pathways which are essential in the JTSHF effect on T2DM. Finally, we constructed ceRNA network to illustrate the regulatory effect of JTSHF on transcriptional profile in diabetic liver. Results: JTSHF reduced FBG level and blood lipid contents, ameliorated glucose tolerance and improved insulin sensitivity in diabetic mice. It also showed protective effects on fatty livers induced by high-fat diet and diabetes. For the first time, we revealed that JTSHF exerts anti-T2DM role in the liver of diabetic mice, which is associated with multiple molecular targets and signaling pathways. Enrichment analysis and treatment-based mRNA-ncRNA-miRNA ceRNA networks revealed that JTSHF might exerts therapeutic effect by modulating lipid metabolism. Discussion: Our research found that JTSHF exerts anti-T2DM effect by affecting multiple pathways. Among these, lipid metabolism and oxidative stress might be involved. The present study provided novel insights for the mechanism of JTSHF, and the differentially expressed genes identified can be potential therapeutic targets in the treatment of T2DM in future.

Abstract Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE−/−: Sirt6−/− and ApoE−/−: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE−/−: Sirt6−/− mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6’s function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.

Abstract Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients.

Carbon neutrality target triggers the acceleration of China's rural energy revolution and energy transition. It is an irreversible trend that coal will phase out Rural Household Energy Mix (RHEM) in the long run. Problem is how coal will phase down and phase out in an orderly, effective, fair and high-quality way. National rural household energy consumption of all types is reviewed and related carbon emission accounted to manifest the evolvement of coal’s role, status and impacts in China’s RHEM since 1949. Household-level survey carried out in rural Beijing has discovered problems and challenges in the phasing out coal due to policy enforcement. Exergy is further assessed and predicted. The future role and contribution of coal among RHEM is identified for outlining coal’s phase out path by considering the resilience, economy and differentiated bottlenecks of carbon-neutral RHEM from the three-dimensional perspective of exergy, base energy context and comparative comprehensive cost-benefit calculation of energy substitution. The conclusions are as follows: ① Per capita energy consumption and exergy demand will continue to increase in coming years, and the per capita electricity consumption peak in a full electrification mode of RHEM is conservatively estimated to be about 5 000 kW·h. ② In the long run, rural household energy electrification has the characters of carbon neutrality, renewability and marketization. The coal revolution in RHEM, pursuing an improved cleaner and affordable energy pattern, consists of sustainable energy replacing coal and coal replacing biomass fuels. Before rural green energy market fully developed, coal is still the “ballast” for rural energy security. ③ In accordance with regional differences, it is wise to resort to five sub-path combinations belonging to three coal phaseout paths, that is, coal neutrality (improved stove technology and let the coal be), coal substitution (including coal replacement of primary biomass; clean coal upgrading) and coal substituted (inclusive of voluntary and mandatory phaseout of coal). It is anticipated that rural residents will enjoy a modern carbon-neutral energy system with resilience and fairness in future China.

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality. In addition, LYC treatment inhibited ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and promoting osteogenesis during bone remodeling. At the molecular level, LYC improved bone quality via an increase in the expressions of FoxO1 and Runx2 and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regulation of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for osteoporosis management.

Renal ischemia-reperfusion (I/R) injury leads to irreversible brain damage with serious consequences. Activation of oxidative stress and release of inflammatory mediators are considered potential pathological mechanisms. Butylphthalide (NBP) has anti-inflammatory and antioxidant effects on I/R injuries. However, it is unclear whether NBP can effectively mitigate renal I/R secondary to brain injury as well as its mechanism, which are the aims of this study. Both renal I/R injury rats and oxygen and glucose deprivation cell models were established and pre-intervened NBP. The Morris water maze assay was used to detect behavior. Hippocampal histopathology and function were examined after renal I/R. Apoptosis and tube-forming capacity of brain microvascular endothelial cells (BMVECs) were tested. Immunohistochemistry and Western blot were used to measure protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway and NOD-like receptor C2 (NOD2)/Mitogen-activated protein kinases (MAPK)/Nuclear factor kappa-B (NF-κB) pathway. NBP treatment attenuated renal I/R-induced brain tissue damage and learning and memory dysfunction. NBP treatment inhibited apoptosis and promoted blood-brain barrier restoration and microangiogenesis. Also, it decreased oxidative stress levels and pro-inflammatory factor expression in renal I/R rats. Furthermore, NBP enhanced BMVECs’ viability and tube-forming capacity while inhibiting apoptosis and oxidative stress. Notably, the alleviating effects of NBP were attributed to Nrf2/HO-1 pathway activation and NOD2/MAPK/NF-κB inhibition. This study demonstrates that NBP maintains BBB function by activating the Nrf2/HO-1 pathway and inhibiting the NOD2/MAPK/NF-κB pathway to suppress inflammation and oxidative stress, thereby alleviating renal I/R-induced brain injury.

