Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation.

OBJECTIVE: To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS: Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS: iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION: Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation，indicating it may be a potential treatment for inflammatory bone loss does in AS.

VEGF counteracts shear stress-determined arterial fate specification during capillary remodeling.

A key feature of arteriogenesis is capillary-to-arterial endothelial cell fate transition. Although a number of studies in the past two decades suggested this process is driven by VEGF activation of Notch signaling, how arteriogenesis is regulated remains poorly understood. Here we report that arterial specification is mediated by fluid shear stress (FSS) independent of VEGFR2 signaling and that a decline in VEGFR2 signaling is required for arteriogenesis to fully take place. VEGF does not induce arterial fate in capillary ECs and, instead, counteracts FSS-driven capillary-to-arterial cell fate transition. Mechanistically, FSS-driven arterial program involves both Notch-dependent and Notch-independent events. Sox17 is the key mediator of the FSS-induced arterial specification and a target of VEGF-FSS competition. These findings suggest a new paradigm of VEGF-FSS crosstalk coordinating angiogenesis, arteriogenesis and capillary maintenance.

Response to belimumab among patients with refractory lupus nephritis: a real-world observational retrospective multicenter study.

OBJECTIVES: Belimumab is a biological agent approved for the treatment of active lupus nephritis (LN), but its efficacy on refractory lupus nephritis (LN) is unknown. This study aims to evaluate the efficacy and safety of belimumab in Chinese patients with refractory LN. METHODS: This multicenter, observational, and retrospective study enrolled patients with refractory LN who failed induction therapy with steroids, cyclophosphamide, mycophenolate, and calcineurin inhibitors and received 24-week belimumab treatment before data analysis. Treatment outcomes include the overall clinical response (physician judgment, disease activity, organ damage) and renal response (complete renal response, partial renal response, no renal response). Laboratory indices and adverse events were recorded as well. RESULTS: Of the 45 patients enrolled in the study, 6 (13.3%) achieved complete renal response, 19 (42.2%) achieved partial renal response, and the overall renal response rate was 55.6%. Median rSLEDAI decreased from 12 (IQR 8-12) at baseline to 8 (IQR 4-8) (p < 0.0001), 4 (IQR 4-8) (p < 0.0001) at 12 and 24 weeks. Mean urinary protein decreased more than 50% from 3.2 g/24 h at baseline to 1.0 g/24 h at 24 weeks (p < 0.0001). The conditions of hypoalbuminemia and hypocomplementemia had also gradually improved. The levels of autoantibodies showed a significant downward trend. Additionally, 9 (20.0%) patients successfully reduced the dosage of prednisone to a safe range, and 3 of them achieved their treatment goal of prednisone cessation. The mean prednisone dosage decreased from 32.7 mg/day at baseline to 18.6 mg/day (p < 0.0001), 13.3 mg/day (p < 0.0001) at 12 and 24 weeks. There were 3 adverse events reported, including 2 cases of infection, and 1 case of allergy. No serious events occurred during the follow-up. CONCLUSIONS: Belimumab is effective and safe when used in clinical practice, which can be considered as an add-on therapy for refractory LN. Key Points • A multicenter observational study in the real clinical settings of China. • First revealed the efficacy and safety of belimumab in Chinese patients with refractory LN.

Discovery and Identification of a Novel Tag of HlyA60 for Protein Active Aggregate Formation in Escherichia coli.

The strategy of active aggregation tag fusion expression with target proteins can solve the problems of restricted expression, inefficient purification, and laborious immobilization faced in the production of recombinant proteins in Escherichia coli. We localized a novel active aggregation peptide HlyA60 from the hemolysin A secretion system, which can effectively induce aggregate formation with satisfactory protein activities in E. coli after fusion expression with the protein of interest. Based on structural prediction and surface properties, the process of active aggregation of HlyA60 through electrostatic interactions and hydrophobic interactions was analyzed. To investigate the potential application of HlyA60 as an efficient aggregation tag, it was fused with acetyl xylan esterase and lipase A, separately. The resulting fusion proteins demonstrated active aggregation rates of 97.6 and 66.7%, respectively, leading to 1.9-fold and 1.7-fold increases in bacterial density at the end of fermentation. The AXE-HlyA60 fusion protein, which exhibited superior performance, was subjected to purification and immobilization. It was able to achieve column-free purification with an impressive 98.8% recovery and in situ immobilization; the immobilization enabled 30 cycles of reactions to take place with 85% residual activity maintained. Our findings provide a novel tool for efficiently producing recombinant proteins in E. coli.

