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Purpose: This study aims to assess the diagnostic efficacy of Korean Thyroid imaging reporting and data system (K‐TIRADS), S‐Detect software and contrast‐enhanced ultrasound (CEUS) when employed individually, as well as their combined application, for the evaluation of thyroid nodules, with the objective of identifying the optimal method for diagnosing thyroid nodules. Methods: Two hundred and sixty eight cases pathologically proven of thyroid nodules were retrospectively enrolled. Each nodule was classified according to K‐TIRADS. S‐Detect software was utilized for intelligent analysis. CEUS was employed to acquire contrast‐enhanced features. Results: The area under curve (AUC) values for diagnosing benign and malignant thyroid nodules using K‐TIRADS alone, S‐Detect software alone, CEUS alone, the combined application of K‐TIRADS and CEUS, the combined application of S‐Detect software and CEUS were 0.668, 0.668, 0.719, 0.741, and 0.759, respectively (p < 0.001). The sensitivity rate of S‐Detect software was 89.9% (p < 0.001). It was the highest of the five diagnostic methods above. Conclusion: The utilization of S‐Detect software can be served as a powerful tool for early screening. Notably, the combined utilization of S‐Detect software with CEUS demonstrates superior diagnostic performance compared to employing K‐TIRADS, S‐Detect software, CEUS used individually, as well as the combined application of K‐TIRADS with CEUS. [ABSTRACT FROM AUTHOR]

In fish species, there is limited analysis of signature transcriptome profiles at the single‐cell level in gonadal cells. Here, the molecular signatures of distinct ovarian cell categories in adult Nile tilapia (Oreochromis niloticus) were analysed using single‐nucleus RNA sequencing (snRNA‐seq). We identified four cell types (oogonia, oocytes, granulosa cell, and thecal cell) based on their specifically expressed genes and biological functions. Similarly, we found some key pathways involved in ovarian development that may affect germline–somatic interactions. A cell‐to‐cell communication network between the distinct cell types was constructed. We found that the bidirectional communication is mandatory for the development of germ cells and somatic cells in fish ovaries, and the granulosa cells and thecal cells play a central regulating role in the cell network in fish ovary. Additionally, we identified some novel candidate marker genes for various types of ovarian cells and also validated them using in situ hybridization. Our work reveals an ovarian atlas at the cellular and molecular levels and contributes to providing insights into oogenesis and gonad development in fish. [ABSTRACT FROM AUTHOR]

Periprosthetic femoral fractures (PPFFs) following total hip arthroplasty (THA) present a significant clinical challenge due to their increasing incidence with an aging population and evolving surgical practices. Historically, classifications were primarily based on anatomical fracture location, the stability of the implant, and bone quality surrounding the implant. We critically analyzed 25 classification systems, highlighting the emergence and adaptations of key systems such as the Vancouver classification system (VCS) and the Unified classification system (UCS), which are lauded for their simplicity and effectiveness yet require further refinement. VCS, developed in 1995, categorizes fractures based on the site, implant stability, and bone quality, and remains widely used due to its robust applicability across different clinical settings. Introduced in 2014, UCS expands the VCS to encompass all periprosthetic fractures with additional fracture types, aiming for a universal application. Despite their widespread adoption, these systems exhibit shortcomings, including the incomplete inclusion of all PPFF types and the imprecise assessment of implant stability and surrounding bone loss. These gaps can result in misclassification and suboptimal treatment outcomes. This paper suggests the necessity for ongoing improvements in classification systems to include emerging fracture types and refined diagnostic criteria, ensuring that they remain relevant to contemporary orthopedic practices and continue to facilitate the precise tailoring of treatment to patient‐specific circumstances. This comprehensive historical review serves as a foundation for future innovations in classification systems, ultimately aiming to standardize PPFF treatment and improve patient prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Galeruca daurica has become a new pest on the Inner Mongolia grasslands since an abrupt outbreak in 2009 caused serious damage. As a pupa indicator during insect metamorphosis, the early response gene of the ecdysone signaling pathway, Broad‐Complex (Br‐C), plays a vital role in the growth and development of insects. MicroRNAs (miRNAs) are small non‐coding RNAs which mediate various biological activities, but it is unknown whether and how Br‐C is regulated by miRNAs. RESULTS: Temporal expression profiles revealed that miR‐285 and Br‐C basically displayed an opposite trend during larval–adult development, and Br‐C was sharply up‐regulated on the last day of final‐instar larvae while miR‐285 was significantly down‐regulated. Both dual‐luciferase reporter assay and miRNA–mRNA interaction assay indicated that miR‐285 interacts with the coding sequence of Br‐C and represses its expression. Not only overexpression but also downexpression of miR‐285 led to the failure of larval to pupal to adult metamorphosis. In addition, both overexpression of miR‐285 and silence of Br‐C inhibited the expression of Br‐C and other ecdysone signaling pathway genes, including E74, E75, ECR, FTZ‐F1, and HR3. On the contrary, suppressing miR‐285 obtained opposite results. Further experiments showed that 20‐hydroxyecdysone down‐regulated miR‐285 and up‐regulated Br‐C and above‐mentioned genes, whereas juvenile hormone alalogue (JHA) resulted in opposite effects. CONCLUSION: Our results reveal that miR‐285 is involved in mediating the metamorphosis in G. daurica by targeting Br‐C in the ecdysone signaling pathway. miR‐285 and its target Br‐C could be as a potential target for G. daurica management. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this paper, the electrical performance of a‐Si TFT product on adjustable frequency display is studied. It is found that panel flicker behavior is related to a‐Si channel characteristics, which is related to the TFT Cgs capacitance increase at low display frequency. And it is also found that the relationship between brightness fluctuations and TFT leakage current affected by Poole‐Frenkel effect. By optimizing TFT process parameter to reduce the change of Cgs capacitance and reduce TFT leakage current in Poole‐Frenkel region, panel flicker performance is obviously improved. As a result, gaming display product can meet the G‐sync optical standard requirement. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Experimental models are essential tools in neurodegenerative disease research. However, the translation of insights and drugs discovered in model systems has proven immensely challenging, marred by high failure rates in human clinical trials. METHODS: Here we review the application of artificial intelligence (AI) and machine learning (ML) in experimental medicine for dementia research. RESULTS: Considering the specific challenges of reproducibility and translation between other species or model systems and human biology in preclinical dementia research, we highlight best practices and resources that can be leveraged to quantify and evaluate translatability. We then evaluate how AI and ML approaches could be applied to enhance both cross‐model reproducibility and translation to human biology, while sustaining biological interpretability. DISCUSSION: AI and ML approaches in experimental medicine remain in their infancy. However, they have great potential to strengthen preclinical research and translation if based upon adequate, robust, and reproducible experimental data. Highlights: There are increasing applications of AI in experimental medicine.We identified issues in reproducibility, cross‐species translation, and data curation in the field.Our review highlights data resources and AI approaches as solutions.Multi‐omics analysis with AI offers exciting future possibilities in drug discovery. [ABSTRACT FROM AUTHOR]

Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress. Opportunities arise at multiple stages in the therapy pipeline and the growing availability of large medical data sets opens possibilities for big data analyses to answer key questions in clinical and therapeutic challenges. However, before this goal is reached, several challenges need to be overcome and only a multi‐disciplinary approach can promote data‐driven decision‐making to its full potential. Herein we review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation. [ABSTRACT FROM AUTHOR]

An efficient strategy for the identification of potential nephroprotective substances in Zhu‐Ling decoction has been established with the integration of absorbed components characterization, pharmacokinetics, and activity evaluation. A qualitative method was developed to characterize the chemical constituents absorbed components in vivo of Zhu‐Ling decoction by using ultra‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry. A quantitative method was established and validated for the simultaneous determination of eight compounds in rat plasma by using ultra‐performance liquid chromatography‐triple quadruple tandem mass spectrometry. Finally, the nephroprotective activities of absorbed components with high exposure were assessed by cell survival rate, superoxide dismutase, and malondialdehyde activities in hydrogen peroxide–induced Vero cells. As a result, 111 compounds in Zhu‐Ling decoction and 36 absorbed components were identified in rat plasma and urine, and poricoic acid A, poricoic acid B, alisol A, 16‐oxo‐alisol A, and dehydro‐tumulosic acid had high exposure levels in rat plasma. Finally, poricoic acid B, poricoic acid A, 16‐oxo‐alisol A, and dehydro‐tumulosic acid showed remarkable nephroprotective activity against Vero cells damage induced by hydrogen peroxide. Besides, superoxide dismutase and malondialdehyde activities were obviously regulated in hydrogen peroxide–induced Vero cells by treatment with the four compounds mentioned above. Therefore, these four compounds were considered to be effective substances of Zhu‐Ling decoction due to their relatively high exposure in vivo and biological activity. This study provided a chemical basis for the action mechanism of Zhu‐Ling decoction in the treatment of chronic kidney diseases. [ABSTRACT FROM AUTHOR]

Exploring the frequency and distribution pattern of polyploid species in geographic parameters is of significance in understanding the mechanisms of polyploid speciation and evolutionary drivers of biodiversity. We here explored polyploid and paleopolyploid incidence frequency in a scale of 100 × 100 km grids in China. We found 33% of angiosperm species are polyploidy in China, and 23% of polyploid speciation. Western China and eastern China showed a significantly different polyploid and paleopolyploid frequency, with an evolutionary cradle of polyploid angiosperms in the Qinghai–Tibetan plateau. Herbaceous species exhibited higher polyploid frequency but lower paleopolyploid frequency than woody species, indicating the former experienced more rapid differentiation and speciation than the latter. Our results indicate that western China is an evolutionary cradle for polyploid angiosperms where harsh environment facilitates the establishment and survival of polyploids, while polyploid lineages tend to rediploidize to be diploids with sufficient time in suitable environment. [ABSTRACT FROM AUTHOR]

Objective: The isolated second metacarpal base fracture‐dislocations in adults are rare, and the traditional main treatments include closed reduction with the plaster or splint and open reduction with internal fixation (ORIF). However, closed reduction with the plaster or splint is not solid enough and ORIF can damage the surrounding important tissues. The purpose of this study was to explore the clinical outcomes of closed reduction and external fixation (CREF) for the treatment of isolated second metacarpal base fracture‐dislocations. Methods: Ten patients who suffered isolated second metacarpal base fracture‐dislocations between January 1, 2010, and February 1, 2020, were reviewed. All of the patients were treated by CREF. Radiographs and computed tomography scans were performed regularly after the operation. The grip and pinch strength, visual analog scale (VAS) pain score, American Society for Surgery of the Hand total active movement (TAM) and total active flexion (TAF) scores, Cooney score, Sollerman hand function test (SHFT) score, QuickDASH score, and range of motion of the index finger were recorded at the last follow‐up visit to evaluate functional recovery; the injured and healthy hands were compared and we also recorded postoperative complications. The paired samples t‐test was used to compare the healthy and injured sides. Results: The patients were followed up for a median of 29.50 ± 4.2 months. There were no significant differences in the grip strength, pinch strength, angle of proximal interphalangeal joint (PIPJ) flexion, or angle of distal interphalangeal joint (DIPJ) flexion between the injured and healthy sides at the final follow‐up visit (all p > 0.05). The mean TAM (268.20 ± 4.21) and TAF scores (270.60 ± 4.17) on injured side were significantly lower than those on healthy side (all p < 0.05). The mean Cooney score (93.50 ± 7.47) and SHFT score (78.50 ± 1.08) on injured side were lower, while the mean QuickDASH score (7.05 ± 3.11) on injured side was higher than those on healthy side (all p < 0.05). The mean VAS pain score was 0.50 ± 0.53 on injured side. There were no significant postoperative complications except for traumatic arthritis in one patient without obvious clinical symptoms. Conclusion: CREF achieves the satisfactory curative effect, and the patients obtain the good functional recovery without significant postoperative complications. CREF is a safe and effective treatment for isolated second metacarpal base fracture‐dislocations with satisfactory clinical outcomes. [ABSTRACT FROM AUTHOR]

