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Zi-Yang Zhang,1 Lin-Xiao Huang,1 Zhi-Wei Xu,1 Peng Wang,1 Yun Lei,1,2 Ai-Lin Liu1,2 1Department of Pharmaceutical Analysis, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of ChinaCorrespondence: Yun Lei; Ai-Lin LiuDepartment of Pharmaceutical Analysis, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of ChinaTel +86 591 22862016Email lypiglet@163.com; ailinliu@fjmu.edu.cnPurpose: The PML/RARα fusion gene as a leukemogenesis plays a significant role in clinical diagnosis of the early stage of acute promyelocytic leukemia (APL). Here, we present an electrochemical biosensor for PML/RARα fusion gene detection using carbon dots functionalized graphene oxide (CDs/GO) nanocomposites modified glassy carbon electrode (CDs/GO/GCE).Materials and Methods: In this work, the CDs/GO nanocomposites are produced through π-π stacking interaction and could be prepared in large quantities by a facile and economical way. The CDs/GO nanocomposites were decorated onto electrode surface to improve the electrochemical activity and as a bio-platform attracted the target deoxyribonucleic acid (DNA) probe simultaneously.Results: The CDs/GO/GCE was fabricated successfully and exhibits high electrochemical activity, good biocompatibility, and strong bioaffinity toward the target DNA sequences, compared with only the pristine CDs on GCE or GO on GCE. The DNA biosensor displays excellent sensing performance for detecting the relevant pathogenic DNA of APL with a detection limit of 83 pM (S/N = 3).Conclusion: According to the several experimental results, we believe that the simple and economical DNA biosensor has the potential to be an effective and powerful tool for detection of pathogenic genes in the clinical diagnosis.Keywords: acute promyelocytic leukemia, pathogenic genes, electrochemical biosensor, ex-situ method, carbon nanomaterials

Evaluating the anodized tantalum pentoxide (Ta2O5) that has been recently reported as a dielectric for low-voltage electrowetting-on-dielectric (EWOD) devices, we find a severe deterioration in performance if the working liquid is actuated with positive dc voltage. In an effort to reduce the limitation of this otherwise attractive dielectric material for EWOD, proposed herein is a Ta2O5 layer prepared by anodizing a sputtered Ta2O5 film. This sputtered-anodized Ta2O5 allows the use of positive dc signals, while maintaining the low-voltage actuation for which the anodized Ta 2O5 was originally introduced. All the EWOD tests were performed with a conductive liquid droplet in an air environment. © 1992-2012 IEEE.

This study aimed to fractionate and characterize the protein-rich polysaccharide-protein (PSP) complexes from a well-known edible mushroom, Lentinula edodes, and assess their nutritional and immunostimulatory properties. Crude PSP isolated from the mushroom water extract was purified by anion exchange chromatography, yielding fractions PSP-F1 and PSP-F2 containing 66.1 % and 74.0 % protein, respectively. Both fractions exhibited primarily β-sheet and random-coil protein structures, though the crude PSP fraction exhibited an additional α-helix structure. On SDS-PAGE, PSP-F1 showed two molecular weight bands, one below 10 kDa and another at 34 kDa, and PSP-F2 showed several bands, one below 10 kDa and others between 34 and 95 kDa. The nutritional value of essential and non-essential amino acid profiles was in the order of PSP-F2 > PSP-F1 > crude PSP; the amino acid ratio coefficient values of the crude PSP, PSP-F1, and PSP-F2 were 63 %, 67 %, and 72 %, respectively. The combination of PS and PSP fractions exhibited stronger immunoactivity than PSP-F1 or PSP-F2 alone. PSP-F2 showed a higher immunostimulatory activity than PSP-F1 in RAW264.7 cell culture. PSP-F2 was also more abundant of easily absorbed high-quality proteins. The results provide useful references for dietary and medicinal uses of PSP fractions in L. edodes and other edible mushrooms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian Yong WU reports was provided by The Hong Kong Polytechnic University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lentinula edodes (Shiitake) is an important edible mushroom and polysaccharides are its major constituents with proven health benefits. The study was to investigate the gut bacterial fermentation and subsequent effects on gut barrier function of a glucan-rich polysaccharide, LePS40 precipitated from the mushroom water extract with 40 % (v/v) ethanol. LePS40 consisted of a β-(1→3)-glucan main chain with substitution in the C-6 position with side chains mainly composed of (1 → 6)-linked β-Glcp residues, (1 → 6)-linked α-Galp residues and terminal residues of β-Glcp. LePS40 was found highly resistant to digestive enzymes and gastric acid in simulated human gastrointestinal tract, but highly fermentable during in vitro human fecal fermentation. The fecal fermentation degradation of LePS40 appeared to selectively break the glucoside linkage in view of the dramatic decrease in the glucose molar ratio (12.68 to 1.07). Compared with the prebiotic reference FOS, LePS40 led to much higher levels of butyric, and propionic acid and a lower level of acetic acid. Moreover, LePS40 enhanced the abundance of some beneficial bacterial populations, but decreased the bacteria possibly linked with fatty-liver disease and colorectal cancer. Furthermore, the fecal fermentation products of LePS40 showed a potential protective effect on intestinal barrier function against inflammatory damage in Caco-2/Raw264.7 co-culture model. These findings suggest the potential of LePS40 for improvement of gut health through modulation of gut microbiota., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multiple resonance (MR) boron-nitrogen doped polycyclic aromatic hydrocarbons (BN-PAHs) have shown compelling thermally activated delayed fluorescence (TADF), surpassing those of their hydrocarbon analogues. However, the structural variety of π-extended BN-PAHs remains narrow. In this study, we synthesized three double helical BN-doped nanographenes (BN-NGs), 2 a-2 c, and three heptagon-embedded BN-NGs, 1 a-1 c, by π-extension of the MR core. During the formation of 2 a, a nanographene with one heptagon (1 a) was obtained, whereas further dehydrocyclization of the [6]helicene units within 2 b and 2 c led to heptagon structures, yielding other two BN-NGs containing double heptagons (1 b and 1 c). These BN-NGs (2 a-2 c and 1 a-1 c) showed pronounced redshifts of 100-190 nm compared to the parent MR core, while preserving the TADF characteristics and prolonging the delayed fluorescence lifetime to the millisecond level. Furthermore, the integration of a heptagon ring into 1 a-1 c expanded the conjugation, reduced the oxidation potentials, and yielded a more flexible framework compared to those of 2 a-2 c. The enantiomers of 2 a-2 c, 1 a, and 1 c were resolved and their chiroptical properties were studied. Notably, 1 a and 1 c exhibited increased chiroptical dissymmetry factors., (© 2024 Wiley-VCH GmbH.)