Effects of aqueous extracts and volatile oils prepared from Huaxiang Anshen decoction on p-chlorophenylalanine-induced insomnia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Insomnia occurs frequently in modern society, and its common symptoms include difficulty in falling asleep and decreased sleep quality and time, memory, and attention. With the advantages of having few side-effects and reduced drug-dependence, a compound traditional Chinese medicine (TCM) prescription called Huaxiang Anshen Decoction (HAD) has been widely used in clinical practice in China mainly for primary insomnia treatment. Although the effects of volatile oils from TCM herbs have been increasingly reported, volatile oils in HAD are conventionally neglected because of its preparation process and clinical usage. Therefore, exploring the anti-insomnia effects of volatile oils from HAD is of great importance. AIM OF THE STUDY: The sedative and hypnotic effects of the conventional aqueous extracts, the volatile oils from HAD, and their combinations were investigated. METHODS: The main components in HAD volatile oils (HAD-Oils), were analyzed through gas chromatography-mass spectrometry (GC-MS). The HAD volatile oil inclusion complex (HAD-OIC) was prepared with ß-cyclodextrin, and characterized. P-chlorophenylalanine (PCPA) was used to induce insomnia mice model and the test groups of HAD aqueous extract (HAD-AE), HAD-OIC and their combination (AE-OIC). An open field test was used in evaluating the mice's activities, and the levels of 5-hydroxytryptamine (5-HT) in mice sera, glutamate (Glu) in the hypothalamus, and γ-aminobutyric acid (γ-GABA) and dopamine (DA) in the brain tissues were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total 74 components in HAD-Oil were determined by GC/MS, and cyperenone (20.46%) and α-cyperone (10.39%) had the highest relative content. The characterization results of the physical phase showed that volatile oils were successfully encapsulated by ß-cyclodextrin and HAD-OIC was produced. The average encapsulation rates of cyperenone and α-cyperone were 79.93% and 71.96%, respectively. The results of pharmacology study showed that all the test groups increased the body weight and decreased voluntary activity when compared with the model group (P < 0.05). The HAD-AE, HAD-OIC, and AE-OIC groups increased the levels of 5-HT in the sera and DA and Glu/γ-GABA in the brains, and AE-OIC groups showed better performance than the other test groups. CONCLUSIONS: HAD-Oil exerts sedative and hypnotic effects, which are increased when it is used with HAD-AEs. This result provides a favorable experimental evidence that volatile oils should be retained for the further development of HAD.

Green Production of a High-value Mosquito Insecticide of Nootkatone from Seaweed Hydrolysates.

Nootkatone is a type of valuable sesquiterpene that is widely used in food, cosmetics, fragrance, and other fields. The industry is faced with a major challenge due to the high expenses associated with plant-extracted nootkatone. We have developed a fermentation process for valencene production using seaweed hydrolysate as a carbon source via engineered Saccharomyces cerevisiae. Reduced-pressure distillation purified valencene was used as a substrate, and a yeast strain carrying HPO/AtCPR1 and ADH genes was constructed for whole-cell catalysis. After biotransformation at 25 °C for 3 h, a high yield of 73% for nootkatone production was obtained. Further, simple rotary evaporation was used to obtain nootkatone with a high purity of 97.4%. Mosquito-repellent testing showed that 1% nootkatone has a mosquito-repellent effect lasting up to 6 h, which is comparable to the 20% N,N-diethyl-meta-toluamide (DEET) effect. This study provided practical experience for developing third-generation biomass resources, generating new ideas for green manufacturing of valuable chemical products, and serving as a reference for creating efficient and eco-friendly mosquito repellents.

High Diversity of Epicoccum Associated with Leaf Spot on Italian Ryegrass in Southwestern China: Three New Species and Six New Records.