The presence of hepatitis B virus (HBV) covalently closed circular (ccc) DNA (cccDNA), which serves as a template for viral replication and integration of HBV DNA into the host cell genome, sustains liver pathogenesis and constitutes an intractable barrier to the eradication of chronic HBV infection. The current antiviral therapy for HBV infection, using nucleos(t)ide analogues (NAs), can suppress HBV replication but cannot eliminate integrated HBV DNA and episomal cccDNA. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is a powerful genetic tool that can edit integrated HBV DNA and minichromosomal cccDNA for gene therapy, but its expression and delivery require a viral vector, which poses safety concerns for therapeutic applications in humans. In the present study, we used synthetic guide RNA (gRNA)/Cas9‐ribonucleoprotein (RNP) as a nonviral formulation to develop a novel CRISPR/Cas9‐mediated gene therapy for eradicating HBV infection. We designed a series of gRNAs targeting multiple specific HBV genes and tested their antiviral efficacy and cytotoxicity in different HBV cellular models. Transfection of stably HBV‐infected human hepatoma cell line HepG2.2.15 with HBV‐specific gRNA/Cas9 RNPs resulted in a substantial reduction in HBV transcripts. Specifically, gRNA5 and/or gRNA9 RNPs significantly reduced HBV cccDNA, total HBV DNA, pregenomic RNA, and HBV antigen (HBsAg, HBeAg) levels. T7 endonuclease 1 (T7E1) cleavage assay and DNA sequencing confirmed specific HBV gene cleavage and mutations at or around the gRNA target sites. Notably, this gene‐editing system did not alter cellular viability or proliferation in the treated cells. Because of their rapid DNA cleavage capability, low off‐target effects, low risk of insertional mutagenesis, and readiness for use in clinical application, these results suggest that synthetic gRNA/Cas9 RNP‐based gene‐editing can be utilized as a promising therapeutic drug for eradicating chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background and Purpose: Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro‐immune communication. Neuronal mechanism‐based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro‐immune mechanism. Experimental Approach: Pharmacological intervention, immunofluorescence, RNA‐sequencing, genetic modification and immunoassay were performed to dissect the neuro‐immune basis of itch and inflammation in atopic dermatitis‐like mouse model and in patients. Key Results: Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)‐induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX‐314, a charged NaV blocker that enters through pathologically activated large‐pore ion channels and selectivity inhibits a subpopulation of sensory neurons, has the same effects as lidocaine in atopic dermatitis model. Genetic silencing NaV1.8‐expressing sensory neurons was sufficient to restrict cutaneous inflammation and itch in the atopic dermatitis model. However, pharmacological blockade of TRPV1‐positive nociceptors only abolished persistent itch but did not affect skin inflammation in the atopic dermatitis model, indicating a difference between sensory neuronal modulation of skin inflammation and itch. Inhibition of activity‐dependent release of calcitonin gene‐related peptide (CGRP) from sensory neurons by lidocaine largely accounts for the therapeutic effect of lidocaine in the atopic dermatitis model. Conclusion and Implications: NaV1.8+ sensory neurons play a critical role in pathogenesis of atopic dermatitis and lidocaine is a potential anti‐inflammatory and anti‐pruritic agent for atopic dermatitis. A dissociable difference for sensory neuronal modulation of skin inflammation and itch contributes to further understanding of pathogenesis in atopic dermatitis. [ABSTRACT FROM AUTHOR]

In this work, high efficiency and multifunctional poly(vinyl alcohol‐co‐ethylene) nanofiber, Ag particle, and polypropylene (PP) meltblown nonwoven substrate composite (NF@Ag) air filters by a simple spray coating method and subsequent UV irradiation treatment are demonstrated. The water vapor transmission rate of the NF@Ag‐4 air filter is 4753.36 ± 316.75 g/(m2 d), which is higher than that of commercial PP nonwoven (4240.71 ± 354.36 g/(m2 d)). It is can be explained that the NF@Ag‐4 air filter is a Janus structure with asymmetric wettability, which enhances moisture permeability, thereby improving comfort while wearing. The NF@Ag‐2 air filter exhibits high filtration efficiency (95.80 ± 0.89%) and relatively low pressure drop (122.00 ± 1.73 Pa) without relying on the electrostatic adsorption effect. The resulting NF@Ag air filters display excellent antibacterial properties against Escherichia coli and Staphylococcus aureus, photothermal disinfection, and thermal insulation performance. Furthermore, the as‐prepared NF@Ag air filters can be simply patterned and designed as respiration monitoring sensors to precisely detect the respiratory activity and health of the human being. Therefore, it is believed that these multifunctional air filters will have good potential for applications in the removal of particular matters and breathable wearable electronic devices. [ABSTRACT FROM AUTHOR]

Codonopsis radix was commonly used as food materials or herbal medicines in many countries. However, the comprehensive analysis of chemical constituents, and in vivo xenobiotics of Codonopsis radix remain unclear. In the present study, an integrated strategy with feature‐based molecular networking using ultra‐high‐performance liquid chromatography coupled with mass spectrometry was established to systematically screen the chemical constituents and the in vivo xenobiotics of Codonopsis radix. A step‐by‐step manner based on a composition database, visual structure classification, discriminant ions, and metabolite software prediction was proposed to overcome the complexities due to the similar structure of chemical constituents and metabolites of Codonopsis radix. As a result, 103 compounds were tentatively characterized, 20 of which were identified by reference standards. Besides, a total of 50 xenobiotics were detected in vivo, including 26 prototypes and 24 metabolites, while the metabolic features of the pyrrolidine alkaloids were elucidated for the first time. The metabolism reactions of pyrrolidine alkaloids and sesquiterpene lactones included oxidation, methylation, hydration, hydrogenation, demethylation, glucuronidation, and sulfation. This study provided a generally applicable approach to the comprehensive investigation of the chemical and metabolic profile of traditional Chinese medicine and offered reasonable guidelines for further screening of quality control indicators and pharmacodynamics mechanism of Codonopsis radix. [ABSTRACT FROM AUTHOR]