Peripheral nerve injury (PNI) can result in severe disabilities, profoundly impacting patients' quality of life and potentially endangering their lives. Therefore, understanding the potential molecular mechanisms that facilitate the regeneration of damaged nerves is crucial. Evidence indicates that Schwann cells (SCs) play a pivotal role in repairing peripheral nerve injuries. Previous studies have shown that RNA, particularly non-coding RNA (ncRNA), plays a crucial role in nerve regeneration, including the proliferation and dedifferentiation of SCs. In this review, the individual roles of ncRNA in SCs and PNI are analyzed. This review not only enhances the understanding of ncRNA's role in nerve injury repair but also provides a significant theoretical foundation and inspiration for the development of new therapeutic strategies., (© 2024 Wiley‐VCH GmbH.)

Background: Low-density neutrophils are heterogeneous immune cells with immunosuppressive (such as polymorphonuclear myeloid-derived suppressor cells [PMN-MDSC]) or pro-inflammatory (such as low-density granulocytes [LDG]) properties that have been well described in multiple cancers and immune diseases. However, its role in allergic rhinitis (AR) is still unclear., Methods: In the present study, we defined low-density neutrophils as CD14 - CD11B + CD15 + LOX-1 + (LOX-1 + neutrophils), and their levels in the peripheral blood (PB) were evaluated and compared between patients with AR and healthy donors using flow cytometric analysis. LOX-1 expression on polymorphonuclear neutrophils was identified. Carboxyfluorescein succinimidyl ester (CFSE)-stained CD3 + T cells were cultured alone or with LOX-1 + neutrophils, T cell proliferation was assessed using flow cytometry, and pro-inflammatory cytokines in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). Clinicopathological analyses were performed to gain a thorough understanding of LOX-1 + neutrophils., Results: We determined that LOX-1 + neutrophils were significantly increased in the PB of patients with AR, and LOX-1 expression in neutrophils from patients with AR was elevated. Interestingly, LOX-1 + neutrophils derived from patients with AR, unlike PMN-MDSC, promoted T cell proliferation and pro-inflammatory cytokine production. Moreover, clinicopathological analysis revealed that there was no any relation between circulating LOX-1 + neutrophil levels and the levels of IgE, age and sex., Conclusion: These findings indicate that elevated circulating LOX-1 + neutrophils play a pro-inflammatory role in AR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs., Competing Interests: BF have been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2023. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation., (© 2024. The Author(s).)

Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4 + T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs., (© 2024 Wiley-VCH GmbH.)

Ischemic stroke is a significant burden on human health worldwide. Carotid Atherosclerosis stenosis plays an important role in the comprehensive assessment and prevention of ischemic stroke patients. High-resolution vessel wall magnetic resonance imaging has emerged as a successful technique for assessing carotid atherosclerosis stenosis. This advanced imaging modality has shown promise in effectively displaying a wide range of characteristics associated with the condition, leading to a comprehensive evaluation. High-resolution vessel wall magnetic resonance imaging not only enables a comprehensive evaluation of the instability of carotid atherosclerosis stenosis plaques but also provides valuable information for understanding the pathogenesis and predicting the prognosis of ischemic stroke patients. The purpose of this article is to review the application of high-resolution magnetic resonance imaging in ischemic stroke and carotid atherosclerotic stenosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: To evaluate the value of implementing a modified reverse puncture procedure for esophagojejunostomy during totally laparoscopic total gastrectomy. Methods: This was a descriptive case series. Relevant clinical data, including the operative procedure, recovery, and pathological findings of 35 patients with gastric cancer who had undergone esophagojejunostomy with a modified reverse puncture technique during totally laparoscopic total gastrectomy in the Department of Gastrointestinal Surgery, Fujian Provincial Hospital, from June 2022 to January 2023, were prospectively collected and retrospectively analyzed. The age of all patients in the group was (64.9±8.0) years old, with 22 males (62.9%) and a body mass index of (23.2±2.4) kg/m 2 . The tumors were located in the upper and middle parts of the stomach in 24 cases (68.6%) and in the junction of the esophagus and stomach in 11 cases (31.4%). Important technical aspects of the modified reverse puncture procedure are as follows. (1) Site of the esophageal incision: a transverse incision is made across the right lateral wall of the esophagus at the expected site of esophageal disjunction. (2) Technique for inserting an anvil: after threading a silk thread through the tip of anvil, the end of the thread is knotted and fixed as the traction thread, after which an anvil is inserted into the esophagus through the esophageal incision, leaving the end of the traction line exposed. Next, a 60-mm linear cutter is placed through the right midclavicular trocar to straighten the opened esophagus vertically, after which the rod of the anvil is pulled out of a small incision that has been made in the esophagus by pulling the traction thread, thus completing anvil placement. (3) Jejunal binding: the jejunum on the central bar of the stapler is fastened with silk thread to the stump of the jejunum, and then tied to the output loop of the jejunum with a gauze strip. Results: All 35 surgeries were successful, with no mortality or conversion to laparotomy. The operation time, anvil insertion time, and digestive tract reconstruction time were (232.7±34.4), (8.5±1.4), and (40.5±4.8) minutes, respectively. The intraoperative blood loss was 100 (20-250) mL and the incision was (5.3±0.9) cm long. The upper surgical margin was negative in all patients and the mean distance between the upper and tumor margins was (3.5±1.2) cm. The mean number of lymph nodes dissected per patient was 33.9±7.1. The times to initial ambulation, initial passage of flatus , postoperative fluid intake, and length of postoperative hospital stay were (3.2±1.1), (3.7±1.5), (4.6±2.3), and (9.8±3.2) days, respectively. Postoperative complications occurred in five patients: one case of anastomotic leak, two of anastomotic stenosis, one of pulmonary infection, and one of incomplete intestinal obstruction, all of which were successfully managed conservatively. Conclusion: Esophagojejunostomy using a modified reverse puncture technique during totally laparoscopic total gastrectomy is safe and feasible for gastric cancer, requiring only a small incision and achieving higher upper esophageal resection margins and good postoperative recovery, and therefore warrants further implementation.