Consumer acceptance of Keitt mangoes (Mangifera indica L.) is significantly affected by their slow postharvest ripening. This work used gaseous chlorine dioxide (ClO2(g)) to prepare the ready-to-eat Keitt mango and explored the potential mechanisms for the mango ripening. Harvested mangoes were treated with 20 mg·L−1 of ClO2(g) or ethephon for 3 h (25 °C) and left in a climatic chamber with a temperature of 25 ± 1 °C and a relative humidity of 85 ± 5% for 4 d. The results showed that ClO2(g) treatment significantly promoted the orange coloration of mango flesh compared to the untreated control group. Moreover, ClO2(g) treatment significantly elevated the total soluble solids, total soluble sugar, and total carotenoids content of mangoes, whereas the firmness and titratable acidity were reduced. ClO2(g)-treated mangoes reached the edible window on day 2, as did mangoes treated with ethephon at the same concentration, except that the sweetness was prominent. The residual ClO2 level of the mangoes was 2(g) significantly advanced the onset of ethylene peaks by 0.5 days and increased its production between days 0.5 and 2 compared to the control group. Consistently, the genes involved in ethylene biosynthesis including miACS6, miACO1, and miACO were upregulated. In sum, ClO2(g) can be a potential technique to reduce the time for harvested mango to reach the edible window, and it functions in modulating postharvest ripening by inducing ethylene biosynthesis.

The massive amount and multi-sourced, multi-structured data in the upstream petroleum industry impose great challenge on data integration and smart application. Knowledge graph, as an emerging technology, can potentially provide a way to tackle the challenges associated with oil and gas big data. This paper proposes an engineering-based method that can improve upon traditional natural language processing to construct the domain knowledge graph based on a petroleum exploration and development ontology. The exploration and development knowledge graph is constructed by assembling Sinopec’s multi-sourced heterogeneous database, and millions of nodes. The two applications based on the constructed knowledge graph are developed and validated for effectiveness and advantages in providing better knowledge services for the oil and gas industry.

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma are common subtypes of thyroid cancer, while hyalinizing trabecular tumor (HHT) of the thyroid is a rare peculiar type of follicular cell neoplasm. Although all three tumor types originate from thyroid follicular cells, the frequency of their co-presence in the same thyroid gland is unknown. Herein, we describe an extremely rare case with three types of concurrent thyroid neoplasms in one patient. This patient was a 60-year-old female who presented with large symptomatic multinodular goiter clinically. Fine needle aspiration of the right thyroid nodule showed atypia of undetermined significance. She then received total thyroidectomy. Microscopically, there were 3 types of tumors identified: multifocal (x4) PTC (largest focus 1.5 cm) with focal tall cell features, encapsulated angioinvasive oncocytic carcinoma (8.2 cm), and a small HHT (0.6 cm). The HHT was encapsulated, containing spindled to polygonal cells with oval to elongated nuclei arranged in a trabecular growth pattern. The PTC and oncocytic carcinoma were diagnosed by morphology only. The diagnosis of HHT was confirmed by immunohistochemistry showing the tumor cells to be positive for pan-cytokeratin, thyroglobulin, TTF-1, and PAX8, while negative for synaptophysin, chromogranin, and calcitonin. Next generation sequencing demonstrated different molecular alterations: BRAF V600E mutation in PTC; NRAS mutation in oncocytic carcinoma, and HRAS mutation in HHT. This is the first case report of triple thyroid neoplasms occurring synchronously in one patient. The unique genetic alteration of each individual tumor suggests different pathogenetic mechanisms.

Abstract Background This study aimed to determine the effect of type 2 diabetes mellitus (T2DM) on overall survival (OS) of patients with stage IIIB–IV non‐small cell lung cancer (NSCLC). Methods We retrospectively analyzed patients with stage IIIB–IV NSCLC from January 2015 to December 2018 in the Department of Oncology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Kaplan–Meier plots, log‐rank tests, and Cox proportional hazards regression models were used to describe the effect of T2DM on the OS of patients with stage IIIB–IV NSCLC. Results This study collected data on 76 patients with NSCLC and T2DM (group A) and 214 NSCLC patients without T2DM (group B). After propensity score matching (PSM) analysis, 74 patients were included in each group. The mean OS of all patients was 17 months (range, 11–31 months). The mean OS of group A was 15 months (range, 8–25 months) and the mean OS of group B was 20 months (range, 14–39 months). The mean OS of group B was longer than group A, and the difference was statistically significant. Univariate analysis of the clinical data showed that T2DM and complications were significantly correlated with the prognosis of patients with stage IIIB‐IV NSCLC (p = 0.003 and p = 0.034). Multivariate Cox model analysis showed that T2DM and complications were independent prognostic factors for patients with stage IIIB–IV NSCLC (p = 0.002 and p = 0.024, respectively). Conclusion Stage IIIB–IV NSCLC patients without T2DM have an increased OS compared to patients with stage IIIB–IV NSCLE and T2DM.