Objectives: The operative microscope (OM) has revolutionized the field of modern spine surgery, however, it remains limited by several drawbacks. Recently, the exoscope (EX) system has been designed to assistant spine surgery. It provides a three‐dimensional (3D) high‐definition (HD) operative experience and becomes an alternative to the OM. The aim of the study was to evaluate the clinical outcomes, advantages and limitations of EX‐assisted minimally invasive transforaminal lumbar interbody fusion (EMIS‐TLIF) and OM‐assisted MIS‐TLIF (OMIS‐TLIF). Methods: The clinical outcomes were assessed in 47 patients with lumbar degenerative diseases (LDD) who underwent MIS‐TLIF assisted with the OM or EX between January 2019 and September 2020. A total of 22 were treated with EMIS‐TLIF, and 25 received OMIS‐TLIF. Perioperative parameters (including sex, age, number of fusion levels and body mass index), perioperative parameters (operation time, intraoperative blood loss, postoperative drainage, postoperative hospitalization stay, and duration of follow‐up), visual analogue scale (VAS) of back pain, VAS of leg pain, Oswestry disability index (ODI) scores and clinical outcomes were assessed and compared. Image quality, handling of equipment, ergonomics, 3D glasses and educational usefulness were scored according to a questionnaire. Results: Operation time in the OMIS‐TLIF group (121.92 ± 16.92 min) was significantly increased compared with that in the EMIS‐TLIF group (111.00 ± 19.87 min) (P < 0.05). The VAS of the back pain and ODI scores in the EMIS‐TLIF group were significantly lower compared with the OMIS‐TLIF group at 1 week postoperatively (P < 0.05). The good‐excellent outcomes rate was 90.91% in the EMIS‐TLIF group and 88.00% in the OMIS‐TLIF group, and there was no significant difference. A total of 44 visits completed the questionnaire. The results of the questionnaire showed that the EX has exhibited advantages regarding handing of equipment, ergonomics and educational usefulness, and comparable image quality as compared with the OM, however, operating surgeons complained uncomfortable sensation when wearing 3D glasses. Conclusions: The EMIS‐TLIF was a safe and effective procedure in the management of LDD as compared with the OMIS‐LIF. Meanwhile, EMIS‐TLIF might resulted in a short operation time. [ABSTRACT FROM AUTHOR]

In this study, we investigated the role of calcium/calmodulin‐dependent protein kinase II (CaMKII) in contraction‐stimulated glucose uptake in skeletal muscle. C2C12 myotubes were contracted by electrical pulse stimulation (EPS), and treadmill running was used to exercise mice. The activities of CaMKII, the small G protein Rac1, and the Rac1 effector kinase PAK1 were elevated in muscle by running exercise or EPS, while they were lowered by the CaMKII inhibitor KN‐93 and/or small interfering RNA (siRNA)‐mediated knockdown. EPS induced the mRNA and protein expression of the Rac1‐GEF Kalirin in a CaMKII‐dependent manner. EPS‐induced Rac1 activation was lowered by the Kalirin inhibitor ITX3 or siRNA‐mediated Kalirin knockdown. KN‐93, ITX3, and siRNA‐mediated Kalirin knockdown reduced EPS‐induced glucose uptake. These findings define a CaMKII‐Kalirin‐Rac1 signaling pathway that contributes to contraction‐stimulated glucose uptake in skeletal muscle myotubes and tissue. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold‐based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate‐based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration‐dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+‐releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post‐operation compared to the controls (blank conduits or conduits filled with Mg2+‐absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+‐releasing hydrogel compared to that in the control groups. In summary, the Mg2+‐releasing hydrogel combined with the 3D‐engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repair of challenging peripheral nerve injuries is proposed. [ABSTRACT FROM AUTHOR]

In the present study, a specific and sensitive approach using ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated for the quantitative analysis of 14 constituents in rat plasma, liver, and heart. The method was fully validated and successfully applied to pharmacokinetic, hepatic disposition, and heart tissue distribution studies of 14 compounds after the oral administration of Qi‐Li‐Qiang‐Xin capsule. Ginsenoside Rb1, alisol A, astragaloside IV, and periplocymarin were found to be highly exposed in rat plasma, while toxic components such as hypaconitine, mesaconitine, and periplocin had low circulation levels in vivo. Moreover, sinapine thiocyanate, neoline, formononetin, calycosin, and alisol A exhibited significant liver first‐pass effects. Notably, high levels of alisol A, periplocymarin, benzoylmesaconine, and benzoylhypaconine were observed in the heart. Based on high exposure and appropriate pharmacokinetic features in the systemic plasma and heart, astragaloside IV, ginsenoside Rb1, periplocymarin, benzoylmesaconine, benzoylhypaconine, and alisol A can be considered as the main potentially effective components. Ultimately, the results provide relevant information for discovery of effective substances, as well as further anti‐heart failure action mechanism investigations of Qi‐Li‐Qiang‐Xin capsule. [ABSTRACT FROM AUTHOR]

In tracheal tissue engineering, the construction of tracheal scaffolds with adequate biodegradable mechanical capacity and biological functions that mimic the structure of a natural trachea is challenging. To explore the feasibility of preparing biomimetic degradable scaffolds with C‐type cartilage rings and an inner tracheal wall of polycaprolactone and silk fibroin. A mold was made according to the diameter of a rabbit trachea, and a silk fibroin tube and polycaprolactone ring attached to the tube were obtained by solution casting. The ring was fixed to the tube at a specific spacing using electrostatic spinning technology to construct a biomimetic tracheal scaffold; its porous structure was observed by scanning electron microscopy, its degradation properties were determined by in vitro enzymatic hydrolysis and its mechanical properties were obtained by pressure testing. The composite scaffold was transplanted subcutaneously into a rabbit model, and the scaffold was taken at 1, 2, and 4 weeks after surgery for sectioning to observe pre‐vascularization. The Medical Ethics Committee of Guangdong Provincial People's Hospital approved the study. The general view of the biomimetic scaffold: the polycaprolactone ring was fixed firmly on the outer wall of the silk fibroin tube; the two corresponded in size, and they fitted closely. The surface of the polycaprolactone ring was smooth and dense, while the surface of the silk fibroin tube could be seen as a uniform porous structure. Scanning electron microscopy showed that the surface and profile of the fibroin tube had a uniform pore size and distribution. The pores were connected to form a network. In vitro, enzymatic hydrolysis experiments confirmed that the fibroin was degraded easily, with most being degraded at the end of week 1. The degradation slowed at 2, 3, and 4 weeks, while the degradation of polycaprolactone was extremely slow. A compression test showed that the compressive resistance of the silk fibroin–polycaprolactone biomimetic scaffolds was much better than that of the rabbit trachea at close thickness. In the tissue staining experiments, as the material degraded, fibrous tissues and blood vessels grew to replace the material, allowing the scaffold to obtain a blood supply and better mechanical properties. A quantitative analysis of CD31 showed that the results for the vascularization of the scaffold were better at 4 weeks than at 2 weeks following subcutaneous grafting (P <.05). The results confirmed that it is feasible to prepare porous, degradable silk fibroin–polycaprolactone biomimetic scaffolds with good mechanical properties and epithelial biological functions by mold casting. [ABSTRACT FROM AUTHOR]