Italian ryegrass is widely cultivated for the productions of forage, hay and silage, due to its high nutritional value and good palatability. Leaf spots caused by fungi pose a serious threat to forage crops. In order to expand knowledge of fungi causing leaf spot in ryegrass (Lolium multiforum) in Sichuan, Yunnan, Chongqing and Guizhou of southwestern China, a comprehensive survey was undertaken from 2015 to 2022. Survey discovered that Epicoccum leaf spot (ELS) was a common and widespread disease, more serious at the late stage of growth (after late May); symptomatic leaf samples collected from the four different provinces were analyzed, and a total of 202 Epicoccum isolates were obtained; based on both multilocus phylogeny (ITS, LSU, TUB2, and RPB2) and morphology, 10 Epicoccum species were finally identified, including three novel species (E. endololii sp. nov., E. lolii sp. nov. and E. loliicola sp. nov.), six new host records (E. draconis, E. endophyticum, E. oryzae, E. plurivorum, E. thailandicum and E. tobaicum), and an unknown species (Epicoccum sp.1). Pathogenicity tests showed that E. endophyticum, E. endololii and Epicoccum sp.1 were non-pathogenic to Italian ryegrass, which were confirmed as endophytes in this study; other six species could infect Italian ryegrass and cause leaf lesions to different degrees, of which E. draconis was more aggressive (P ≤ 0.05). Coupling with the isolation rates and geographical distributions of these species, E. plurivorum was the predominant pathogen in Yunnan while E. oryzae and E. tobaicum in other three provinces. This work provides an initial understanding of the taxonomies, virulence and distributions of Epicoccum species associated with ELS of southwestern China, and lays a solid foundation for the diagnosis in the field, and scientific control of ELS on Italian ryegrass.

Pregnancy Outcomes in Patients with Primary Sjögren's Syndrome Undergoing Assisted Reproductive Therapy: A Multi-center Retrospective Study.

INTRODUCTION: The aim of this work was to investigate the pregnancy outcomes in infertile patients with primary Sjögren's syndrome (pSS) undergoing assisted reproductive therapy (ART). METHODS: A multi-center retrospective study was performed in pregnant women with pSS and ART from five tertiary hospitals from Guangdong Province from 2013 to 2022. Natural planned pregnancy in pSS and healthy people undergoing ART were selected as controls. Pregnancy outcomes were collected from medical records and compared among groups. RESULTS: Twenty-four pregnancies in pSS with ART, 70 natural planned pregnancies in pSS, and 96 pregnancies in healthy people with ART were analyzed. More than half of the pSS mothers undergoing ART have a past history of adverse pregnancy and spontaneous abortion was the most common (10/24, 41.7%). Primary infertility (25.0%) and recurrent spontaneous abortion (16.7%) were the leading causes of infertility in pSS. The major maternal adverse pregnancy outcome (APO) in pSS patients with ART was premature delivery (11/24, 45.8%), likely attributed to twin gestation (4/11, 36.4%) and fetal distress (3/11, 27.3%). Twenty-seven live infants were born from 22 successful deliveries. The live birth rate was 93.1% (27/29). The average delivery time was 36.1 ± 3.3 weeks of gestation. The average birthweight was 2434.4 ± 722.1 g, compared with 2844.9 g in natural planned pregnancy in pSS, and 3072.1 g from healthy mothers with ART (P < 0.001). Seven (25.9%) low-birthweight (LBW) infants were born, and the incidence was comparable to the other two groups (22.2% in natural pregnancy, 13.0% in healthy people, P = 0.09). No infants developed congenital heart block (CHB). CONCLUSIONS: ART is an effective method for infertility in patients with pSS. Premature delivery is the leading maternal APOs. The incidence of fetal APOs does not increase, while birthweight is lower in offspring from pSS mothers with ART.

Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and antitumor immunity through eNOS/Src.

Endothelial phospholipase Cγ (PLCγ) is essential for vascular development; however, its role in healthy, mature, or pathological vessels is unexplored. Here, we show that PLCγ was prominently expressed in vessels of several human cancer forms, notably in renal cell carcinoma (RCC). High PLCγ expression in clear cell RCC correlated with angiogenic activity and poor prognosis, while low expression correlated with immune cell activation. PLCγ was induced downstream of vascular endothelial growth factor receptor 2 (VEGFR2) phosphosite Y1173 (pY1173). Heterozygous Vegfr2Y1173F/+ mice or mice lacking endothelial PLCγ (Plcg1iECKO) exhibited a stabilized endothelial barrier and diminished vascular leakage. Barrier stabilization was accompanied by decreased expression of immunosuppressive cytokines, reduced infiltration of B cells, helper T cells and regulatory T cells, and improved response to chemo- and immunotherapy. Mechanistically, pY1173/PLCγ signaling induced Ca2+/protein kinase C-dependent activation of endothelial nitric oxide synthase (eNOS), required for tyrosine nitration and activation of Src. Src-induced phosphorylation of VE-cadherin at Y685 was accompanied by disintegration of endothelial junctions. This pY1173/PLCγ/eNOS/Src pathway was detected in both healthy and tumor vessels in Vegfr2Y1173F/+ mice, which displayed decreased activation of PLCγ and eNOS and suppressed vascular leakage. Thus, we believe that we have identified a clinically relevant endothelial PLCγ pathway downstream of VEGFR2 pY1173, which destabilizes the endothelial barrier and results in loss of antitumor immunity.

