The Role of TGF-ß/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high incidence and mortality, accounting for approximately 90% of liver cancer. The development of HCC is a complex process involving the abnormal activation or inactivation of multiple signaling pathways. Transforming growth factor-ß (TGF-ß)/Small mothers against decapentaplegic (SMAD) signaling pathway regulates the development of HCC. TGF-ß activates intracellular SMADs protein through membrane receptors, resulting in a series of biological cascades. Accumulating studies have demonstrated that TGF-ß/SMAD signaling plays multiple regulatory functions in HCC. However, there is still controversy about the role of TGF-ß/SMAD in HCC. Because it involves different pathogenic factors, disease stages, and cell microenvironment, as well as upstream and downstream relationships with other signaling pathways. This review will summary the regulatory mechanism of the TGF-ß/SMAD signaling pathway in HCC, involving the regulation of different pathogenic factors, different disease stages, different cell populations, microenvironments, and the interaction with microRNAs. In addition, we also introduced small molecule inhibitors, therapeutic vaccines, and traditional Chinese medicine extracts based on targeting the TGF-ß/SMAD signaling pathway, which will provide future research direction for HCC therapy targeting the TGF-ß/SMAD signaling pathway.

Manganese regulation of COPII condensation controls circulating lipid homeostasis.

Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.

The Role of Vitamin D in Combination Treatment for Patients With Rheumatoid Arthritis.

Background: The aim of this study is to evaluate the clinical efficacy of vitamin D (VitD) supplementation in terms of response to treatment and improvement of disease activity in rheumatoid arthritis (RA). Methods: This study analyzed 1180 RA patients' records treated at Mianyang Central Hospital from February 2015 to July 2019. The patients were allocated into VitD group and control group based on their medical regimens. The outcome measures were primary efficacy, defined as treatment response-based EULAR response criteria in RA, and secondary efficacy, defined as improvement in disease activity indicators. Safety was evaluated according to the incidence of all-cause infections. Results: At month 6, the primary efficacy revealed that there were 22.8% good responders and 19.0% moderate responders in the VitD group, and 22.3% good responders and 22.3% moderate responders in the control group; there were no differences between the two groups (p = 0.754). The similar primary efficacy outcomes were observed at months 3, 12, and >12. The secondary efficacy indicated that there were no differences in most indexes between the two groups at months 1, 3, 6, 12, and >12. The subgroups (based on baseline DAS28 (CRP), glucocorticoids use and disease duration) analysis results suggested that VitD group didn't have the advantage for treating RA. The incidence of infections was similar in the two groups. Conclusion: VitD supplementation did not provide additional benefit for anti-rheumatic treatment. These data supported the need for prospective, randomized, controlled trials to evaluate the role of VitD supplementation in treating RA.

Clinical features and multidisciplinary treatment outcome of COVID-19 pneumonia: A report of three cases.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic threatening global public health. In the current paper, we describe our successful treatment of three COVID-19 pneumonia patients cases including severe cases and cases with mortality risk factors. One 32-year-old male COVID-19 patient was diagnosed with severe COVID-19 pneumonia and moderate ARDS. The second COVID-19 pneumonia patient had a history of diabetes and chronic bronchitis. The third case of COVID-19 pneumonia was an 82-year old female patient. All three cases had severe COVID pneumonia and therefore were aggressively managed with a multidisciplinary and personalized therapeutic approach that included nutritional support, antiviral pharmacotherapy, active control of comorbidities, prevention of complication development and psychological intervention. Our experience highlights the importance of the use of a multidisciplinary therapeutic approach that tailors to the specific condition of the patient in achieving a favorable clinical outcome.

Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome.

Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration, and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension.

Precise and economical dredging model of sediments and its field application: case study of a river heavily polluted by organic matter, nitrogen, and phosphorus.

Environmental dredging is an efficient means to counteract the eutrophication of water bodies caused by endogenous release of nitrogen and/or phosphorus from polluted sediments. The huge operational cost and subsequent disposal cost of the dredged polluted sediments, as well as the adverse effect on the benthic environment caused by excessive dredging, make the currently adopted dredging methods unfavorable. Precise dredging, i.e., determining the dredging depth based on the pollution level, not only significantly decreases the costs but also leaves a uniform favorable environment for benthos. However, there is still no feasible process to make this promising method executable. Taking a river heavily polluted by organic compounds as an example, we proposed an executable precise dredging process, including sediment survey, model establishment, data interpolation, and calculation of dredging amount. Compared with the traditional dredging method, the precise one would save 16 to 45% of cost according to different pollutant removal demands. This precise dredging method was adopted by the National Water Project of China to treat the endogenous pollution of Nanfei River in 2010. This research provides a universal scientific and engineering basis for sediment dredging projects.

Total recovery of nitrogen and phosphorus from three wetland plants by fast pyrolysis technology.

Fast pyrolysis of three wetland plants (Alligator weed, Oenanthe javanica and Typha angustifolia) in a vertical drop fixed bed reactor was investigated in this study. The experiments were carried out at different pyrolysis temperatures, and the maximum bio-oil yields achieved were 42.3%, 40.2% and 43.6% for Alligator weed, Oenanthe javanica and Typha angustifolia, respectively. The elemental composition of the bio-oil and char were analyzed, and the results show that a low temperature was appropriate for the nitrogen and phosphorus enrichment in char. GC-MS analysis shows that nitrogenous compounds, phenols and oxygenates were the main categories in the bio-oil. A series of leaching tests were carried out to examine the recovery of the nitrogen and phosphorus in the char, and the results indicate that significant fractions of nitrogen and phosphorus could be recovered by leaching process.