The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene‐related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type‐H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES‐enhanced osteoporotic fracture healing. This proof‐of‐concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration. [ABSTRACT FROM AUTHOR]

Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress‐mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells—the major effectors of host adaptive immunity against infection and malignancy—is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a single oxygen (1O2) only at telomeres or mitochondria in Jurkat T cells. We found that targeted 1O2 production at telomeres triggered not only telomeric DNA damage but also mitochondrial dysfunction, resulting in T cell apoptotic death. Conversely, targeted 1O2 formation at mitochondria induced not only mitochondrial injury but also telomeric DNA damage, leading to cellular crisis and apoptosis. Targeted oxidative stress at either telomeres or mitochondria increased ROS production, whereas blocking ROS formation during oxidative stress reversed the telomeric injury, mitochondrial dysfunction, and cellular apoptosis. Notably, the X‐ray repair cross‐complementing protein 1 (XRCC1) in the base excision repair (BER) pathway and multiple mitochondrial proteins in other cellular pathways were dysregulated by the targeted oxidative stress. By confining singlet 1O2 formation to a single organelle, this study suggests that oxidative stress induces dual injury in T cells via crosstalk between telomeres and mitochondria. Further identification of these oxidation pathways may offer a novel approach to preserve mitochondrial functions, protect telomere integrity, and maintain T cell survival, which can be exploited to combat various immune aging‐associated diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Effective nitrogen (N) management measures are required to control environmental problems caused by N fertilizer use in intensive maize production systems. Soil N losses associated with high precipitation and over‐fertilization in maize production can cause substantial environmental problems, whereas there is a lack of quantitative data and effective study countermeasures. A 2‐year field study was conducted in the subtropical maize production system in Southwest China to quantify N leaching under varying N application rates of 0, 90, 180, 270 and 360 kg N ha−1 yr−1. RESULTS: The results indicated that N leaching accounted for 16–38% of N fertilizer input. For farmer practice treatment (360 kg N ha−1 yr−1), N leaching loss was high at 110 kg N ha−1 yr−1and accounted for 31% of the N applied. As an indicator of the ambient water quality pollution, the grey water footprint across all treatments ranged from 376 to 1092 m3 Mg−1, with an average of 695 m3 Mg−1. Reducing N rate to agronomically optimized treatment (180 kg N ha−1 yr−1) significantly decreased N leaching by 77%, and maintained high grain yield of 8.1 Mg ha−1. The grey water footprint was reduced by 52–63% with N rates from 270 or 360 kg N ha−1 yr−1 to 180 kg N ha−1 yr−1. CONCLUSION: Nitrogen surplus (applied N rate minus N uptake by maize) resulted in higher soil residual nitrate concentration and consequently high N leaching. High precipitation and low soil pH were the main ecological factors leading to high N leaching. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The purpose of our study was to develop a simple clinical pre‐procedure risk model based on clinical characteristics for the prediction of contrast‐induced nephropathy (CIN) and major adverse cardiac events (MACEs) after percutaneous coronary intervention (PCI) in patients with diabetes. A total of 1113 patients with diabetes who underwent PCI with contrast exposure were randomized into a development group (n = 742) and a validation group (n = 371) in a 2:1 ratio. CIN was defined as an increase of either 25% or 0.5 mg/dL (44.2 μmol/L) in serum creatinine within 72 hours after contrast infusion. A simple CIN risk score based on independent predictors was established. Four variables were identified for our risk score model: LVEF < 40%, acute coronary syndrome (ACS), eGFR < 60, and contrast volume > 300 mL. Based on this new CIN risk score, the incidence of CIN had a significant trend with increased predicting score values of 5.9%, 32.9% and 60.0%, corresponding to low‐, moderate‐ and high‐risk groups, respectively. The novel risk assessment exhibited moderate discrimination ability for predicting CIN, with an AUC of 0.759 [95% CI 0.668‐0.852, P =.001] in the validation cohort. It also had similar prognostic values for one‐year follow‐up MACE (C‐statistic: 0.705 and 0.606 for new risk score and Mehran score, respectively). This novel risk prediction model could be effective for preventing nephropathy in diabetic patients receiving contrast media during surgical procedures. [ABSTRACT FROM AUTHOR]

Objective: To analyze the characteristics of menicus microstructure and to reconstruct a microstructure‐mimicing 3D model of the menicus. Methods: Human and sheep meniscus were collected and prepared for this study. Hematoxylin–eosin staining (HE) and Masson staining were conducted for histological analysis of the meniscus. For submicroscopic structure analysis, the meniscus was first freeze‐dried and then scanned by scanning electron microscopy (SEM). The porosity of the meniscus was determined according to SEM images. A micro‐MRI was used to scan each meniscus, immersed in distilled water, and a 3D digital model was reconstructed afterwards. A three‐dimensional (3D) resin model was printed out based on the digital model. Before high‐resolution micro‐CT scanning, each meniscus was freeze‐dried. Then, micro‐scale two‐dimensional (2D) CT projection images were obtained. The porosity of the meniscus was calculated according to micro‐CT images. With micro‐CT, multiple 2D projection images were collected. A 3D digital model based on 2D CT pictures was also reconstructed. The 3D digital model was exported as STL format. A 3D resin model was printed by 3D printer based on the 3D digital model. Results: As revealed in the HE and Masson images, a meniscus is mostly composed of collagen, with a few cells disseminated between the collagen fiber bundles at the micro‐scale. The SEM image clearly shows the path of highly cross‐linked collagen fibers, and massive pores exist between the fibers. According to the SEM images, the porosity of the meniscus was 34.1% (34.1% ± 0.032%) and the diameters of the collagen fibers were varied. In addition, the cross‐linking pattern of the fibers was irregular. The scanning accuracy of micro‐MRI was 50 μm. The micro‐MRI demonstrated the outline of the meniscus, but the microstructure was obscure. The micro‐CT clearly displayed microfibers in the meniscus with a voxel size of 11.4 μm. The surface layer, lamellar layer, circumferential fibers, and radial fibers could be identified. The mean porosity of the meniscus according to micro‐CT images was 33.92% (33.92% ± 0.03%). Moreover, a 3D model of the microstructure based on the micro‐CT images was built. The microscale fibers could be displayed in the micro‐CT image and the reconstructed 3D digital model. In addition, a 3D resin model was printed out based on the 3D digital model. Conclusion: It is extremely difficult to artificially simulate the microstructure of the meniscus because of the irregularity of the diameter and cross‐linking pattern of fibers. The micro‐MRI images failed to demonstrate the meniscus microstructure. Freeze‐drying and micro‐CT scanning are effective methods for 3D microstructure reconstruction of the meniscus, which is an important step towards mechanically functional 3D‐printed meniscus grafts. [ABSTRACT FROM AUTHOR]