Recent Progress in Lithium-Ion Battery Safety Monitoring Based on Fiber Bragg Grating Sensors.

Lithium-ion batteries are widely used in a variety of fields due to their high energy density, high power density, long service life, and environmental friendliness. However, safety accidents with lithium-ion batteries occur frequently. The real-time safety monitoring of lithium-ion batteries is particularly important during their use. The fiber Bragg grating (FBG) sensors have some additional advantages over conventional electrochemical sensors, such as low invasiveness, electromagnetic anti-interference, and insulating properties. This paper reviews lithium-ion battery safety monitoring based on FBG sensors. The principles and sensing performance of FBG sensors are described. The single-parameter monitoring and dual-parameter monitoring of lithium-ion batteries based on FBG sensors are reviewed. The current application state of the monitored data in lithium-ion batteries is summarized. We also present a brief overview of the recent developments in FBG sensors used in lithium-ion batteries. Finally, we discuss future trends in lithium-ion battery safety monitoring based on FBG sensors.

Multi-omics reveals that green pea (Pisum sativum L.) hull supplementation ameliorates non-alcoholic fatty liver disease via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway.

Diets rich in various active ingredients may be an effective intervention strategy for non-alcoholic fatty liver disease (NAFLD). The green pea hull (GPH) is a processing by-product of green peas rich in dietary fiber and polyphenols. Here, a mouse model of NAFLD induced by DSS + high-fat diet (HFD) was established to explore the intervention effect of the GPH. The results showed that dietary supplements with the GPH can inhibit obesity and reduce lipid accumulation in the mouse liver to prevent liver fibrosis. GPH intervention can improve liver antioxidant capacity, reduce blood lipid deposition and maintain glucose homeostasis. DSS-induced disruption of the intestinal barrier aggravates NAFLD, which may be caused by the influx of large amounts of LPS. A multi-omics approach combining metabolomics and transcriptomic analysis indicated that glycine was the key target and its content was decreased in the liver after GPH intervention, and that dietary supplements with the GPH can relieve NAFLD via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway, which was further supported by liver-associated protein expression. In conclusion, our study demonstrated that dietary GPH can significantly ameliorate NAFLD, and the future development of related food products can enhance the economic value of the GPH.

Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.

BACKGROUND: Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood. METHODS: We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries. RESULTS: By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction. CONCLUSIONS: Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.

Auto-encoder design based on the 1D-VD-CNN model for the detection of honeysuckle from unknown origin.

The disadvantages of the traditional one-dimensional convolution neural network (1D-CNN) model based on honeysuckle near-infrared spectral data (NIRS) include high parameter quantity, low efficiency, and inability to identify unknown categories effectively. In this paper, we propose a one-dimensional very deep convolution neural network (1D-VD-CNN) and design an auto-encoder mechanism for detecting honeysuckle from unexplored habitats. First, the 1D-VD-CNN model uses the efficient very deep (VD) structure to replace the hidden layer structure in the traditional 1D-CNN model. The model can be directly applied to analyze one-dimensional near-infrared spectral data (NIRS). Second, combining the reconstruction error of the auto-encoder, a honeysuckle identification method considering an unknown origin is designed, which can solve the problem of high confidence in convolution neural networks by using an auto-encoder and reconstruction errors of the samples to be tested. Whether the sample is an unknown variety can be determined by comparing the corrected confidence level with the preset threshold value. The results show that the accuracy of the 1D-VD-CNN training set and test set is 100%, and the loss value converges to 0.001. Compared with the traditional 1D-CNN model, the parameters and FLOPs are reduced by nearly 71% and 8%, respectively. At the same time, compared with the NIRS analysis and the PLS-DA method, the 1D-VD-CNN model has higher efficiency and better recognition performance for honeysuckle near-infrared spectral classification. Meanwhile, the accuracy rate of the auto-encoder for the category detection mechanism of honeysuckle from an unknown origin is 98%. The model can quickly and efficiently classify honeysuckle from different habitats and detect honeysuckle from unexplored habitats.