In order to comprehensively develop the biological resources of sea buckthorn, five hybrid sea buckthorn berries including Zaciyou 1, Zaciyou 2, Zaciyou 10, Zaciyou 12, and Zaciyou 54 were used as test materials to compare and analyze. The vitamin C, vitamin E, total flavonoids, anthocyanins, titratable acids, β-carotene, soluble sugar, glucose, fructose, sucrose content and superoxide dismutase (SOD) enzyme activity were determined and their correlations were analyzed. The results showed that the content of each nutrient component was related to the variety and maturity of sea buckthorn. When the five hybrid sea buckthorn varieties participated in the test were fully mature, the content of vitamin C and vitamin E could reach 318.28~531.78 and 7.60~13.14 mg/100 g, respectively, and the content of soluble sugar and titratable acid could reach 32.61~84.36 mg/g, 0.97%~1.95%, the contents of β-carotene and total flavonoids could reach 22.31~47.82 µg/g and 1.41~3.53 mg/g, respectively. Among the five hybrid sea buckthorn varieties tested, Zaciyou 10 sea buckthorn had higher nutritional content. Correlation analysis showed that the contents of VE, β-carotene, anthocyanin, glucose and total flavonoids in the five hybrid sea buckthorn berries were very significant correlation with each other (P

Acupuncture has gained growing attention in the management of osteoporosis (OP). However, a comprehensive review has not yet been conducted on the efficacy and challenges of acupuncture in preliminary research and clinical trials. Therefore, an extensive literature search was conducted using electronic databases, including PubMed (www.ncbi.nlm.nih.gov/pubmed), CNKI (www.cnki.net), and Web of Science, for studies published from the beginning of 2000 to the end of May 2022. Combinations of synonyms for OP, acupuncture, traditional Chinese medicine, clinical trial, preclinical study, and animal experiments were searched. A total of 290 papers were consulted, including 115 reviews, 109 clinical observations, and 66 preclinical studies. There is accumulating evidence to support the beneficial role of acupuncture in preserving bone quality and relieving clinical symptoms based on clinical and preclinical investigations. The top ten most commonly used acupoints are BL23, ST36, BL20, BL11, CV4, GV4, SP 6, KI3, BL18, and GB39. The underlying mechanisms behind the benefits of acupuncture may be linked with the regulation of the hypothalamic-pituitary-gonadal (adrenal) axis and activation of the Wnt/β-catenin and OPG/RANKL/RANK signaling pathways. In summary, strong evidence may still come from prospective and well-designed clinical trials to shed light on the potential role of acupuncture in preserving bone loss. Future investigations are needed to explore the potential underlying mechanisms, long-term clinical efficacy, and compliance of acupuncture in OP management.

Abstract Dyslipidemia is an independent risk factor of cardiovascular diseases (CVDs), which lead to the high mortality, disability, and medical expenses in the worldwide. Based on the previous researches, the improvement of dyslipidemia could efficiently prevent the occurrence and progress of cardiovascular diseases. Medicinal and edible plants (MEPs) are the characteristics of Chinese medicine, and could be employed for the disease treatment and health care mostly due to their homology of medicine and food. Compared to the lipid-lowering drugs with many adverse effects, such as rhabdomyolysis and impaired liver function, MEPs exhibit the great potential in the treatment of dyslipidemia with high efficiency, good tolerance and commercial value. In this review, we would like to introduce 20 kinds of MEPs with lipid-lowering effect in the following aspects, including the source, function, active component, target and underlying mechanism, which may provide inspiration for the development of new prescription, functional food and complementary therapy for dyslipidemia.

Objective: We aimed to observe the effects of loganin (Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase (AMPK) signaling in obese mice. Methods: A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research (ICR) mice. Body weight was measured weekly and fasting blood glucose (FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol (TC), triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), and free fatty acids (FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing. Results: Log significantly decreased the body weight and the FBG in obese mice (P

Abstract Background Talaromyces marneffei is an opportunistic pathogen that infects immunodeficient and immunocompromised patients. We presented a pediatric patient with a diagnosis of T. marneffei infection who was followed up in the Guangzhou Women and Children’s Medical Centre. Case presentation The child was a 5-year-old girl with persistent cough and gasping over 2 months who was confirmed with T. marneffei infection by bronchoalveolar lavage fluid culture and high-throughput sequencing technology. Human immunodeficiency virus (HIV) was negative according to a serum-specific antibody test. She was treated with amphotericin B and itraconazole as antifungal agents, with good clinical response. At follow-up, high-resolution computed tomography showed a mosaic sign in the whole lung field with a diagnosis of post-infectious bronchiolitis obliterans (PIBO) as the sequela. She has a mutated COPA gene with uncertain pathogenic potential on whole-exome sequencing. Conclusions Clinicians should consider PIBO as a possible sequela in an HIV-negative paediatric patient with T. marneffei infection.