Since microRNAs (miRNAs) are predictors of tumorigenesis, accurate identification and quantification of miRNAs with highly similar sequences are expected to reflect tumor diagnosis and treatment. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor was constructed for miRNAs determination based on Y-shaped junction structure equipped with locked nucleic acids (LNA), graphene oxide-based nanocomposite to enrich luminophores, and conductive matrix. Specifically, two LNA-modified probes were designed for specific miRNA recognition, that is, a dual-amine functionalized hairpin capture probe and a signal probe. A Y-shaped DNA junction structure was generated on the electrode surface upon miRNA hybridizing across the two branches, so as to enhance the selectivity. Carbon quantum dots-polyethylene imine-graphene oxide (CQDs-PEI-GO) nanocomposites were developed to enrich luminophores CQDs, and thus enhancing the ECL intensity. For indirect signal amplification, an electrochemically activated poly(2-aminoterephthalic acid) (ATA) film decorated with gold nanoparticles was prepared on electrode as an effective matrix to accelerate the electron transfer. The fabricated ECL biosensor achieved sensitive determination of miRNA-222 with a limit-of-detection (LOD) as low as 1.95 fM (S/N = 3). Notably, Y-shaped junction structures equipped with LNA probes endowed ECL biosensor with salient single-base discrimination ability and anti-interference capacity. Overall, the proposed Y-shaped ECL biosensor has considerable promise for clinical biomarker determination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acupoint is the basis of acupuncture. To elaborate the theory of acupuncture, the structure and function of acupoint should be clarified in advance. By exploring the discussion upon the classification, distribution and structure of acupoint in Huangdi Neijing ( Inner Canon of Yellow Emperor ), qi zheng lun (on meridian points and extra points), jie jiao lun (on convergence of joints) and guan ji lun (on three-dimensional structure of acupoint) are extracted. Based on whether located on the fixed sites, acupoints are classified into meridian points and extra points, while the meridian points are divided into 4 categories, i.e maishu , gukong , qixue and muxue . The convergence of joints illustrates the principal rule of acupoint distribution. The density of the major and key acupoints is proportional to the size and the complexity of function of joints. Acupoint is recognized as a three-dimensional structure in consideration of its external distribution on the body surface and the substances inside the body, which can be explored and examined. In addition, the relationship between meridian points and extra points, the significance of meridian points in different conditions, and the approaches to acupoint study are deeply discussed and analyzed. The crucial problems and the way for solving them are proposed for the future study to provide the references to the inheritance and innovation of acupuncture.

Objective: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs)., Patients and Methods: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed., Results: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001)., Conclusions: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

Background and Purpose: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study combined HR-VWI, hemodynamics, and peripheral blood inflammatory indicators to investigate the role of these factors in symptomatic intracranial atherosclerotic stenosis (sICAS) and their inter-relationships., Methods: Patients diagnosed with atherosclerotic middle cerebral artery stenosis were recruited retrospectively from June 2018 to July 2022. Plaque enhancement was qualitatively and quantitatively analyzed, and the degree of plaque enhancement was graded according to the plaque-to-pituitary stalk contrast ratio (CR). Computational fluid dynamics models were constructed, and then hemodynamic parameters, including wall shear stress (WSS) and pressure ratio (PR), were measured and recorded. Univariate and multivariable analyses were performed to identify factors that can predict sICAS. In addition, the correlation analysis between the plaque characteristics on HR-VWI, hemodynamic parameters, and peripheral blood inflammatory indicators was performed to investigate the interrelationships between these factors., Results: Thirty-two patients were included. A higher proportion of plaque enhancement, maximum WSS, and WSS ratio (WSSR) were significantly associated with sICAS. The multiple logistic regression analysis showed that only the WSSR was an independent risk factor for sICAS. The correlation analysis revealed that both the CR and plaque burden showed linear positive correlation with the WSSR (R = 0.411, P = 0.022; R = 0.474, P = 0.007, respectively), and showed linear negative correlation with the lymphocyte to monocyte ratio (R = 0.382, P = 0.031; R = 0.716, P < 0.001, respectively)., Conclusions: The plaque enhancement and WSSR were significantly associated with sICAS, WSSR was an independent risk factor for sICAS. Plaque enhancement and plaque burden showed linear correlation with the WSSR and lymphocyte-to-monocyte ratio (LMR). Hemodynamics and inflammation combined to promote plaque progression., (© 2023. The Author(s).)