Separation and structural characterization of unknown impurity in vancomycin by two-dimensional preparative liquid chromatography, LC-MS and NMR.

Vancomycin is an effective antibiotic used for the treatment of Gram-positive bacterial infections. During the analysis of vancomycin, an unknown impurity at the level of 0.5% was detected by high-performance liquid chromatography (HPLC). To characterize the structure of the impurity, a new two-dimensional preparative liquid chromatography (2D-Prep-LC) method was developed to separate the impurity from the vancomycin sample. After further analysis including liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the structure of the unknown impurity was identified as a vancomycin analog in which the N-Methyl-leucine residue on the side chain is replaced by an N-methylmethionine residue. In this study, we established a reliable and efficient method for separating and identifying vancomycin impurities, which will provide a valuable contribution to the field of pharmaceutical analysis and quality control.

Clinical Characteristics and Associated Factors for Infection and in-Hospital Mortality in Inpatients with Polymyositis/Dermatomyositis in China: A Retrospective Study.

Purpose: To investigate the clinical features of infection, and associated factor for in-hospital mortality in a southern Chinese cohort with polymyositis/dermatomyositis (PM/DM). Patients and Methods: Clinical data were retrospectively reviewed from 2015 to 2022 from a tertiary hospital in southern China. Associated factors for infection and in-hospital mortality were analyzed by multivariate logistic regression analysis. Results: A total of 554 patients with PM/DM were included, and 35.6% (197/554) of them developed 404 episodes of infection. Half of the patients developed infection within 4 months after disease onset. Bacterial infection was predominant (249/404, 61.6%). Lung was the most involved (242/404, 59.9%). Gram-negative bacteria the leading pathogens (64/84, 76.2%). Patients with anti-MDA5 positive were prone to develop severe infections (35.1% vs 16.4%, P<0.001) and had higher mortality (11.7% vs 3.4%, P=0.01). The in-hospital mortality was 6.5% (36/554). Infection was the leading cause of death (20/36, 55.6%). Older age (adjusted odds ratio (OR): 1.05, 95% confidential interval (CI): 1.02-1.09, P=0.004), ILD (adjusted OR: 2.76, 95% CI: 1.11-6.84, P=0.03), number of episodes of infection (adjusted OR: 1.91, 95% CI: 1.53-2.38, P<0.001), and elevated serum creatinine (Scr) (adjusted OR: 6.83, 95% CI: 1.77-26.40, P=0.01) were associated with in-hospital mortality. Conclusion: Infection is an early complication in PM/DM with a high proportion of lung involvement and predominance of gram-negative bacteria. It is a major contributor to in-hospital mortality. Older age, ILD, and number of episodes of infection are associated with poor prognosis.

Pregnancy outcomes in patients receiving assisted reproductive therapy with systemic lupus erythematosus: a multi-center retrospective study.

