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Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma with uncontrolled cell proliferation, poor prognosis, and high mortality. The ovarian tumor structural domain (OTU) containing protein 6B (OTUD6B) belongs to the OTU deubiquitin family and is vital in tumor development. However, its expression and biological function in CCA remain unknown. The expression of OTUD6B in CCA was analyzed using TIMER2.0, UALCAN, and GEO databases. MTT, clonal formation assay, immunofluorescence staining, immunohistochemistry staining, and flow cytometry examined the regulation of OTUD6B on cell proliferation, cycle, and apoptosis. The effects of OTUD6B on tumor volume and weight were assessed using the xenograft tumor model. The activities of PTK2 and STAT3 were detected by western blot and CO‐IP. The biological database identified that OTUD6B was upregulated in CCA. In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis. Cell cycle analysis indicated that the cycle stopped at the G0/G1 phase after OTU6B downregulation. Furthermore, OTUD6B knockdown resulted in a decrease in tumor volume and weight in xenograft tumor models. Mechanistically, OTUD6B is involved in the deubiquitination of PTK2. PTK2 further affected the phosphorylation of STAT3 thereby regulating the CCA process. Our study demonstrates that OTUD6B knockdown participates in the ubiquitination of PTK2 and phosphorylation of STAT3 to alleviate the process of CCA. These results suggest that OTUD6B may be a potential new strategy for CCA treatment. [ABSTRACT FROM AUTHOR]

BackgroundsTo study the effects of supplementation of a marine omega-3 poly-unsaturated fatty acids (n3-PUFA) formulation (Omega3Q10) in older adults with hypertension and/or hypercholesterolemia.MethodsA total of 97 people were enrolled to receive 12-week supplementation of either Omega3Q10 (n = 48) or soybean oil (n = 49). Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and hypertension-related symptoms were determined before and after the supplementation.ResultsThere were no baseline differences between the two groups. Omega3Q10 supplementation significantly reduced diastolic blood pressure (DBP) (from 81.6 ± 5.3 mmHg to 79.3 ± 5.2 mmHg, P

BackgroundsRecent experiments suggest that Citrus bergamia extracts could benefit people with dyslipidemia and obesity but this needs to be further validated.MethodsA total of 98 people age-matched older adults (65 years) with elevated blood lipids were enrolled to receive 12-week supplementation of a Citrus bergamia extracts-based formulation (CitriCholess)(n = 48) and placebo (n = 50).ResultsNo group differences were found in baseline bodyweight, body mass index (BMI), blood cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and glucose levels. CitriCholess supplementation resulted in lower levels than placebo in TG (1.83 ± 0.92 vs. 1.95 ± 1.34 mmol/L, P = 0.612), TC (5.14 ± 0.98 vs. 5.44 ± 0.77 mmol/L, P = 0.097), and LDL-C (3.13 ± 0.74 vs. 3.43 ± 0.62 mmol/L, P = 0.032). Compared to placebo, CitriCholess also resulted in greater reductions in body weight (-0.604 ± 0.939 vs. 0.06 ± 0.74 kg, P

The development of anti-rhythmic carbonate reservoirs in the Middle East often encounters challenges such as water hold-up and reverse coning during the water injection process, leading to premature water breakthrough and various water-out issues. The unclear understanding of these phenomena, attributed to strong reservoir heterogeneity, results in a relatively low recovery degree in water injection development. This paper investigates the mechanisms behind water hold-up and reverse coning phenomena, offering detailed solutions. Numerical models of the oil reservoirs were developed, and an extensive study of influencing factors, including reservoir types, Kv/Kh, water injection pressure differential, wettability, and perforation position, was conducted to unveil the underlying mechanisms. Key findings indicate that the water hold-up phenomenon is influenced by capillary force barriers due to wettability and high-perm streaks, while the reverse coning phenomenon depends on the combined forces of gravity, capillary force and downward production differential among which downward production differential is the dominant factor compared to capillary force and gravity. The study also proposes a differential perforation principle tailored to different water-out types to enhance vertical sweep efficiency. The differential perforation principle is as follows: the optimal perforation position is at top layer and the optimal perforation length approximately accounts for 1/4 of the total oil layer thickness for water-out in bottom; the avoidance perforation height in top accounts for 1/6 of the total oil layer thickness and the optimal perforation length approximately accounts for 1/2 of the total oil layer thickness for water-out in top; the avoidance perforation height in top and bottom accounts for 1/5 and 2/5 of the total oil layer thickness respectively for water-out in both top and bottom. [ABSTRACT FROM AUTHOR]

Vincristine (VCR) is a microtubule‐destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte‐sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte. [ABSTRACT FROM AUTHOR]

Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47-88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs.