BACKGROUND: Magnesium (Mg) fertilization is a promising practice to improve vegetable yield. However, its impacts on vegetable quality and human health have not been examined. Thus, a field experiment was conducted to investigate the effects of varying Mg fertilization rates on yield and quality of pepper (Capsicum annuum L.) fruit. Furthermore, result of the field experiment was linked to pepper consumption data from the China Health and Nutrition Survey (CHNS) in the disability‐adjusted life years (DALYs) framework to evaluate the potential health impact of Mg fertilization for the first time. RESULTS: Compared to control, Mg fertilization increased the 2‐year average pepper yield by 25.6%, whereas there was no significant yield improvement when Mg rates exceeded 112.5 kg MgO ha−1. Magnesium application increased concentrations of Mg and capsaicinoids, decreased those of calcium (Ca), zinc (Zn) and vitamin C (Vc), and had no effect on potassium (K) and iron (Fe) in pepper fruit. As a result, Mg fertilization decreased the comprehensive nutrition level of pepper by 16.6%. Furthermore, the current health burden of the Chinese adult population associated with pepper consumption is estimated at 21.3 million DALYs per year, with the risk being increased by 5.40 DALYs for per megagram of Mg fertilizer application. Increasing health risk was mainly attributed to decreasing concentrations of Ca and Vc in pepper fruit, though the increased Mg intakes offset the impact of 1.74% to 14.4%. CONCLUSION: Magnesium fertilization significantly improved the yield but reduced nutritional quality of pepper fruit, and increased human health risks associated with consumption of pepper fruit. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Information hiding is a technique that conceals private information in a trustable carrier, making it imperceptible to unauthorised people. This technique has been used extensively for secure transmissions of multimedia, such as videos, animations, and images. This study proposes a novel Tetris‐based data hiding scheme to flexibly hide more secret messages while ensuring message security. First, an LQ × LQ square lattice Q is selected to determine the maximum embedding capacity, and then it is filled without gaps through rotating and sliding tetrominoes while making the shape of each tetromino different. Secondly, according to the decided Q, the reference matrix and corresponding look‐up table are constructed and then used for secret messages embedding and extraction. In the authors approach, each pixel pair of the original image can be processed to conceal 4‐ or 6‐bit secret messages. The experimental results show that their proposed Tetris‐based scheme has excellent performance, exceeding the performance of some state‐of‐the‐art schemes in both embedding capacity and visual quality. The proposed scheme also provides secure covert communication. [ABSTRACT FROM AUTHOR]

Memristors are a new type of circuit element with a resistance that is tunable to discrete levels by a voltage/current and sustainable after removal of power, allowing for low‐power computation and multilevel information storage. Many organic‐inorganic lead perovskites are reported to demonstrate memristive behavior, but few have been considered for use as a multilevel memory; also, their potential application has been hindered by the toxicity of lead ions. In this article, lead‐free perovskite MASnBr3 was utilized in memristors for quaternary information storage. Indium tin oxide (ITO)/MASnBr3/Au memristors were fabricated and showed reliable memristive switching with well‐separated ON/OFF states of a maxima resistance ratio of 102 to 103. More importantly, four resistive states can be distinguished and repeatedly written/read/erased with a retention time of 104 seconds and an endurance of 104 pulses. By investigating the current‐electrode area relationship, Br distribution in the ON/OFF states by in situ Raman and scanning electron microscopy, and temperature‐dependent current decay, the memristive behavior was explicitly attributed to the forming/breaking of conductive filaments caused by the migration of Br− under an electric field. In addition, poly(ethylene terephthalate)‐ITO/MASnBr3/Au devices were found to retain their multiresistance state behavior after being bent for 1000 times, thus demonstrating good device flexibility. Our results will inspire more lead‐free perovskite work for multilevel information storage, as well as other memristor‐based electronics. [ABSTRACT FROM AUTHOR]

Periplocae Cortex, named Xiang‐Jia‐Pi in China, has been widely used to treat autoimmune diseases, especially rheumatoid arthritis. However, the invivo substances of Periplocae Cortex remain unknown yet. In this study, an ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was used for profiling the chemical components and related metabolites of Periplocae Cortex. A total of 98 constituents were identified or tentatively characterized in Periplocae Cortex: 42 C21 steroidal glycosides, 10 cardiac glycosides, 23 organic acids, 4 aldehydes, 7 triterpenes, and 12 other types. Among them, 18 components were unambiguously identified by comparison with reference standards. In addition, 176 related xenobiotics (34 prototypes and 142 metabolites) were screened out and characterized in rats' biosamples (plasma, urine, bile, and feces) after the oral administration of Periplocae Cortex. Moreover, the metabolic fate of periplocoside S‐4a, a C21 steroidal glycoside, was proposed for the first time. In summary, phase II reactions (methylation, glucuronidation, and sulfation), phase I reactions (hydrolysis reactions, oxygenation, and reduction), and their combinations were the predominant metabolic reactions of Periplocae Cortex in rat. It is the first report to reveal the invivo substances and metabolism feature of Periplocae Cortex. This study also provided meaningful information for further pharmacodynamics study of Periplocae Cortex, as well as its quality control research. [ABSTRACT FROM AUTHOR]