There is great potential for tight oil as an alternative to conventional fossil fuels throughout the world. Adsorption, mineralogy, and pore structure of tight sandstone are very important factors for the efficient development of adsorbed tight oil from tight sandstone oil reservoirs. In this study, the occurrence morphology of tight oil adsorbed to varying pore structures was examined, as well as the relationship between adsorption content and occurrence morphology. X-ray energy dispersive spectra, environmental scanning electron microscope observations, and thin fluorescence sections were used to describe the occurrence morphology of adsorbed tight oil in tight sandstone reservoirs. It was found that adsorbed tight oil can be classified into five types: emulsion, cluster, throat, thin-film, and isolation, with average contents of 34.9%, 14.5%, 3.1%, 42.7%, and 4.7%, respectively. In addition, a Soxhlet extraction was developed with four pore structures to describe the geological effects of adsorbed tight oil in reservoirs. The adsorption content of tight oil ranges from 4.015 mg/g to 16.987 mg/g, with an average of 10.115 mg/g. The order of adsorption content for different occurrence morphologies is as follows: emulsion form > throat form > cluster form > isolation form > thin-film form. It is the size and connectivity of the porous throat that determines the desorption efficiency of tight oil. An important outcome of this study can be the introduction of rational development plans and the improvement of oil recovery efficiency for tight oil reservoirs.

The detection algorithm of the apple-picking robot contains a complex network structure and huge parameter volume, which seriously limits the inference speed. To enable automatic apple picking in complex unstructured environments based on embedded platforms, we propose a lightweight YOLOv5-CS model for apple detection based on YOLOv5n. Firstly, we introduced the lightweight C3-light module to replace C3 to enhance the extraction of spatial features and boots the running speed. Then, we incorporated SimAM, a parameter-free attention module, into the neck layer to improve the model’s accuracy. The results showed that the size and inference speed of YOLOv5-CS were 6.25 MB and 0.014 s, which were 45 and 1.2 times that of the YOLOv5n model, respectively. The number of floating-point operations (FLOPs) were reduced by 15.56%, and the average precision (AP) reached 99.1%. Finally, we conducted extensive experiments, and the results showed that the YOLOv5-CS outperformed mainstream networks in terms of AP, speed, and model size. Thus, our real-time YOLOv5-CS model detects apples in complex orchard environments efficiently and provides technical support for visual recognition systems for intelligent apple-picking devices.

Deqin County is one of the areas suffering the most serious geological disasters in Yunnan Province. Based on the development characteristics of the debris flow in the Zhixi River, this study identifies five disaster-generating modes for the debris flow in the Zhixi River: Collapse - clastic flow, rock landslide-clastic flow, soil-rock mixture landslide-clastic flow, loose accumulation layer -bedrock contact surface landslide-clastic flow and landslide in loose accumulation layer-clastic flow. The FLO-2D model is used to simulate the debris flow movement in the Zhixi River under the rainstorm cycle of 10, 20, 50 and 100 years, and the maximum flow velocity, the maximum accumulation depth, the accumulation distance and the volume scale in different rainfall return periods are quantitatively analyzed. The results show that the debris flow is characterized by high acceleration, fast velocity, strong destructive force, and long circulation area when it erupts. When the debris flow occurs once in 100 years, its maximum velocity reaches 3.07 m/s, the maximum mud depth is 2.27 m , the volume of debris flow washed out is 84419 m3, and the disaster area reaches 91600 m2. The results provide quantitative data reference for the prevention and control of debris flow disasters in Zhixi River, and also provides an important basis for the design of disaster prevention and mitigation projects in Deqin County.

Abstract Background Some children hospitalized for severe pertussis need intensive care; moreover, some children die because of deterioration alone or in combination with other complications. The purpose of this study was to identify the mortality risk factors among hospitalized children with severe pertussis. Methods This study evaluated the medical records of 144 hospitalized children with severe pertussis at the Guangzhou Women and Children’s Medical Centre between January 2016 and December 2019. Results The median age of patients was 2 months (IQR 1–4 months), with 90.3% of the patients aged 70.0 × 109/L (odds ratio [OR], 230.66; 95% confidence interval [CI], 5.16–10,319.09 P = 0.005) and pulmonary hypertension (PH) (OR 323.29; 95% CI 16.01–6529.42; P 70.0 × 109/L and PH were the prognostic independent variables associated with death.

ABSTRACT Pneumonia is the leading cause of death in children; the pathogens are often difficult to diagnose. In this study, the performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from 112 children with confirmed pneumonia has been evaluated. mNGS performed a significantly higher positive detection rate (91.07%, 95% confidence interval [CI] 83.80% to 95.40%) and coincidence rate against the final diagnosis (72.32%, 95% CI 62.93% to 80.15%) than that of conventional methods (70.54%, 95% CI 61.06% to 78.58% and 56.25%, 95% CI 46.57% to 65.50%, respectively) (P < 0.01 and P < 0.05, respectively). Bacteria, viruses, and their mixed infections were common in children with pneumonia. Streptococcus pneumoniae was the most common bacterial pathogen in children with pneumonia, while Haemophilus parainfluenzae and Haemophilus influenzae seemed more likely to cause nonsevere pneumonia in children. In contrast, human cytomegalovirus (CMV) infection and the simultaneous bacterial infections could cause severe pneumonia, especially in children with underlying diseases. After adjustments of antibiotics based on mNGS and conventional methods, the conditions improved in 109 (97.32%) children. mNGS of BALF samples has shown great advantages in diagnosing the pathogenic etiology of pneumonia in children, especially when considering the limited volumes of BALF and the previous use of empirical antibiotics, contributing to the timely adjustment of antibiotic treatments, which can potentially improve the prognosis and decrease the mortality. IMPORTANCE Our study indicates high efficiency of mNGS using BALF for the detection of causative pathogens that cause pneumonia in children. mNGS can be a potential diagnostic tool to supplement conventional methods for children’s pneumonia.