Wurfbainia longiligularis and Wurfbainia villosa are both rich in volatile terpenoids and are 2 primary plant sources of Fructus Amomi used for curing gastrointestinal diseases. Metabolomic profiling has demonstrated that bornyl diphosphate (BPP)-related terpenoids are more abundant in the W. villosa seeds and have a wider tissue distribution in W. longiligularis. To explore the genetic mechanisms underlying the volatile terpenoid divergence, a high-quality chromosome-level genome of W. longiligularis (2.29 Gb, contig N50 of 80.39 Mb) was assembled. Functional characterization of 17 terpene synthases (WlTPSs) revealed that WlBPPS, along with WlTPS 24/26/28 with bornyl diphosphate synthase (BPPS) activity, contributes to the wider tissue distribution of BPP-related terpenoids in W. longiligularis compared to W. villosa. Furthermore, transgenic Nicotiana tabacum showed that the GCN4-motif element positively regulates seed expression of WvBPPS and thus promotes the enrichment of BPP-related terpenoids in W. villosa seeds. Systematic identification and analysis of candidate TPS in 29 monocot plants from 16 families indicated that substantial expansion of TPS-a and TPS-b subfamily genes in Zingiberaceae may have driven increased diversity and production of volatile terpenoids. Evolutionary analysis and functional identification of BPPS genes showed that BPP-related terpenoids may be distributed only in the Zingiberaceae of monocot plants. This research provides valuable genomic resources for breeding and improving Fructus Amomi with medicinal and edible value and sheds light on the evolution of terpenoid biosynthesis in Zingiberaceae., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cellulose, as a component of green plants, becomes attractive for fabricating biocompatible flexible functional devices but is plagued by hydrophilic properties, which make it easily break down in water by poor mechanical stability. Here we report a class of SiO 2 -nanoparticle-decorated bacteria-cellulose meta-skin with superior stability in water, excellent machining property, ultrathin thickness, and active bacteria-repairing capacity. We further develop functional ultrasonic metasurfaces based on meta-skin paper-cutting that can generate intricate patterns of ~10 μm precision. Benefited from the perfect ultrasound insulation of surface Cassie-Baxter states, we utilize meta-skin paper-cutting to design and fabricate ultrathin (~20 μm) and super-light (<20 mg) chip-scale devices, such as nonlocal holographic meta-lens and the 3D imaging meta-lens, realizing complicated acoustic holograms and high-resolution 3D ultrasound imaging in far fields. The decorated bacteria-cellulose ultrasonic metasurface opens the way for exploiting flexible and biologically degradable metamaterial devices with functionality customization and key applications in advanced biomedical engineering technologies., (© 2023. Springer Nature Limited.)

Aim: To evaluate the potential of two trabecular meshwork (TM)-specific promoters, Chitinase 3-like 1 (Ch3L1) and matrix gla protein (MGP), for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2 (scAAV2) vector technologies., Methods: An scAAV2 vector with C3 transferase (C3) as the reporter gene (scAAV2-C3) was selected. The scAAV2-C3 vectors were driven by Ch3L1 (scAAV2-Ch3L1-C3), MGP (scAAV2-MGP-C3), enhanced MGP (scAAV2-eMGP-C3) and cytomegalovirus (scAAV2-CMV-C3), respectively. The cultured primary human TM cells were treated with each vector at different multiplicities of infections. Changes in cell morphology were observed by phase contrast microscopy. Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining, real-time quantitative polymerase chain reaction and Western blot. Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively. In vivo green fluorescence was visualized by a Micron III Retinal Imaging Microscope. Intraocular pressure (IOP) was monitored using a rebound tonometer. Ocular responses were evaluated by slit-lamp microscopy. Ocular histopathology analysis was examined by hematoxylin and eosin staining., Results: In TM cell culture studies, the vector-mediated C3 expression induced morphologic changes, disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rho-associated protein kinase signaling pathway. At the same dose, these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3, but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3. At low-injected dose, the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGP-C3-injected and scAAV2-eMGP-C3-injected eyes. At high-injected dose, significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes. Similar to scAAV2-CMV-C3, scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium. In anterior segment tissues of scAAV2-eMGP-C3-injected eyes, no obvious morphological changes were found except for the TM. Inflammation was absent., Conclusion: In scAAV2-transduced TM cells, the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus, but obviously higher than that of MGP. In the anterior chamber of rat eye, the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter, but not by Ch3L1 promoter. These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector., (International Journal of Ophthalmology Press.)

It has the important enlightenment and reference significance for the inheritance and innovation of jin (sinew/fascia) diseases and its theoretic basis, jingjin (muscle region of meridian) doctrine by sorting out the origin of the acupuncture techniques for jin diseases and exploring the root of its rise and fall. Using context analysis, overall investigation and practice test, the paper elaborates the basic concepts, e.g. needling techniques for jin , jingjin , jinji (muscular contracture) and jiejin (knotted tendon), and jingjin doctrine. In particular, the three key concepts, i.e. fanzhen jieci (heating after needling), yizhi weishu (feelings from patients and acupuncture operators) and yitong weishu (the worst painful sites of muscle spasm) are deeply investigated. These three concepts, involved in the treatment of jingjin disorders, treatment principles and methods, are of a great controversy in the current academic circle. The author clarified the category of needling for jin disease and main needling techniques, investigated specially the origin of fanzhen jieci and guancifa (repeated needling directly on the foci), and explored the evolution of the needling methods that had been controversial or neglected for a long time, i.e. neire cifa (technique for inducing heat inside for cold obstruction), guancifa , tiaocifa (inserting the needles around the foci), fencifa (intramuscular needling) and mucifa (deep puncturing to the peritoneum or on front- mu points). Finally, from the relationship between jin and mai (meridian), and the differences between dry needling and acupuncture technique for jin diseases, the author explored the crucial problems and countermeasures urgently required in the future development of jingjin doctrine so as to provide the references for the theoretical innovation of acupuncture- moxibustion science.

