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Baphicacanthus cusia (Nees) Bremek has a rich historical significance in China. Its stems and leaves have been used for traditional Chinese medicine or a dye called Qing-Dai in Chinese, while its roots are referred to as Nan-Ban-Lan-Gen in Chinese after processing. Both have been recognized and documented in the Chinese Pharmacopoeia. Modern pharmacological studies have revealed that B. cusia has numerous bioactive properties, such as antitumor, antiviral, anti-inflammatory, antioxidant, hepatoprotective, and neuroprotective properties. Moreover, B. cusia has been employed in clinical settings for its antitumor activity. The pivotal bioactive compounds in B. cusia are indirubin, indigo, and tryptanthrin. These potent substances and their derivatives demonstrate antitumor effects through inducing cell cycle arrest, triggering programmed cell death, inhibiting metastasis, and overcoming multidrug resistance. Nonetheless, the metabolic pathway of these compounds, particularly indole alkaloids, in B. cusia remains inadequately investigated. To increase the production of indole alkaloids such as indirubin and indigo, various biosynthetic approaches are employed. Consequently, this review discusses the bioactive compounds present in B. cusia, and elucidates their antitumor mechanisms, metabolism, and biosynthesis pathway. Existing studies indicate that B. cusia is a crucial medicinal plant harboring numerous biologically active substances, and its exploitation and application hold significant potential for substantial economic gains.

Background: Progesterone can inhibit intestinal smooth muscle contraction; however, the specific mechanism remains unclear. Besides smooth muscle cells, smooth muscle has two important mesenchymal cells, namely interstitial cells of Cajal (ICC) and PDGFRα+ cells, which induce the contraction and relaxation of smooth muscles. We aimed to explore the regulation of PDGFRα+ cells and ICC in progesterone-mediated colon slow transit in pregnant mice. Methods: Colon transit experiments were performed in vivo and in vitro to observe slow colon transit. The expression of PDGFRα and c-KIT was detected by Western blot, RT-PCR, and immunofluorescence. An isometric tension experiment was performed to investigate smooth muscle contractions. Results: The colon transit time in pregnant mice was longer than that in non-pregnant mice. Progesterone significantly blocks colonic smooth muscle contractions. However, when the relaxation and contraction of PDGFRα+ cells and ICC are blocked, progesterone cannot inhibit smooth muscle contraction. When the function of only PDGFRα+ cells are blocked, progesterone has a more obvious inhibitory effect on smooth muscle in the non-pregnant group than that in the pregnant group. However, when ICC alone was blocked, progesterone inhibited smooth muscle contractions more clearly in pregnant mice. The protein and mRNA expression of PDGFRα was higher and c-KIT was lower in pregnant mice. PDGFRα+ cells and ICC from smooth muscle all co-localize progesterone receptors. Conclusions: Under the regulation of progesterone, the relaxation function of PDGFRα+ cells is enhanced and the contraction function of ICC is weakened, leading to the slow colon transit of pregnant mice.

Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs).Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice.Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8 nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60 h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC–PLGA–PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094 μg/mL, whereas this of free rifapentine was 0.25 μg/mL.Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.

Abstract Background To investigate the efficacy and safety of interval debulking surgery (IDS) combined with dense hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in Chinese patients with FIGO stage III serous epithelial ovarian cancer (EOC). Methods This retrospective single-center study reviewed the demographic and clinical data of 197 patients with primary FIGO stage III serous EOC who were treated with IDS with (n = 121) or without (n = 76, control group) dense HIPEC between January 2012 and April 2017. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was the occurrence of adverse events. Results The median PFS was 24 months in the IDS plus dense HIPEC group, whereas it was 19 months in the IDS alone group (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.33–0.65, p = 0.000). The median OS in patients treated with IDS plus dense HIPEC (51 months) was significantly longer than that in patients treated with IDS alone (40 months, HR 0.52, 95% CI: 0.35–0.78, p = 0.001). The demographic and preoperative clinical characteristics of these two groups were comparable (p > 0.05). In the IDS alone group, no adverse events were recorded in 42 (55.3%) of the 76 patients, and 14 (18.4%) patients were reported to have grade III/IV adverse events. In the IDS plus dense HIPEC group, no adverse events were recorded in 55 (45.5%) of the 121 patients, and 23 (19.0%) patients were reported to have grade III/IV adverse events. No postoperative deaths occurred within 30 days in either group and neither did severe fatal complications in the IDS plus dense HIPEC group. Conclusions IDS plus dense HIPEC with cisplatin in Chinese patients with FIGO stage III serous EOC is associated with improved survival and is reasonably well tolerated by patients.

The seal is the key part of the cone bit. To reduce the failure probability, a new seal was designed and studied. The sealing performance and structure optimization of the X-O composite seal was analyzed and compared by finite-element analysis. The stress and contact pressure were analyzed to establish the main structural parameters that affect sealing performance and the direction of the structural optimization. By optimizing these structural parameters, including the height, and the radial and axial arc radii, an optimized structure is obtained. The results show that (1) the X-O composite seal can meet the seal requirement, the excessive height of the X seal ring is the root cause of the uneven distribution of stress, pressure, and distortion. (2) A new seal structure is obtained, the distribution of pressure and stress is reasonable and even, and the values of stress and pressure are reduced to avoid distortion and reduce the wear. Finally, the field test results of the X-O composite seal of cone bit showed that the service life of the bit bearing increased by 16% on average and the drilling efficiency increased by 11% on average compared with the original cone bit with the O seal ring.