BackgroundEmerging human adenovirus type 55 (HAdV-55) causes fatal pneumonia in adults. There is a lack of studies on severe pneumonia caused by HAdV-55 in children.MethodsWe conducted a retrospective review of pediatric patients hospitalized at Guangzhou Women and Children’s Medical Center with severe pneumonia from 2013 to 2020 who had human adenovirus (HAdV) detected in throat samples or bronchoalveolar lavage fluid using RT-PCR. The presence of HAdV-55 was determined by PCR amplification of the hypervariable regions of the hexon gene. Demographic, clinical, etiological, and outcome data were collected and analyzed.ResultsOver the eight-year period, HAdV-55 was detected in three severe and six critical pediatric pneumonia patients. None of the patients had any underlying diseases, and had a median age of 18 months (range, 6–108 months). The male to female ratio was 2:1. All patients presented with fever and cough, and three patients presented with wheezing and diarrhea. Six patients had coinfections with other respiratory pathogens, such as bacteria, Mycoplasma pneumoniae and fungi. Three critical patients developed plastic bronchitis (PB). The median lengths of invasive mechanical ventilation and hospital stay of the critical patients were 10 (8, 28.75) days and 25 (13, 32.25) days, respectively. Three critical patients died, although two of them received extracorporeal membrane oxygenation (ECMO) and blood purification. Three surviving patients developed post-infectious bronchiolitis obliterans (PIBO) at the follow-up.ConclusionsHAdV-55 can cause fatal pneumonia in children, and shows a high rate of co-infection with other respiratory pathogens and a poorer prognosis combined with PB. Thus, HAdV-55 may be an important subtype in patients with HAdV-induced pneumonia who develop PIBO.

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

Rehmanniae Radix Preparata (RRP) has been used to management of osteoporotic pain in traditional Chinese medicine trials. However, how RRP exhibits the anti-nociceptive effect remains largely unknown. To this end, estrogen-deficient rats were orally gavaged with aqueous RRP extracts for 12 weeks. The tail flick latency, Von-Frey and formalin assays were employed to evaluate pain sensitization. The administration of RRP alleviates allodynia and hyperalgesia in estrogen-deficient rats. These alterations were associated with a decrease in the expression of substance P (SP), neurokinin-1 receptor (NK-1R), phospho (p)-PI3K, p-protein kinase B (Akt), and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the spinal cord. In addition, RRP improves bone quality in the rats. These results suggest RRP could attenuate pain sensitization and improve bone quality through regulation of PI3K/Akt/TRPV1 signaling pathway during menopause stages. And RRP is considered a novel source of anti-osteoporotic pain drug candidates.

Psoriasis cannot be completely cured and is often difficult to diagnose, which is why the search for new effective therapies and diagnostics is a highly relevant area of research. To identify new therapeutic compounds, the first step is to study the role of various factors underlying the development of psoriasis. One such factor is oxidative stress. In this review, we will consider the role of oxidative stress at different stages of psoriasis development, as well as biomarkers of oxidative stress that can potentially be used in the diagnosis of psoriasis and antioxidants, which are likely to be applied in the treatment of this disease.

MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play critical roles in the regulation of different biological processes, but their underlying mechanisms in diabetes mellitus (DM) are still largely unknown. This study aimed to gain a better understanding of the functions of miRNAs and tsRNAs in the pathogenesis of DM. A high-fat diet (HFD) and streptozocin (STZ)-induced DM rat model was established. Pancreatic tissues were obtained for subsequent studies. The miRNA and tsRNA expression profiles in the DM and control groups were obtained by RNA sequencing and validated with quantitative reverse transcription-PCR (qRT-PCR). Subsequently, bioinformatics methods were used to predict target genes and the biological functions of differentially expressed miRNAs and tsRNAs. We identified 17 miRNAs and 28 tsRNAs that were significantly differentiated between the DM and control group. Subsequently, target genes were predicted for these altered miRNAs and tsRNAs, including Nalcn, Lpin2 and E2f3. These target genes were significantly enriched in localization as well as intracellular and protein binding. In addition, the results of KEGG analysis showed that the target genes were significantly enriched in the Wnt signaling pathway, insulin pathway, MAPK signaling pathway and Hippo signaling pathway. This study revealed the expression profiles of miRNAs and tsRNAs in the pancreas of a DM rat model using small RNA-Seq and predicted the target genes and associated pathways using bioinformatics analysis. Our findings provide a novel aspect in understanding the mechanisms of DM and identify potential targets for the diagnosis and treatment of DM.