Objective: To improve the awareness of hemophagocytic syndrome(HPS) secondary to COVID-19 (COVID-sHPS). Methods: We reported an adult case of COVID-sHPS, including clinical presentation, laboratory examinations, histopathological findings, treatment strategy, and outcome. We also conducted literature research in PubMed database and Wanfang database using the keywords "COVID-19" and "hemophagocytic syndrome" and subsequently summarized relevant literature. Results: A 49-year-old man was admitted to our hospital after 4 weeks of recurrent fever. Prior to this hospitalization, he had received an empiric combination therapy with antibiotics and antiviral drugs against SARS-CoV-2. His vital signs were within the normal range and no abnormalities were found on physical examination on admission. After admission, throat swab nucleic acid tests were weakly positive for SARS-CoV-2, and negative for influenza and respiratory syncytial virus. Blood nucleic acid tests for cytomegalovirus and EB virus were negative, as was blood mNGS. Laboratory tests showed a series of abnormalities, including leukopenia, thrombocytopenia, low fibrinogen, elevated serum ferritin, elevated transaminase, decreased NK cell activity, and hemophagocytosis in bone marrow. According to the HPS-2004 diagnostic criteria, he was diagnosed with hemophagocytic syndrome, which was high likely to be caused by COVID-19 infection due to the lack of evidence of genetic risk factors and other clear triggers. He was initially treated with dexamethasone at a dose of 10 mg·m -2 ·d -1 and his condition improved rapidly. The literature search identified twenty-three articles on COVID-sHPS, 22 of which were in English. A total of 89 patients had COVID-sHPS and 55 (61.7%) were male. COVID-sHPS could occur at any age, but mainly in adults (86/89, 96%). Fever was reported in the literature with a clear description of the course of the disease. Most HPS occurred during the acute phase of COVID-19, but 3 patients developed HPS during the convalescent phase. Almost all reported cases presented with increased ferritin, elevated transaminases, elevated triglycerides, and cytopenia, mainly anemia and thrombocytopenia. In the retrieved literature, HS-score≥169 was frequently used to diagnose COVID-sHPS, and glucocorticoid in combination with immunoglobulin was the most common treatment strategy. COVID-sHPS had a poor prognosis and a high mortality rate (84.2%, 75/89). Conclusions: The prognosis of COVID-sHPS is poor, so clinicians should raise their awareness of the disease, identify high-risk suspected populations, and arrange reasonable relevant examinations for definite diagnosis and early initial treatment to improve their outcome.

Background: Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs., Methods: Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems., Results: sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs., Conclusions: We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation., (© 2023. The Author(s).)

Sample pretreatment technology plays a vital role in the analysis of complex samples and is key to the entire analytical process. Its main purpose is to separate the substance to be measured from the sample matrix or interfering substances in the sample and to achieve a state in which the instrument can be analyzed and detected. Traditional sample pretreatment techniques include liquid-liquid extraction, liquid-solid extraction, precipitation separation, solvent volatilization-rotary evaporation, filtration, and centrifugation. However, the applications of these methods are limited by their low extraction efficiency, complicated operation, long time consumption, unstable recovery, use of large amounts of organic solvents, and large error rates. Several new sample pretreatment techniques, including solid-phase extraction, magnetic solid-phase extraction, solid-phase microextraction, and dispersive solid-phase extraction, have been developed and rapidly applied to various fields to overcome the shortcomings of traditional sample pretreatment methods. However, the development of adsorbent materials with high selectivity and enrichment capability remains a challenge in sample pretreatment technology, in which adsorbents with excellent adsorption performance are crucial. In recent years, various nanomaterials with remarkable properties have been introduced and applied to sample pretreatment, and numerous nano-extraction materials with diverse functions and high selectivity and enrichment capability have been developed. Hollow nanomaterials are nanoparticles with large voids in their solid shells. Owing to their advantageous properties, which include a large effective surface area, abundant internal space, low density, variety of preparation methods, structural and functional tailorability, short mass transmission path, and high carrying capacity, hollow nanomaterials show great application potential in sample pretreatment. The extraction mechanism of these materials is based on the synergistic effects of π-π stacking, electrostatic, hydrogen-bonding, and hydrophobic interactions to achieve the efficient separation and enrichment of the target analytes. Given their noteworthy physicochemical properties, hollow nanomaterials have gained wide attention in various research fields and are considered a research frontier in the field of materials science. Changing the structure or surface properties of the core and shell can lead to various hollow nanomaterials with unique properties. Such changes can create synergy between the physicochemical properties and structural function of the original core-shell material, leading to novel materials with superior performance compared with the starting materials and broad application prospects in sample pretreatment. Nevertheless, only a few hollow nanomaterials with diverse structures and functions are currently used for sample pretreatment, and their adsorption capacity for target analytes is often unsatisfactory. Consequently, enhancing the adsorption selectivity of these materials toward various analytes is the most important step in sample pretreatment. First, hollow nanomaterials with a large specific surface area and suitable pore size can be designed to achieve the specific adsorption of target analytes of varying sizes. The combination of hollow nanomaterials with other materials presenting desirable adsorption properties could also lead to synergistic effects and enhance the performance of composite hollow nanomaterials. In addition, more green methods to prepare hollow nanomaterials with outstanding selectivity can be explored to achieve the superior adsorption of a specific target analyte. Efforts to synthesize hollow nanomaterials have been met with great success, but the available synthesis methods still suffer from complicated steps, high costs, relatively harsh conditions, and the use of highly toxic substances. This paper summarizes the main types of hollow nanomaterials, their synthesis methods, and research progress on sample pretreatment technologies (solid-phase extraction, solid-phase microextraction, magnetic solid-phase extraction, and dispersive solid-phase extraction) and describes the challenges encountered in the synthesis of hollow nanomaterials. The applications and developments of hollow nanomaterials in sample pretreatment are also discussed.

Objective: This study aimed at comparing sacrospinous ligament fixation (SSLF) with uterosacral and cardinal ligament fixation (USCLF) concerning complications and outcomes in patients with pelvic organ prolapse (POP)., Methods: A retrospective analysis was performed on the clinical data of patients with POP stage III or above uterine prolapse treated at Wenzhou People's Hospital from January 2013 to December 2019. Patients were divided into two groups: USCLF group and SSLF group. The perioperative indicators, postoperative complications, pelvic organ prolapse quantification (POP-Q), Pelvic Floor Distress Inventory-20 (PFDI-20), and POP/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) scores of the groups were analyzed and compared., Results: (1) The operative time and intraoperative blood loss in the USCLF group were lower than those in the SSLF group, with statistical significance ( p < 0.05). (2) The incidence of postoperative buttock pain in the SSLF group was 10.7% (6/56), higher than that in the USCLF group (0/56) (Fisher's exact test, p = 0.027). (3) At one year of follow-up, significant improvement in Aa, Ba, C, Ap, and Bp values was observed in both groups ( p < 0.05). The values of the Aa and Ba sites in the USCLF group were lower than those in the SSLF group one year after surgery ( p < 0.05). (4) The PFDI-20 and PISQ-12 scores of the groups one year after surgery were lower than those before surgery ( p < 0.05)., Conclusion: Uterosacral and cardinal ligament suture fixation leads to less bleeding and better postoperative quality of life than preoperative and may be better than SSLF at preventing the recurrence of anterior wall prolapse after surgery., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Ling-xiao Huang et al.)