Objective To investigate differences in the relationship between degree and type of obesity and serum amino acids in type 2 diabetes (T2DM). Methods This was a cross-sectional study. T2DM patients who visited Endocrinology Department in the First People's Hospital of Yunnan Province from December 2016 to June 2018 were retrospectively enrolled. Waist circumference, height and weight were collected, and body mass index (BMI) was calculated. Serum branched chain amino acids (BCAA) and aromatic amino acids, glycosylated hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-C), uric acid, triglycerides (TG), fasting plasma glucose (FPG), and fasting insulin (FINS) were measured, and homeostasis model homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. T2DM patients were divided into normal weight, overweight and obese groups based on BMI; additionally, T2DM patients were divided into non abdominal obesity (NAO) and abdominal obesity (AO) groups based on waist circumference. Using t-test/one-way analysis of variances (ANOVA), non-parametric rank sum test, χ² tests for inter group comparison. Pearson/Spearman correlation analysis was used to analyze serum amino acid levels and metabolic indicators, as well as pancreatic islets β cell function and insulin resistance. Multiple linear regression analysis was used to analyze the relevant influencing factors of tryptophan. The predictive effect of serum amino acids on the degree and type of obesity was analyzed by means of the receiver operating characteristic (ROC) curve. Results A total of 97 T2DM patients were included. Among them, there were 33 cases in the normal weight group, 42 cases in the overweight group, and 22 cases in the obese group. There were 41 cases in the NAO group and 56 cases in the AO group. Compared with normal weight group, T2DM patients in obese group had significantly lowered levels of HbA1c and HDL-C; elevated levels of uric acid, TG, HOMA-IR, serum concentrations of BCAA isoleucine, aromatic amino acids tryptophan and tyrosine (P<0.05). T2DM patients in AO group had significantly lower levels of HDL-C and higher levels of TG, serum concentrations of tryptophan than those in NAO group (P<0.05). Serum levels of BCAA leucine, isoleucine, valine and aromatic amino acids tryptophan, tyrosine and phenylalanine were all positively correlated with BMI (P<0.05), whereas serum tryptophan level was also positively correlated with waist circumference (P=0.036) in patients with T2DM. In addition, multiple linear regression analysis showed that waist circumference was the influencing factor of serum tryptophan (P=0.048). ROC analysis showed that serum tryptophan had a certain predictive value for obesity and AO, and the areas under the curve were 0.645 (95%CI 0.533-0.758, P=0.019) and 0.629 (95%CI 0.517-0.742, P=0.029), respectively. Conclusions There is a difference between degree and type of obesity with serum BCAA and aromatic amino acids in T2DM patients. Tryptophan is not only related to the accumulation of body fat, but also may be related to the pattern of fat deposition. [ABSTRACT FROM AUTHOR]

Reorientation fractures may be formed in soft and shallow formations during fracturing stimulation and then affect well productivity. The principal focus of this study is on the productivity analysis for a horizontal well with multiple reorientation fractures in an anisotropic reservoir. Combining the nodal analysis technique and fracture-wing method, a semi-analytical model for a horizontal well with multiple finite-conductivity reorientation fractures was established to calculate its dimensionless productivity index and derivative for production evaluation. A classic case in the literature was selected to verify the accuracy of our semi-analytical solution and the verification indicates this new solution is reliable. Results show that for a fixed fracture configuration the dimensionless productivity index of the proposed model first goes up and then remains constant with the increase of fracture conductivity, and optimal fracture conductivity can be determined on derivative curves. Strong permeability anisotropy is a negative factor for well production and the productivity index gradually decreases with the increase of anisotropic factor. As principal fracture angle goes up, horizontal well’s productivity index increases correspondingly. However, the effect of reoriented fracture angle on the productivity index is not as strong as that of principal fracture angle. When reoriented fracture angle is smaller than principal fracture angle, reoriented factor should be as low as possible to achieve optimal productivity index. Meanwhile, well productivity index rises up with the increase of fracture number and fracture spacing, but the horizontal well has optimal reorientation fracture number and fracture spacing to get the economical productivity. Furthermore, the influence of the rotation of one central reorientation fracture on productivity index is weaker than that caused by the rotation of one external reorientation fracture. In addition, the asymmetrical distribution of one or more reorientation fractures slightly affects the productivity index when fracture conductivity is high enough.

In this work, we report on a significant breakthrough in fabricating the critical tunnel oxide layer of tunnel oxide passivated contacts (TOPCon) high‐efficiency solar cells compatible with high‐volume manufacturing. We show that the tunnel oxide can be controlled at the atomic scale, enabled by an innovative tube‐type industrial plasma‐assisted atomic layer deposition (PEALD) method. In combination with an in situ doped poly‐Si (n+) layer grown by plasma‐enhanced chemical vapor deposition, a uniform, ultrathin ~1.3 nm SiOx layer is obtained at the c‐Si/SiOx/poly‐Si (n+) interface. Extremely low recombination current densities down to 2.8 fA/cm2 and an implied open‐circuit voltage (iVoc) as high as 759 mV are achieved, comparable to state‐of‐the‐art laboratory results. The developed tube‐type PEALD SiOx is applied to industrial TOPCon solar cells resulting in a solar cell efficiency and open‐circuit voltage of up to 24.2% and 710 mV, respectively. The tunnel oxide process window is about 2.4 Å, highlighting the importance of precisely controlling the tunnel oxide thickness at the atomic scale for TOPCon solar cells. The newly developed tube‐type industrial PEALD SiOx method opens up a promising new route toward mass production of high‐efficiency industrial TOPCon solar cells. Furthermore, the developed tube‐type PEALD method can easily be integrated with the industrial tube‐type plasma‐enhanced chemical vapor deposition (PECVD) method, thus enabling the deposition of all thin film layers in TOPCon solar cells in one integrated PEALD/PECVD system. This significantly simplifies manufacturing complexity and fosters the commercialization of next‐generation high‐efficiency industrial TOPCon solar cells. [ABSTRACT FROM AUTHOR]