In the original publication [...]

Understanding the micro-occurrence mechanism of tight oil has long been a daunting challenge in the exploration and development of unconventional resources. This article discusses the micro-occurrence mechanism of tight oil through continuous extraction by combining thin casting, fluorescent thin sections, environmental scanning electron microscope observations, physical property testing, and X-ray diffraction experiments. The results indicated that in the tight sandstone of the Chang 8 Formation in the Ordos Basin, the average tight oil content was 35.46% for microscale pores, 35.74% for nanoscale pores, and 28.79% for mineral surfaces. Six types of micro-occurrence states of tight oil were identified: emulsion, cluster, throat, star-like, isolation, and thin film forms. Although clay minerals and heavy components dominate the adsorption of tight oil on mineral surfaces, micro-occurrence is fundamentally an oil–rock interaction process. Hence, oil–rock interactions and occurrence states were combined in this study to identify tight oil’s micro-occurrence mechanism. The van der Waals forces of attraction between asphaltene molecules and a mineral surface play a critical role, and minerals with hydroxyl groups can also combine with carboxyl and hydroxyl groups present in tight oil. As a consequence of the adsorption of heavy components by minerals, tight oil components remain in microscale and nanoscale pores with a higher saturation, increased aromatic hydrocarbon content, and greater fluidity. The heterogeneity of the components due to adsorption influences the physical properties and mineralization framework of tight oil reservoirs. These findings suggest that tight oil occurrence results from the coupling of microscopic occurrence and component heterogeneity in microscale and nanoscale pores.

Mitochondrial dysfunction is a described phenomenon for a number of chronic and infectious diseases. At the same time, the question remains open: is this condition a consequence or a cause of the progression of the disease? In this review, we consider the role of the development of mitochondrial dysfunction in the progression of HIV (human immunodeficiency viruses) infection and the onset of AIDS (acquired immunodeficiency syndrome), as well as the direct impact of HIV on mitochondria. In addition, we will touch upon such an important issue as the effect of ART (Antiretroviral Therapy) drugs on mitochondria, since ART is currently the only effective way to curb the progression of HIV in infected patients, and because the identification of potential side effects can help to more consciously approach the development of new drugs in the treatment of HIV infection.

Inorganic carbon dioxide with heavier δ13C values frequently occurs in natural gases or shale gases generated from marine source rocks. To provide a better understanding on the origin of inorganic CO2 associated with hydrocarbon generation, hydrous pyrolysis experiments were conducted utilizing source rocks of different depositional environments and varying carbonate mineral concentrations, at a fixed temperature 350 °C, and lithostatic pressure 50 MPa and fluid pressure 28 MPa for 48 h. Carbon dioxide yields, concentrations in gaseous products, and δ13C values tend to increase in proportion to the carbonate mineral concentrations of the original source rocks. The results showed that carbonate mineral dissolution might be the principal source of inorganic carbon dioxide generated in the experiments. Based on the δ13C values of carbon dioxide produced in the hydrous pyrolysis experiments both in this study and in the literature, we suggest that inorganic CO2 show δ13C values heavier than −8‰, organic CO2 show δ13C values lighter than −16‰, and CO2 with mixed origins show δ13C values ranging from −16 to −8‰. We further discussed the origins of CO2 in the marine Ordovician natural gases of the Ordos Basin, in the marine Miocene CO2-dominated natural gases of the Yinggehai Basin, and in the marine Silurian shale gases of the Sichuan Basin. With a majority of δ13C values higher than −8‰, a major inorganic origin from carbonate mineral dissolution were suggested for CO2 in the natural and shale gases of the above basins.

BackgroundHuman adenovirus (HAdV) lower respiratory tract infections (LRTIs) are prone to severe cases and even cause death in children. Here, we aimed to develop a classification model to predict severity in pediatric patients with HAdV LRTIs using complete blood count (CBC).MethodsThe CBC parameters from pediatric patients with a diagnosis of HAdV LRTIs from 2013 to 2019 were collected during the disease’s course. The data were analyzed as potential predictors for severe cases and were selected using a random forest model.ResultsWe enrolled 1,652 CBC specimens from 1,069 pediatric patients with HAdV LRTIs in the present study. Four hundred and seventy-four patients from 2017 to 2019 were used as the discovery cohort, and 470 patients from 2013 to 2016 were used as the validation cohort. The monocyte ratio (MONO%) was the most obvious difference between the mild and severe groups at onset, and could be used as a marker for the early accurate prediction of the severity [area under the subject operating characteristic curve (AUROC): 0.843]. Four risk factors [MONO%, hematocrit (HCT), red blood cell count (RBC), and platelet count (PLT)] were derived to construct a classification model of severe and mild cases using a random forest model (AUROC: 0.931 vs. 0.903).ConclusionMonocyte ratio can be used as an individual predictor of severe cases in the early stages of HAdV LRTIs. The four risk factors model is a simple and accurate risk assessment tool that can predict severe cases in the early stages of HAdV LRTIs.