Background and Purpose: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke (IS), and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study aimed to qualitatively and quantitatively assess plaque enhancement of ICAS and to investigate the relationship between plaque enhancement, plaque morphological features, and IS., Methods: Data from adult patients with ICAS from April 2018 to July 2022 were retrospectively collected, and all patients underwent HR-VWI examination. Plaque enhancement was qualitatively and quantitatively assessed, and the plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Plaque characteristics, such as plaque burden and area, were quantitatively measured using HR-VWI. Furthermore, receiver-operating characteristic (ROC) analysis was performed to assess the ability of CR to discriminate plaque enhancement. The patients were divided into a symptomatic ICAS group and an asymptomatic ICAS group according to the clinical and imaging characteristics. Univariate and multivariate analyses were performed to investigate which factors were significantly associated with plaque enhancement and symptomatic ICAS. The plaque burden and CR were compared using linear regression., Results: A total of 91 patients with ICAS were enrolled in this study. ICAS plaque burden was significantly associated with plaque enhancement (p = .037), and plaque burden was linearly positively correlated with CR (R = 0.357, p = .001). ROC analysis showed that the cutoff value of CR for plaque enhancement was 0.56 (specificity of 81.8%). Both plaque enhancement and plaque burden were significantly associated with symptomatic ICAS, and only plaque enhancement was an independent risk factor after multivariate analysis., Conclusion: Plaque burden was an independent risk factor for plaque enhancement and showed a linear positive correlation with CR. The cutoff value of CR for plaque enhancement was 0.56, and CR ≥ 0.56 was significantly associated with symptomatic ICAS, which was independently associated with plaque enhancement., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

In the era of antiviral therapy, the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus (HBV) replication to the pursuit of serological clearance of HBs surface antigen (HBsAg). Based on the life cycle of HBV, HBsAg originates from covalently closed circular DNA (cccDNA) and integrated HBV DNA, thus reflecting their transcriptional activity. Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA. HBsAg loss improves the recovery of abnormal immune function, which in turn, may further promote the clearance of residual viruses. Combined with functional cure and the great improvement of clinical outcomes, the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B (CHB). For many other risk factors besides HBV itself, patients with HBsAg loss still need regular monitoring. In this review, we summarized the evolution of CHB treatment, the origin of serum HBsAg, the pattern of HBsAg seroclearance, and the effect of HBsAg loss on immune function and disease outcomes. In addition, we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Wurfbainia villosa fruit is rich in volatile terpenoids, among which pinene is one of the main components and has anti-inflammatory, antibacterial, anti-tumor, and other pharmacological activities. This research group found that W. villosa fruits were rich in α-pinene by GC-MS, and terpene synthase(WvTPS63, formerly known as AvTPS1) with β-pinene as the main product was cloned and identified, but α-pinene synthase had not been identified. In this study, based on the genome data of W. villosa, we screened and found WvTPS66 with highly similar sequences to WvTPS63, identified enzyme functions of WvTPS66 in vitro, and performed a comparative analysis of sequence, catalytic function, expression pattern, and promoter with WvTPS63. Multiple sequence alignment showed that the amino acid sequences of WvTPS63 and WvTPS66 were highly similar and the conservative motif of terpene synthase was almost identical. In vitro enzymatic experiments on catalytic functions showed that both could produce pinene, and the main product of WvTPS63 was β-pinene, while that of WvTPS66 was α-pinene. Expression pattern analysis showed that WvTS63 was highly expressed in flowers, WvTPS66 was expressed in the whole plant, and the highest expression level was found in the pericarp, which indicated that it might be mainly responsible for the synthesis of α-pinene in fruits. In addition, promoter analysis revealed the presence of multiple regulatory elements related to stress response in the promoter regions of both genes. The findings of this study can provide a reference for the functional study of terpene synthase genes and new genetic elements for pinene biosynthesis.

A previous study indicated that long non-coding RNA X-inactive-specific transcript (XIST) promoted ethanol-induced HSCs autophagy and activation. Considering the critical role of HSC activation in hepatic fibrosis, the aim of the present study was to reveal the exact role of XIST in liver fibrosis and its underlying mechanism. The expression of XIST in the liver from CCL 4 -induced mice and control mice as well as human fibrotic liver tissue and healthy liver tissue was examined. The mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (MMP), and mitochondrial morphology were measured to assess the mitochondrial damage. The relationship between XIST and miR-539-3p as well as between miR-539-3p and ADAMTS5 was verified by a dual-luciferase reporter assay. The expression levels of HSCs activation markers were examined by Western blot. The results showed that the XIST was upregulated in fibrotic liver tissue, and overexpression of XIST induced mitochondrial dysfunction in hepatocytes. miR-539-3p directly targeted XIST, and ADAMTS5 mRNA was a downstream target of miR-539-3p. Knockdown of miR-539-3p led to an increased mitochondrial damage in hepatocytes in terms of reduced mitochondrial length, decreased MMP, and increased ROS production. However, the depletion of ADAMTS5 reversed the regulatory effect of XIST on mitochondrial damage in hepatocytes and the activation of HSCs. Our study revealed the critical role of the XIST/miR-539-3p/ADAMTS5 axis in regulating mitochondrial damage in hepatocytes and the activation of HSCs. This study may provide a potential therapeutic strategy for the treatment of liver fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Large-sized crystals of the quaternary iodate NaVO 2 (IO 3 ) 2 (H 2 O) (NVIO) with centimeter-scale dimensions (23 mm × 18 mm × 6 mm as a representative) have been successfully grown by the top-seeded hydrothermal method. Linear optical properties have been measured, including the optical transmission spectrum and refractive index. The NVIO crystal possesses an optical window with high transmittance (above 80%) over the range of 500-1410 nm and exhibits strong optical anisotropy with large birefringence Δ n ( n z - n x ) of 0.1522 at 1064 nm and 0.1720 at 532 nm. Based on the measured refractive indices, the phase-matching conditions for second-harmonic generation (SHG) have been calculated, and SHG devices have further been fabricated along the calculated type I and type II phase-matching directions of (θ = 39.0°, φ = 3.8°) and (θ =53.8°, φ = 1.3°). Laser experiments of extra-cavity frequency doubling have been performed on these NVIO devices. It has been confirmed that the effective SHG conversion from 1064 to 532 nm could be achieved with an energy conversion efficiency of 8.1%. Our work demonstrates that large-sized NVIO crystals are promising in the frequency-doubling application.

