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Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3–5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.

It is critical to understand the factors that are associated with nasopharyngeal carcinoma (NPC) progression, metastasis and response to therapy. Here, the authors analyse primary and metastatic NPC samples using bulk and single-cell sequencing, and find two distinct evolutionary routes that lead to metastasis.

Abstract Background Post-menopausal hypertension has been attributed solely to declining estrogen levels. The purpose of the research is to elucidate the mechanism by which follicle stimulating hormone(FSH) increases renin production involved in the regulation of blood pressure. Methods The expression of follicle stimulating hormone receptors (FSHRs) in renal juxtaglomerular cells and a As4.1 juxtaglomerular mouse cell line was evaluated. We established a mouse model by ovariectomy (OVX). Ovariectomized mice were treated with gonadotropin-releasing hormone agonist (GnRHa) (OVX + GnRHa). Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH (OVX + E + FSH). Results We found that FSHR was expressed in mouse renal juxtaglomerular cells labeled by renin antibody and in As4.1 cells. FSH promoted renin synthesis via Gsα-coupled FSHRs that activated protein kinase A, cyclic adenosine monophosphate(cAMP) response element-binding protein, extracellular signal-regulated kinase (Erk1/2), Protein kinase B(AKT), and c-Jun N-terminal kinase signaling pathways in As4.1 cells. We found increased serum FSH levels in the ovariectomized mouse with concurrent increases in renin, angiotensin II, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP). Additionally, increases in serum renin, angiotensin II, HR, SBP, DBP, and MAP were reduced by the additional injection of GnRHa. Exogenous FSH administration completely reversed decreases in renin, angiotensin II, HR, SBP, DBP, and MAP even in mice that received physiological doses of estrogen to maintain normal estradiol levels. Conclusions Elevated FSH stimulates renin production involving a mechanism that may be relevant to the expression of FSH receptors in renal juxtaglomerular cells.

Abstract Seed deterioration during rice seed storage can lead to seed vigor loss, which adversely affects agricultural production, the long-term preservation of germplasm resources, and the conservation of species diversity. However, the mechanisms underlying seed vigor maintenance remain largely unknown. In this study, 16 hybrid rice combinations were created using four sterile lines and four restorer lines that have been widely planted in southern China. Following artificial aging and natural aging treatments, germination percentage and metabolomics analysis by gas chromatography–mass spectrometry was used to identify the metabolite markers that could accurately reflect the degree of aging of the hybrid rice seeds. Significant differences in the degree of seed deterioration were observed among the 16 hybrid rice combinations tested, with each hybrid combination having a different germination percentage after storage. The hybrid rice combination with the storage-resistant restorer line Guanghui122 exhibited the highest germination percentage under both natural and artificial storage. A total of 89 metabolic peaks and 56 metabolites were identified, most of which were related to primary metabolism. Interestingly, the content of galactose, gluconic acid, fructose and glycerol in the seeds increased significantly during the aging process. Absolute quantification indicated that galactose and gluconic acid were highly significantly negatively correlated with the germination percentage of the seeds under the different aging treatments. The galactose content was significantly positively correlated with gluconic acid content. Additionally, glycerol showed a significant negative correlation with the germination percentage in most hybrid combinations. Based on the metabolomics analysis, metabolite markers that could accurately reflect the aging degree of hybrid rice seeds were identified. Galactose and gluconic acid were highly significantly negatively correlated with the germination percentage of the seeds, which suggested that these metabolites could constitute potential metabolic markers of seed vigor and aging. These findings are of great significance for the rapid and accurate evaluation of seed aging degree, the determination of seed quality, and the development of molecular breeding approaches for high-vigor rice seeds.

Abstract Background Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost‐effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD‐L1) test on the cost‐effectiveness is also unknown. The current study assessed the cost‐effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers’ perspective. Materials and Methods A literature‐based Markov model was conducted using KEYNOTE‐189 trial data to compare cost and quality‐adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro‐chemotherapy combination and chemotherapy strategy without PD‐L1 test, and treatment strategy according to their PD‐L1 status. Results In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD‐L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD‐L1 test strategy. In the PD‐L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD‐L1 test strategy. Lowering Pembro price can also partly decrease the ICERs. Conclusion Compared with chemotherapy, the combination strategy is not cost‐effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD‐L1 test for patient selection and price reduction could improve the cost‐effective probabilities of immunotherapy for nonsquamous NSCLC.

AIM: To explore the effect of vitrectomy combined with gas-liquid exchange on the treatment of posterior segment nonmagnetic foreign body and best corrected visual acuity(BCVA)after operation.METHODS: Totally 84 patients(86 eyes)were enrolled in this study. They were divided into observation group and control group, each group with 42 cases(43 eyes). The control group was treated with vitrectomy alone, and the observation group was treated with gas-liquid exchange combined with vitrectomy. The operation time, foreign body clearance rate, retinal recovery rate, BCVA level, macular central retinal thickness, and complications were compared between two groups. RESULTS: The operation time and complication rate of the observation group were lower than those of the control group. The rate of foreign body clearance and retinal reattachment was higher than that of the control group(PPCONCLUSION:Gas-liquid exchange combined with vitrectomy for the treatment of non-magnetic foreign bodies in the posterior segment of the eye is effective, which can improve the postoperative visual acuity, the retinal edema and reduce surgical complications.