Interstitial lung disease (ILD) is a heterogeneous group of pulmonary disorders involving the lung interstitium and distal airways, also known as diffuse lung disease. The genetic defects resulting in alveolar surfactant protein dysfunction are a rare cause of ILD in pediatric patients. We report two unrelated pediatric patients with shortness of breath, dyspnea and hypoxemia, and the chest CT findings including patchy ground-glass opacity in both lung fields, suggestive of diffuse ILD. One patient was a full-term male infant who had shortness of breath a few hours after the birth, and then developed into severe respiratory distress syndrome (RDS). Whole exome sequencing revealed novel compound heterozygous variants in the ABCA3 gene (NM_001,089.3): paternally inherited c.4035+5G > A and c.668T > C (p.M223T), and maternally inherited c.1285+4A > C. The second patient was a 34-month-old boy with onset of chronic repeated cough and hypoxemia at 9 months of age. We unveiled novel compound heterozygous ABCA3 variants (c.704T > C, p.F235S; c.4037_4040del, p.T1346Nfs*15) in this patient. Surfactant protein dysfunction due to bi-allelic mutations in the ABCA3 gene was the cause of ILD in two patients. The novel mutations found in this study expanded the spectrum of known mutations in the ABCA3 gene.

Abstract Goserelin is an effective alternative to surgery or estrogen therapy in prostate cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. However, not all users of goserelin can benefit from it, or some patients are not sensitive to goserelin. The advent of network pharmacology has highlighted the need for accurate treatment and predictive biomarkers. In this study, we successfully to identify 76 potential targets related to the compound of goserelin through network pharmacology approach. We also identified 18 DEGs in breast cancer tissues and 5 DEGs in cells, and 6 DEGs in prostate cancer tissues and 9 DEGs in cells. CRABP2 is the common DEG both in breast and prostate cancer. The risk prediction models constructed with potential prognostic targets of goserelin can successfully predict the prognosis in breast and prostate cancer, especially for very young breast cancer patients. Moreover, seven subgroups in breast cancer and six subgroups in prostate cancer were respectively identified based on consensus clustering using potential prognostic targets of goserelin that significantly influenced survival. The expression of representative genes including CORO1A and ANXA5 in breast and DPP4 in prostate showed strong correlations with clinic-pathological factors. Taken together, the novel signature can facilitate identification of new biomarkers which sensitive to goserelin, increase the using accuracy of goserelin and clarify the classification of disease molecular subtypes in breast and prostate cancer.

Background: Some children hospitalized due to severe community-acquired pneumonia (CAP) require to the pediatric intensive care unit (PICU) because of severe complications. The purpose of this study was to identify the risk factors for mortality in this patient population. Methods: This study evaluated the medical records of 113 hospitalized children with severe CAP, who were transferred to the PICU within 48 h of admission at the Guangzhou Women and Children's Medical Center between 2013 and 2017. Results: The study group consisted of 87 boys (77%) and 26 girls (33%), aged between 1 month and 9 years; 72.6% (82/113) of patients were aged 3 on admission, not receiving corticosteroid therapy prior to admission, the need for mechanical ventilation, septic shock, multi-organ dysfunction (MODS), and acute renal failure (ARF) occurring prior to transfer to the PICU, increased alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, and decreased hemoglobin and albumin (ALB) levels were associated with mortality (P

Accurate estimates of albedo can be crucial for energy balance models of glaciers. A number of algorithms exist which are often site dependent and rely on accurate measurements or estimates of snow depth. Using the well-established COSIMA model we simulate the energy and mass balance of the Laohugou Glacier No.12 in the Qilian Mountains, on the northern fringe of the Qinghai-Tibetan Plateau, a glacier that has been well studied in the past. Using energy flux and mass balance measurements between 2010 and 2015 we were able to validate the model over multiple seasons. Using the original albedo parametrization, the model fails to reproduce the observed mass balance. We show that this is due to the failure to estimate snow depth accurately. We therefore applied two alternative albedo algorithms, one well established example and one new parametrization only dependent on temperature and time since last snow fall. As a result, mass balance simulations improve considerably from a RMSE of 0.53 m w.e. for the original parametrization to 0.39 and 0.19 m w.e. for the uncalibrated established and the new calibrated model respectively. Modelled albedo during the ablation period (NSE = 0.05, R2 = 0.33) is more accurate than during the accumulation period (NSE = −0.37, R2 = 0.04). Testing the new model at another glacier on the Tibetan Plateau shows that a local recalibration of parameters remains necessary to achieve satisfying results. Investigations into the effect of impurities in snow, regional moisture sources and changing surface characteristics with rising temperatures will be crucial for accurate projections into the future.