Background and Objective: The application of wedge-shaped bone grafts can increase the biomechanical stability of knee during the medial open-wedge high tibial osteotomy (MOWHTO) by reducing the von Mises stress of the medial plate and lateral cortical hinge area. However, the optimal position of bone grafts it remains unclear, so we aimed to determine search for the optimal position of the bone grafts in MOWHTO by using finite element analysis., Methods: In the finite element analysis, MOWHTO models were established with three different osteotomy distraction heights and assembled into four groups according to different conditions, including the no bone grafts (NBG) group, the anterior bone grafts (ABG) group, the middle bone grafts (MBG) group, and the posterior bone grafts (PBG) group. Based on previous studies, 600 N and 1800 N loads were applied to the knee joint to simulate the static forces during a double and single leg stance to measure the von Mises stress of the medial implant area and lateral hinge area, the maximum displacement of different models, the relative displacement of the osteotomy area and the stress distribution in the bone grafts., Results: Compared to the NBG and ABG groups, the stress of the lateral cortical hinge area and the medial implate area was significantly lower in the PBG group. For example, under the 600N force load, when the height of the osteotomy area was 10 mm, 15 mm, and 20 mm, the maximum von Mises stress of the medial implate area and lateral cortical hinge area in the NBG group were 140, 141, 172, and 53, 57, 60 MPa, respectively. Compared with the NBG group, the maximum von Mises stress of the medial implate area and lateral cortical hinge area in the PBG group were reduced by 45%, 56%, 63% and 14%, 39%, 68% at distraction height of 10 mm, 15 mm, and 20 mm, respectively. The bone grafts in the posterior parts provide the best stability,with the stress of the middle and posterior bone grafts are mainly concentrated in the edge., Conclusions: The posterior part of the osteotomy area is the best position for bone graft placement since it provides optimal stability and reduces von Mises stress in the medial plate and lateral cortex hinge area, with the stress of the posterior bone grafts mainly concentrated in the edge. These findings guide bone graft placement sites in clinical surgery and are a basis for future research on bone graft materials and structures in MOWHTO., Competing Interests: Declaration of Competing Interest We did not have any financial and personal relationship with other people or organization., (Copyright © 2022. Published by Elsevier B.V.)

Pseudomonas plecoglossicida is the pathogen responsible for visceral white spot disease in large yellow croaker ( Larimichthys crocea ) and orange-spotted grouper ( Epinephelus coioides ). Previously, RNA sequencing showed that P. plecoglossicida flgK gene expression was significantly up-regulated in orange-spotted grouper spleens during infection. To explore the role of flgK in P. plecoglossicida pathogenicity, RNA interference (RNAi) was performed to silence the P. plecoglossicida flgK gene, and the mutant ( flgK -RNAi strain) with the best silencing efficiency (89.40%) was chosen for further study. Results showed that flgK gene silencing significantly attenuated P. plecoglossicida motility, adhesion, and biofilm formation. Compared to those fish infected with the wild-type strain of P. plecoglossicida , orange-spotted grouper infected with the flgK -RNAi strain showed a 55% increase in the survival rate and a one-day delay in time of first death, with fewer pathogens in the spleen and fewer white spots on the spleen surface. RNAi of flgK significantly affected the transcriptome and metabolome of the spleen in infected orange-spotted grouper. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the C-type lectin receptor signaling pathway was the most significantly changed immune-related pathway and the mitogen-activated protein kinase (MAPK) signaling pathway was related to multiple immune-related pathways. Furthermore, arginine biosynthesis and glycerophospholipid metabolism were the most significantly changed metabolism-related pathways. These findings suggest that flgK is a virulence gene of P. plecoglossicida . Furthermore, flgK appears to be involved in the regulation of motility, adhesion, and biofilm formation in P. plecoglossicida , as well as in the regulation of inflammatory and immune responses of orange-spotted grouper to P. plecoglossicida infection.

Introduction: As a common autoimmune disease with the characteristic of early complication, primary biliary cholangitis (PBC) leads to an increasing number of mortalities among people with end-stage liver disease (ESLD) waiting for liver transplantation. Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for PBC, and a good response to treatment could acquire an ideal prognosis. Patients with poor UDCA response usually have more adverse outcomes and worse survival, therefore, the management of this group become a major consideration., Areas Covered: Due to the complexity of race and environment for PBC, different criteria for UDCA response exhibit various predictive performances. Factors affecting UDCA response conditions include gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities, while no agreement has been reached. In this review, we mainly focus on cellular senescence, immune-mediated damage, and vitamin D deficiency as possible mechanisms for UDCA non-responders., Expert Opinion: The pathogenesis of PBC has yet to be clarified. Immunology-related mechanisms and therapy targets ought to be the main effort made for further study. Irrespective of the response condition, UDCA is recommended for routine administration in all PBC patients without contraindication. Ongoing clinical trials of second-line and additional therapy exhibit promising prospects.

The government of the Northern Song Dynasty collated and annotated Su Wen four times from 1026-1118. It examined a large number of errors in the collated edition by Wang Bing, and corrected the edition. However, for reasons of time and conditions, there still existed some mistakes, even serious ones, such as the selection of the original texts and the determination of the titles and many other details as well. Among these mistakes, the one which seriously prevented learning medical classics for following generations was that the quoted texts from early medical books were modified based on the Su Wen collated by Wang Bing and Jia Yi Jing on Acupuncture and Moxibustion. This led to the distortion of some early important medical books. This paper examines the re-collation of Su Wen by the officials of the Song Dynasty in a specific historical background and environment, focuses on the errors that have not been perceived today, and pays attention to the investigation and analysis of the causes of those errors, so as to provide a reference for collation of ancient medical classics today.