Long noncoding RNAs (lncRNAs) have been identified to play increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. LncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is demonstrated to decrease in several cancers. However, it is still unknown whether lncRNA NBR2 is involved in hepatocellular carcinoma and autophagy. We found that HCC cases with lower NBR2 expression had significantly worse overall survival than those with higher NBR2 expression in advanced patients. And the expression of NBR2 was negatively correlated with the degree of malignancy of HCC cell lines and differentiation of hepatocellular carcinoma. Besides, NBR2 inhibited the proliferation, invasion, and migration of liver cancer cells. We further found that NBR2 repressed cytoprotective autophagy to restrain HCC cell proliferation. Moreover, NBR2 inhibited Beclin 1-dependent autophagy through ERK and JNK pathways. Taken together, NBR2 suppressed autophagy-induced cell proliferation at least partly through ERK and JNK pathways. These data indicated that NBR2 served as a tumor suppressor gene in hepatocellular carcinoma. The current study provides a novel insight and treatment strategy for hepatocellular carcinoma.

Neurogenic erectile dysfunction (NED) is an inevitable postoperative disease of cavernous nerve injury which will lead to various pathophysiological changes in the corpus cavernosum and dorsal penile nerve caused by radical prostatectomy (RP). Although serval years of clinical application of HJIG I granules (HJIG), an innovative formulation, has demonstrated its reliable clinical efficacy against NED, the mechanism of HJIG remains unclear. This study aimed to assess the neuroprotective effect of HJIG, to repair damaged nerves in a rat model of bilateral cavernous nerve injury (BCNI) in vivo and their effects on neurites of major pelvic ganglia (MPG) regeneration and Schwann cells (SCs) proliferation in vitro. Rats were divided into five groups randomly: normal control (NC), BCNI-induced ED model (M), M + low-dose HJIG (HL), M + medium-dose HJIG (HM), and M + high-dose HJIG (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after a standard NED animal model. Our data revealed that administration of HJIG improved NED that was detected by intracavernous pressure (ICP) in a dose-dependent manner. The haematoxylin-eosin (HE) and Immunofluorescence (IF) staining demonstrated that HJIG ameliorate the shape of penis and induced the protein synthesis of GAP43, NF200, S100, and nNOS. NF200 and S100 level were also detected by western blotting. Moreover, HJIG (0.78 mg/mL) markedly increased SCs viability and promoted neurites regeneration of MPG. These findings provide new insights into the NED therapy by HJIG.

Sensorineural hearing impairment is a common sensory deficit in children and more than 50% of these cases are caused by genetic etiologies, that is, hereditary hearing impairment (HHI). Recent advances in genomic medicine have revolutionized the diagnostics of, and counseling for, HHI, including preimplantation genetic diagnosis (PGD), thus providing parents-to-be with better reproductive choices. Over the past decade, we have performed PGD using the amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) technique in 11 couples with a history of HHI, namely eight with GJB2 variants, one with OTOF variants, one with SLC26A4 variants, and one with an MITF variant. We demonstrated that PGD can be successfully applied to HHI of different inheritance modes, namely autosomal dominant or recessive, and phenotypes, namely syndromic or non-syndromic HHI. However, certain ethical concerns warrant scrutiny before PGD can be widely applied to at-risk couples with a history of HHI.

Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro. PDGF-BB at 5, 10, or 20 ng/ml altered CCSMC morphology from the original elongated, spindle shape to a broader shape and promoted the synthetic phenotype and expression of the related proteins vimentin and collagen-I, while inhibiting the contractile phenotype and expression of the related proteins smooth muscle (SM) α-actin (α-SMA) and desmin. Inhibition of PDGFR activity via siRNA or the PDGFR inhibitor crenolanib inhibited vimentin and collagen-I expression, increased α-SMA and desmin expression, and considerably inhibited serine-threonine protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. STAT3 knockdown promoted the contractile phenotype, inhibited vimentin and collagen-I expression, and increased α-SMA and desmin expression, whereas AKT knockdown did not affect phenotype-associated proteins. STAT3 overexpression in CCSMC cells weakened the suppressive effect of PDGFR inhibition on the morphology and phenotypic transformation induced by PDGF-BB. Through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy.

This paper presents a study on the interaction effect of particles on nanofluid flow through microtubes of radii 140 and 231 μm. A flow model is firstly built and solved by using the marching implicit (MI) procedure. A stable water-based magnetite (Fe3O4) nanofluid is then prepared, and a flow test system is further designed, so as to investigate the role of particle interaction in microflow characteristics. The results reveal that the particle interaction effect is to increase the pressure drop (or reduce the volume flow rate). The role of particle interaction becomes more significant when the particle volume fraction increases or the tube size decreases. The collision and friction between particles and tube wall could be found to dominate the role as a major interaction for a sufficiently small tube size and to result in a dramatic increase in effective viscosity. [ABSTRACT FROM AUTHOR]

The article presents a study that explores the efficacy and safety of combination salmeterol/fluticasone propionate (SFCs) inhalation in the management of Chinese chronic obstructive pulmonary disease patients. The subjects were people who never smoke, former smokers and current smokers. The results revealed that SFC therapy achieved sustained improvement in lung function, quality of life and control of symptoms which was well tolerated among patients.