Abstract Background Perianal Paget’s disease (PPD) is rare and mostly described in clinical literature as case reports or small series. Methods We investigated the clinicopathologic and immunohistochemical features of PPD in a total of 13 cases retrieved from multiple academic institutions. Results The median age at diagnosis was 75 (range 50–86) years. Males were predominant with a male to female ratio of 2.25:1. Four (30.8%) cases were classified as primary PPD due to lack of synchronous or metachronous underlying malignancies, while nine (69.2%) were classified as secondary PPD with concurrent invasive adenocarcinoma (n = 8) or tubular adenoma with high-grade dysplasia (n = 1). Immunohistochemically, there is no differential expression of CK7 or CK20 in Paget’s cells between primary and secondary PPD; however, GCDFP-15 was only positive in primary PPD (3/3 vs. 0/6, P = 0.012), while CDX2 was only positive in secondary PPD (0/3 vs. 7/7, P = 0.008), suggesting different cell origin. All patients received local surgical resection with or without adjuvant therapy. After a median follow-up of 47 months, one patient with secondary PPD (7.7%) died of disease progression from underlying adenocarcinoma. Conclusions PPD occurs in elderly patients with male predominance and is frequently associated with underlying malignancies. Differential expression of CDX2 and GCDFP-15 may help distinguishing primary vs. secondary PPD, which is important for management as the presence of an underlying malignancy impacts clinical course and prognosis. Surgical excision remains the major treatment strategy for PPD. Long-term follow-up is required to monitor the disease recurrence and metastasis.

Hyperuricemia (HUA) is a kind of metabolic disease with high incidence that still needs new countermeasures. Apigenin has uric-lowering and kidney-protective activities, but how apigenin attenuates HUA and renal injury remains largely unexploited. To this end, an acute HUA mouse model was established by intraperitoneal injection of potassium oxazinate and oral administration with hypoxanthine for 7 consecutive days. Apigenin intervention decreased serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin-18 (IL-18), liver xanthine oxidase (XOD), and urine protein levels, and increased serum interleukin-10 (IL-10) and urine UA and CRE levels in HUA mice. Moreover, administration of apigenin to HUA mice prevented renal injury, decreased renal glucose transporter 9 (GLUT9) and urate anion transporter 1 (URAT1) levels, and increased renal organic anion transporter 1 (OAT1). These alterations were associated with an inhibition of IL-6, phospho-janus kinase 2 (P-JAK2), phospho-signal transducer, and activator of transcription 3 (P-STAT3), and suppression of cytokine signaling 3 (SOCS3) expression in the kidneys. Additionally, the molecular docking results showed that apigenin had strong binding capacity with UA transporters and JAK2 proteins. In summary, apigenin could improve UA metabolism and attenuate renal injury through inhibiting UA production, promoting excretion, and suppressing the JAK2/STAT3 signaling pathway in HUA mice. The results suggest that apigenin may be a suitable drug candidate for management of HUA and its associated renal injury.

Worldwide, primary liver cancer is the fourth leading cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of HCC with conventional HCC admixed with areas with sarcomatoid morphology. SHC is an aggressive, rapidly growing tumor with unfavorable prognosis. Pedunculated SHC is an uncommon presentation of SHC. Due to its rarity, much remains unknown about the etiopathogenesis, molecular underpinnings, and treatment of SHC. We present a case of an exophytic SHC arising in a background of cirrhosis in an older adult. A resection was performed, but the patient subsequently developed multiple additional intrahepatic metastatic lesions necessitating further treatment with chemotherapy.

Abstract Flexible transparent conductive electrodes are essential component for flexible optoelectronic devices and have been extensively studied in recent years, while most of the researches are focusing on the electrode itself, few topics in material green and recyclability. In this paper, we demonstrate a high-performance transparent conductive electrode (TCE), based on our previous cracking technology, combined with a green and recyclable substrate, a starch film. It not only shows low R s (less than 1.0 Ω sq−1), high transparency (> 82%, figure of merit ≈ 10,000), but also provides an ultra-smooth morphology and recyclability. Furthermore, a series of biosensors on human joints are demonstrated, showing great sensitivity and mechanical stability.

In this paper, the purification of lanthanum was studied by using zone-refining technology. The equilibrium distribution coefficient of impurities was calculated using a liquidus slope method to reveal impurities’ distribution properties. Meanwhile, the analysis of impurities’ concentration distribution for Fe and Si has been investigated based on the SPIM model. The calculated findings based on SPIM were found to be in good agreement with the experimental results. In addition, the influence of the zone-refining rate and the number of passes on the purification of lanthanum were studied. It was found that after ten times of zone refining with a zone-refining rate of 5 mm/min, the contents of Fe and Si impurities in metal decreased to 4 and 2 ppm, respectively.

The zone refining technology is considered to be one of the most effective means of purifying lanthanum. However, it is tough to obtain the temperature distribution of the molten region through experimental methods. In this study, finite element analysis was used to establish the zone refining simulation model, and the impurity distribution of lanthanum after purification was investigated experimentally. Good agreement between the simulated and experimental results was obtained. The effects of the current and the frequency on the temperature distribution and the width of the region were studied using the simulation model. Through the zone refining experiment, the impurity distributions under different widths of molten region were revealed. Finally, the influence of molten region width on the limiting distribution was calculated by solving the limiting distribution equation.

Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from Curcuma longa that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) in vivo and in vitro. Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.