Background: Sjögren's syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity., Purpose: To assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF)., Material and Methods: Sixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation., Results: ALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE., Conclusion: SjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

Background and Purpose: Gadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability., Methods: Consecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability., Results: Fifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P < 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity)., Conclusion: The LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Huang, Huang, Lu, Luo, Cai, Liu and Wang.)

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo . Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Liu, Zhou, Huang, Shi, Hou, Lu, Yu, Chen and Guo.)

Background: The dynamic balance of osteoblast and osteoclast is critical for bone homeostasis and overactive osteoclastic function may lead to osteoporosis. Activating transcription factor 1 (ATF1) is involved in osteoclastogenesis. However, the detailed mechanisms remain to be explored., Methods: RAW264.7 cells were used and induced toward osteoclast by RANKL administration. We performed flow cytometry, CCK-8 assay and tartrate-resistant acid phosphatase (TRAP) staining to examine cell apoptosis, proliferation and differentiation of RAW264.7 cells, respectively. Mice were subjected to ovariectomy to induce osteoporosis. Micro CT, HE staining and TRAP staining were performed to evaluate bone loss in the OVX mouse model. Bioinformatics methods, luciferase assays and Chromatin Immunoprecipitation (ChIP) were used to predict and validate the interaction among ATF1, miR-214-5p, and ITGA7., Results: ATF1 and miR-214-5p were up-regulated while ITGA7 was inhibited in RANKL-induced osteoclasts. MiR-214-5p was transcriptionally activated by ATF1. ATF1 knockdown suppressed osteoclast formation by miR-214-5p inhibition. ITGA7 was the direct target of miR-214-5p. Knockdown of miR-214-5p abolished osteoclastogenesis, which was reversed by ITGA7 knockdown. In OVX model, miR-214-5p knockdown suppressed osteoclast differentiation and prevented bone loss., Conclusion: ATF1/miR-214-5p/ITGA7 axis regulated osteoclast formation both in vivo and in vitro, thereby affecting OVX-induced bone resorption in mice. Knockdown of ATF1 might be a promising strategy to manage osteoporosis., (© 2022. The Author(s).)

To cooperate with the popularization and application of the China national standard Nomenclature and Location of Meridian Points (GB/T 12346 -2021), this study introduced the differences between the 2021 version and the 2006 version, and explained the principles of the revision and the changes in the standard name, terminology, definition and the expression of meridian points' body regions. In addition, the revision of the specific contents, including the adjustment of "bone proportional cun" of several meridian points and the revision basis of location of some meridian points were explained.

Liquid droplets rectors have been used in clinical diagnosis, high throughput screening and bioassay. However, it is challenging for droplet reactors to be used in practical applications due to the difficulty of uniformly mixing ultrasmall volumes of samples and the lack of rapid and high-precision detection protocols. Here, we have developed an acoustic droplet system for rapid and efficient biological detection and chemical screening. By employing acoustic wave devices, rapid and nondestructive uniform mixing of ∼nL-μL droplets can be achieved. By the acoustophoretic force, the perturbation of the droplets can quickly concentrate the sample and increase the detection limit by five times. Through the color reaction and the coordinated detection of photodiodes, we have developed a biomarker detection protocol with short reaction time and high accuracy. As a proof-of-concept application, we demonstrated that this system can detect ultrasmall or low-abundance samples faster and more accurately, highlighting its wide application in analytical chemistry, basic research, and clinical medicine.

It has been the consensus of the academic community that the doctor DOU Han-qing in Jin-Yuan Dynasty was the pioneer of point to point penetration acupuncture method.The contents of several texts in Yuan-Ming-Qing Dynasties were combed on the basis of Dou Taishi Zhenjing (《》).The paradigm,the acupoints,basic elements and the characteristics of the main treatment of diseases were discussed,and the relationship between the point to point penetration acupuncture method with the penetration acupuncture method has been tried to distinguish from the perspective of technical philosophy. It was found that the specifications and quantity of the 28 "penetration and to" cases in Dou Taishi Zhenjing (《》)were sufficiently exemplary for future generations, and were the source documents of Yuan-Ming-Qing's texts,which basically followed its specifications and content and developed.For example,the Yulong Poetries (《》)in the books of Bianque Shenying Zhenjiu Yulong Jing (《》), Zhenjiu Dacheng (《》), Zhenfang Liuji (《》).The 37 cases in Zhenfang Liuji (《》) were the most in several texts.The 31 cases in Xunjing Kaoxue Bian (《》)had the characteristics of DOU Han-qing, YANG Ji-zhou and LING Yun, who developed the opposite direction penetration method with two or more needles on DOU Han-qing's one needle.There were five basic elements in the point to point penetration acupuncture method:the needle pri-cking inch(depth), the needle pricking angle, the needle pricking direction, the starting acupoint, the end acupoint.This method in Dou Taishi Zhenjing (《》)mostly treated local diseases and symptoms,some acupoints below the elbows and knees also treated far-end diseases.The point to point penetration acupuncture method has a specific intention structure, which cannot be confused with the penetration acupuncture method.

Purpose: The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance., Methods: Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed., Results: Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients., Conclusions: Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

An indicator displacement assay, namely polymeric PNPY-n/UD consisting of a cationic polynorbornene backbone with pyridinium functional groups (PNPY-1,2,3) and an anionic uranine dye (UD) as an indicator, has been developed for highly sensitive "turn-on" fluorescence sensing of ATP. While PNPY-1/UD itself is non-emissive, a bright green fluorescence signal was observed in the presence of ATP [ K a = 2.17 × 10 5 M -1 , LOD = 5.7 nM]. The potential of a highly photostable system PNPY-1/UD was also validated in detecting ATP levels in live-cell imaging applications.