Hydraulic disturbance of a vibrator is the main cause of distortion of the vibroseis geophysical exploration signal that is caused by high-frequency fluid vibration during servo valve cavity commutation. This disturbance is closely related to the structure, size, and arrangement of the hydraulic flow path of the vibrator reaction mass. In this work, a vibrator disturbance–suppression mechanism was examined, an experimental study was carried out on an improved design of the hydraulic flow channel, and the source of the hydraulic disturbance of the horizontal channel vibrator was determined. The vibrator hydraulic flow channel was changed to a vertical flow channel in the piston rod. In addition, the structure of the track was designed, and the angle of the oil inlet of the piston rod was tested at 0°, 45°, and 90°. Then, the fluid flow state and fluid–solid coupling analysis method were used to improve the vibration-suppression effect of the vibrator. The results showed that the optimal oil inlet angle is 90°, for which the turbulent intensity of the oil inlet is the smallest, the pressure drop loss is reduced, and the influence of the oil flow on the piston rod deformation is minimal. The vibration reaction mass test of the vibrator showed that the disturbance inhibition rate of the piston rod with a 90° inlet structure design reaches 64.087%; the hydraulic disturbance had the best suppression effect and effectively reduced the distortion of the seismic prospecting signals with this oil inlet angle, improving the quality and efficiency of oil and gas exploration.

Abstract Background Dyskeratosis congenita (DC) is a rare heritable bone marrow failure syndrome that is associated with telomere dysfunction, and has high genetic heterogeneity and varied features. Objective This study aimed to identify the underlying genetic etiology of a DC family with more severe symptoms in the younger generation and to explore the relationship between the genetic causes and the severity of DC phenotype. Methods Whole‐exome sequencing was performed on the proband to screen the candidate causative gene. The protein structure was then predicted by SWISS‐MODEL software. Telomere length (TL) assay was performed on family members along with large‐scale population controls. The prenatal diagnosis (PND) was performed on the fetus of parents with secondary pregnancy. Results Novel heterozygous mutations in TERT (NM_198253.2), c.1796G>A (p.Arg599Gln), c.2839T>C (p.Ser947Pro), and c.3346G>C (p.Glu1116Gln) were identified in the proband. His TL was below the first percentile of the peers, which also appeared on the fetus with epidermal dyskeratosis through PND. The TL data of large‐scale population and members of the DC family implied the accumulation of telomere erosion in successive generations in this family. Conclusions Our study identified three clinical pathologic TERT mutations and implied that telomere erosion might be accumulated through successive generations, contributing to the severity of DC in the younger generation.

The seismic vibrator has become a main energy source for land seismic exploration. For a seismic vibrator, a piston is installed in the vertical direction in the reaction mass, and the reaction mass moves up and down along the piston. Because of vibrator dynamic disturbances in the reaction mass and baseplate system, the vibrator output force is contaminated by harmonic distortion. This distorted output force results in poor quality of seismic data. This paper studies the dynamics and disturbances of the piston as well as the reaction mass. The results show that the reaction mass disturbance is mainly caused by the horizontal oil flow inlet going to the reaction mass chamber. Precisely speaking, the ideal vertical motion of the reaction mass is disturbed by a combination of a reaction mass rotational motion along the piston and a bending motion of the piston. Changing the oil flow inlet from the horizontal direction to the vertical direction significantly reduces these disturbances. In the disturbance test of the vertical oil flow inlet, the disturbance of the reaction mass in XOZ and YOZ is reduced by 73.943% and 54.232%, respectively, and the disturbance of the vibrator is obviously weakened. The motion of the reaction mass is close to the ideal vertical direction. This change of the oil flow inlet direction further improves the accuracy and reliability of the vibrator output force.

Objective: Thyroid autoimmunity (TA) is the most prevalent autoimmune disease in women of reproductive age and is often accompanied by subclinical hypothyroidism (SCH). Both TA and SCH have been associated with adverse pregnancy outcomes, but their relative influence is unclear. Therefore, we carried out a meta-analysis to evaluate the sole effect of TA on pregnancy outcomes in euthyroid women undergoing assisted reproductive technology. Materials and Methods: Literature searches were conducted on Pubmed, EMBASE, and the Cochrane Controlled Trials Register Database from inception to May 2014. Results: In euthyroid women whose SCH status is unknown, those with positive antithyroid antibodies (ATA) had a higher miscarriage rate [pooled relative risk (RR) = 1.638; 95% confidence interval (CI), 1.228–2.185] and a lower delivery rate (pooled RR = 0.856; 95% CI, 0.759–0.965) than those with negative ATA. Clinical pregnancy rates were similar between groups. However, clinical pregnancy rate, miscarriage rate, and delivery rate were all comparable between ATA-positive and ATA-negative euthyroid women without SCH. Conclusion: TA per se does not impair assisted reproductive treatment outcomes in women without SCH.

BACKGROUND:Frozen-thawed embryo transfer (FET) has become a routine procedure in assisted reproductive technology (ART). In FET, although blastocysts cultured from thawed cleavage-stage embryos are associated with better perinatal outcomes. it may increase cycle cancellation due to no suitable embryo to transfer. The overall clinical outcomes following transfer of thawed cleavage-stage FET and blastocysts cultured from thawed cleavage-stage embryos in young and advanced age patients remains unclear. Therefore, we aimed to identify the optimal FET strategy in young and advanced age women who undergo FET. METHODS:This retrospective study included 16,387 thaw cycles. We retrospectively analyzed data of couples who had completed the first FET cycle. Two FET strategies were studied: transfer of thawed cleavage-stage embryos (strategy A) or blastocysts cultured from thawed cleavage-stage embryos (strategy B). The clinical and neonatal outcomes of two FET strategies were compared in young (

Background: Observational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown. Methods: We investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two‐sample Mendelian randomization (MR) approach. The inverse variance‐weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method. Results: Our research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions. Conclusions: The findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions. [ABSTRACT FROM AUTHOR]