OBJECTIVES: To evaluate the safety, efficacy, and maternal and fetal outcomes of assisted reproductive therapy (ART) in systemic lupus erythematosus (SLE). METHODS: Patients from three tertiary hospitals from Guangzhou, China followed-up from 2013 to 2022 were included retrospectively. Patients with planned or unplanned natural pregnancy were chosen as controls. ART procedure and pregnancy outcomes were recorded and compared. RESULTS: A total of 322 ART cycles in 142 women were analyzed. Sixty-six intrauterine pregnancies out of 72 clinical pregnancies yielded 65 live infants, including 5 pairs of twins. The clinical pregnancy rate was 46.5% (66/142). The mean age at the first clinical pregnancy was 34.0 ± 3.8 years. The median (interquartile range, IQR) disease course was 42.5 (25, 84.8) months. Twenty-seven (40.9%) of them had a history of adverse pregnancy. Primary infertility occurred in 20 (30.3%) patients. Obstruction of fallopian tubes (17/66, 25.8%) and premature ovarian failure (9/66, 13.6%) were the leading causes for infertility. Ovulation induction therapy (OIT) were conducted in 60 (83.3%) pregnancies, and no ovarian hyperstimulation syndrome (OHSS) or thrombosis was observed. The leading maternal adverse pregnancy outcomes (APOs) included premature delivery (21/66, 31.8%), gestational diabetes mellitus (GDM) (15/66, 22.7%), and disease flares (10/66, 15.2%). Spontaneous premature delivery (9/21, 42.9%) and preterm premature rupture of membranes (PPROM) (6/21, 28.6%) were the leading causes for premature delivery. Preeclampsia (19.0% vs 0%, P = 0.012) increased in premature delivery. Infants delivered prematurely were likely to be low-birth-weight (LBW)/very-low-birth-weight (VLBW) (81.0% vs 7.7%, P < 0.001). Disease flares were mild (4/10, 40.0%) or moderate (5/10, 50.0%), and developed during the second (3/10, 30.0%) or third (6/10, 60.0%) trimester with favorable outcomes. Fetal loss in ART (6/66, 9.1%) was primarily attributed to early spontaneous abortion (n = 5). The average delivery time was 36.8 ± 2.1 weeks of gestation. The average birth weight was 2653.5 ± 578.6 g. LBW infants accounted for 30.8% (20/65). No neonatal death or neonatal lupus occurred. The incidence of adverse pregnancy outcomes did not increase in patients with ART compared with planned pregnancy and reduced significantly compared with an unplanned pregnancy. CONCLUSION: The safety and efficacy of ART is assured in lupus patients with stable disease. Maternal and fetal APOs are comparable with planned pregnancy, with a relatively high incidence of premature delivery, GDM, and LBW infants.

Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis.

OBJECTIVE: The aim of this study was to identify the role of Piezo1-mediated mechanotransduction in entheseal pathological new bone formation and to explore the underlying molecular mechanism. METHODS: Spinal ligament tissues were collected from 14 patients with ankylosing spondylitis (AS) and 14 non-AS controls and bulk RNA sequencing was conducted. Collagen antibody-induced arthritis models were established to observe pathological new bone formation. Pharmacological inhibition and genetic ablation of Piezo1 was performed in animal models to identify the essential role of Piezo1. Entheseal osteo-chondral lineage cells were collected and in vitro cell culture system was established to study the role and underlying mechanism of Piezo1 in regulation of chondrogenesis, osteogenesis and its own expression. RESULTS: Piezo1 was aberrantly upregulated in ligaments and entheseal tissues from patients with AS and animal models. Pharmaceutical and genetic inhibition of Piezo1 attenuated while activation of Piezo1 promoted pathological new bone formation. Mechanistically, activation of CaMKII (Calcium/calmodulin dependent protein kinase II) signalling was found essential for Piezo1-mediated mechanotransduction. In addition, Piezo1 was upregulated by AS-associated inflammatory cytokines. CONCLUSION: Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation through CaMKII signalling in AS.

Neoadjuvant Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is characterized by low resection and high postoperative recurrence rates, and conventional treatment strategies have failed to meet clinical needs. Neoadjuvant therapy (NAT) is widely employed in the routine management of several solid tumors because it increases resectability and reduces the rate of postoperative recurrence. However, a consensus has not been reached regarding the effects of NAT on HCC. As systemic therapy, particularly targeted therapy and immunotherapy, is given for HCC treatment, accumulating evidence shows that the "spring" of NAT for HCC is imminent. In the future, HCC researchers should focus on identifying biomarkers for treatment response, explore the mechanisms of resistance, and standardize the endpoints of NAT.

Investigation of atropisomeric transformation of a novel PDE4 inhibitor with tetrahydroisoquinoline-based amide group and its primary study of binding to HSA.

In this study a kinetic and thermodynamic atropisomeric transformation due to a hindered rotation around the tetrahydroisoquinoline-based amide group was investigated. Quantum chemistry calculations were applied to investigate the transformation under the gas phase and several solvents with different polarity, and then evaluated by dynamic HPLC determination. It was found that the transformation rate of constants and the half-life time varied under the influence of solvent polarity and temperature and the energies of rotational barrier were determined ranging between 87 and 92 kJ∙mol-1. A primary binding study with HSA confirmed a rapid interconversion under the simulated physiological conditions. It is therefore suggested to take this atropisomeric compound as a racemic mixture for its future drug development.