A Cu(II)‐catalyzed ortho‐selective amination of simple phenols with O‐benzoylhydroxylamines has been developed, which provides access to 2‐aminophenols under mild conditions. Various functional groups on the phenol and electrophilic amine are compatible, and the protocol typically delivers the products in moderate to good yields. The mechanistic detail of this process are discussed. [ABSTRACT FROM AUTHOR]

Fuziline, an aminoalcohol‐diterpenoid alkaloid derived from Aconiti lateralis radix preparata, has been reported to have a cardioprotective activity in vitro. However, the potential mechanism of fuziline on myocardial protection remains unknown. In this study, we aimed to explore the efficacy and mechanism of fuziline on isoproterenol (ISO)‐induced myocardial injury in vitro and in vivo. As a result, fuziline effectively increased cell viability and alleviated ISO‐induced apoptosis. Meanwhile, fuziline significantly decreased the production of ROS, maintained mitochondrial membrane potential (MMP) and blocked the release of cytochrome C, suggesting that fuziline could play the cardioprotective role through restoring the mitochondrial function. Fuziline also could suppress ISO‐induced endoplasmic reticulum (ER) stress via the PERK/eIF2α/ATF4/Chop pathway. In addition, using ROS scavenger NAC could decrease ISO‐induced apoptosis and block ISO‐induced ER stress, while PERK inhibitor GSK2606414 did not reduce the production of ROS, indicating that excess production of ROS induced by ISO triggered ER stress. And fuziline protected against ISO‐induced myocardial injury by inhibiting ROS‐triggered ER stress. Furthermore, fuziline effectively improved cardiac function on ISO‐induced myocardial injury in rats. Western blot analysis also showed that fuziline reduced ER stress‐induced apoptosis in vivo. Above these results demonstrated that fuziline could reduce ISO‐induced myocardial injury in vitro and in vivo by inhibiting ROS‐triggered ER stress via the PERK/eIF2α/ATF4/Chop pathway. [ABSTRACT FROM AUTHOR]

Aroma is an important index of tea quality. The volatile C6‐compounds formed from linoleic and linolenic acids in tea leaf lipids are essential components of tea. C6‐compounds are formed and transformed during the postharvest process of tea leaves. However, the metabolic flux of these C6‐compounds, the activities of related enzymes, and the transcription of related genes during the postharvest process of oolong tea remain unclear. In this study, the chemical profiles of C6‐aldehydes and C6‐alcohols, the pattern of ADH enzyme activity, and the level of CsADH gene expression during the postharvest process of oolong tea were investigated. We found that the turnover process had a positive effect on the accumulation of C6‐alcohols and simultaneously induced ADH activity, especially during the withering stage. The expression of CsADH peaked during the turnover stage. The relative expression level of CSA019598 typically increased during the postharvest process. Correlation analysis demonstrated that CSA019598 expression increased as ADH activity increased. This finding suggests that CSA019598 may play a prominent role in regulating ADH. These results advance our understanding of C6‐compound formation during the postharvest process of oolong tea. We aim to evaluate how green leaf volatiles affect the enzymatic formation and genetic transcription of aromatic compounds in oolong tea in future studies. [ABSTRACT FROM AUTHOR]

Hybrid materials have obtained well‐deserved attention for energy storage devices, because they show high capacitances and high energy densities induced by the synergistic effect between complementary components. Polyoxometalate‐based metal–organic frameworks (POMOFs) possess the abundant redox‐active sites and ordered structures of polyoxometalates (POMs) and metal–organic frameworks (MOFs), respectively. Here, an asymmetric supercapacitor (ASC) NENU‐5/PPy/60//FeMo/C was fabricated in which both its electrodes are prepared from POMOF precursors. A typical POMOF material, NENU‐5, was first connected with polypyrrole (PPy) through electrodeposition to form the cathode material NENU‐5/PPy. Another representative POMOFs material, PMo12@MIL‐100, was carbonized to obtain the anode material FeMo/C. Cathode NENU‐5/PPy exhibited an extraordinary capacitance of 508.62 F g−1 (areal capacitance: 2034.51 mF cm−2). In addition, anode FeMo/C shows excellent cyclic stability attributed to its unique structure. Finally, benefiting from the outstanding capacitances and structural merits of the anode and cathode, assembled asymmetric supercapacitor NENU‐5/PPy/60//FeMo/C achieves an energy density of 1.12 mWh cm−3 at a power density output of 27.78 mW cm−3, as well as a notable life of 10 000 cycles with an capacity retention of 80.62 %. Thus, the unique ASC is strongly competitive in high capacitance, long cycle life, and high energy‐required energy storage devices. [ABSTRACT FROM AUTHOR]

Background: The increasing availability of large high‐dimensional data from experimental medicine, population‐based and clinical cohorts, clinical trials, and electronic health records has the potential to transform dementia research. Our ability to make best use of this rich data will depend on utilisation of advanced machine learning and artificial intelligence (AI) techniques and collaboration across disciplinary and geographic boundaries. Method: The Deep Dementia Phenotyping (DEMON) Network launched in 20191 to support the growing interest in machine learning and AI. Led by Director Prof David Llewellyn and Deputy Director Dr Janice Ranson, the leadership team additionally includes 5 Theme Leads and 14 Working Group Leads, supported by an international Steering Committee of world‐leading academics. Core funding is provided by Alzheimer's Research UK, the Alan Turing Institute and the University of Exeter, with additional support from strategic partners including the UK Dementia Research Institute and the Alzheimer's Society. Grand Challenges were established at a National Strategy Workshop in June 2020. Multidisciplinary Working Groups were formed to coordinate practical activities in seven key areas: Genetics and omics, experimental medicine, drug discovery and trials optimisation, biomarkers, imaging, dementia prevention, and applied models and digital health. Additional Special Interest Groups coordinate topic specific collaborations. Result: Membership on 4th February 2022 comprised 1,321 individuals from 61 countries across 6 continents (see Figure). Areas of expertise include dementia research (904; 68%), data science (692; 52%), clinical practice (244; 18%), industry (162; 12%), and regulation (26; 2%). Individual membership is free, and regular knowledge transfer events are provided including a monthly seminar series, talks and workshops, training, networking, and early career development. Each Working Group meets monthly, with multiple grants, reviews, and original research articles in progress. Eight state of the science position papers are in preparation, resulting from a Symposium held in April 2021. In January 2022, 110 early career researchers participated in the Network's flagship event 'NEUROHACK', a 4‐day competitive global hackathon, with pilot grants awarded to those generating the most innovative solutions. Conclusion: The DEMON Network is a rapidly growing global platform for innovation that is supporting the global dementia research community to collaborate. Find out more at demondementia.com [ABSTRACT FROM AUTHOR]

Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase with dual properties of an oncoprotein and an oncosuppressor in distinctive cell types. In solid cancers, two isoforms SYK(L) and SYK(S) of SYK were recently identified due to its alternative mRNA splicing. However, the cellular activity and the biological significance of the long isoform of SYK, SYK(L), is still not well defined in human lung cancers. Here, we describe an interaction between SYK(L) and the ubiquitously expressed transcription regulator Yin Yang 1 (YY1) in the nucleus, which suppresses the epithelial‐to‐mesenchymal transition (EMT) by inactivating SNAI2 (coding transcription factor SLUG) transcription. ChIP indicated that endogenous SYK(L) interacts directly with a YY1 binding cis‐regulatory element in the SNAI2 promoter. Importantly, knockdown of YY1 activates SYK(L)‐dependent EMT suppression in human lung cancer H1155 cells. We also found that the protein level of SYK(L) is markedly upregulated in various types of human lung cancers, and its nuclear localization is strongly correlated with clinical benefits of lung adenocarcinomas. Collectively, our data reveal a SYK(L)‐dependent transcriptional regulation of EMT through SLUG as a potential biomarker for lung cancer aggressiveness. An interaction between the long isoform of spleen tyrosine kinase and the ubiquitously expressed transcription regulator Yin Yang 1 suppresses the epithelial‐to‐mesenchymal transition (EMT) by inactivating SNAI2 (coding transcription factor SLUG) transcription in cancer cells. The data reveal a SYK(L)‐dependent transcriptional regulation of EMT through SLUG is needed for cancer aggressiveness. [ABSTRACT FROM AUTHOR]

Abstract: The effects of temperature on the filtration efficiency and pressure drop of a dual‐layer granular bed filter were investigated in a hot dual‐layer granular bed filter with experimental dust. Enhanced higher filtration efficiency was obtained with higher filtration temperature, and the removal efficiency of ultrafine dust was also at a high level. Simultaneously, the total pressure drop maintained at an acceptable range. The results demonstrate that the dual‐layer granular bed has excellent prospects for application to low‐temperature coal pyrolysis. [ABSTRACT FROM AUTHOR]

Abstract: Xian‐Ling‐Gu‐Bao capsule (XLGB), a well‐known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence‐based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH3). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered in the metabolism of prenylated flavonol glycosides in rat intestinal microflora. [ABSTRACT FROM AUTHOR]

Abstract: A target and nontarget strategy based on in‐house chemical components library was developed for rapid and comprehensive analysis of complicated components from traditional Chinese medicine preparation Shuang‐Huang‐Lian oral liquid. The sample was analyzed by ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry using generic acquisition parameters. Automated detection and data filtering were performed on the UNIFI™ software and the detected peaks were evaluated against an in‐house library. As a result, a total of 170 chemical components (110 target compounds and 60 nontarget ones) were identified or tentatively characterized, including 54 flavonoids, 30 phenylethanoid glycosides, 16 iridoid glycosides, 14 lignans, 32 organic acids, 19 triterpenoid saponins and five other types of compounds. Among them, 44 compounds were further confirmed by comparison with reference standards. It was demonstrated that this systematical approach could be successfully applied for rapid identification of multiple compounds in traditional Chinese medicine and its preparations. Furthermore, this work established the foundation for the further investigation on the metabolic fates of multiple ingredients in Shuang‐Huang‐Lian oral liquid. [ABSTRACT FROM AUTHOR]

In QSAR/QSPR modeling, building an accurate partial least squares (PLS) model usually involves descriptor selection, outlier detection, applicability domain assessment, nonlinear relationship, and model stability problems. In the present study, we presented an ensemble PLS (EnPLS) method for solving these modeling tasks under a unified methodology framework. EnPLS aims at developing a consistent algorithmic framework by means of the idea of ensemble learning and statistical distribution. The approach exploits the fact that the distribution of PLS model coefficients provides a mechanism for ranking and interpreting the effects of variables, whereas the distribution of prediction errors provides a mechanism for differentiating the outliers from normal samples and assessing the applicability domain of models. The use of statistics of these distributions, namely, mean/median value and standard deviation, inherently provides a feasible way to effectively describe the information contained by the original samples. Furthermore, ensemble modeling and prediction based on several cross-predictive PLS models could effectively improve the model prediction performance and increase the model stability to a certain extent. The aqueous solubility data are used to demonstrate the ability of our proposed EnPLS method in solving various modeling tasks such as descriptor selection, outlier detection, applicability domain assessment, performance improvement, and model stability. Finally, a freely available R package implementing EnPLS is developed to facilitate the use of chemists and pharmacologists. The R package is freely available at . [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections and plays a role in prostatic carcinogenesis and prostate cancer (PCa) progression. However, the mechanisms through which UPEC promotes PCa development and progression are unclear. Cytotoxic necrotizing factor 1 (CNF1) is one of the most important UPEC toxins and its role in PCa progression has never been studied. We found that UPEC-secreted CNF1 promoted the migration and invasion of PCa cells and PCa metastasis. In vitro studies showed that CNF1 promotes pro-migratory and pro-invasive activity through entering PCa cells and activating Cdc42, which subsequently induced PAK1 phosphorylation and up-regulation of MMP-9 expression. CNF1 also promoted pulmonary metastasis in a xenograft mouse model through these mechanisms. PAK1 phosphorylation correlated with advanced grades of PCa in human clinical PCa tissues. These results suggest that CNF1 derived from UPEC plays an important role in PCa progression through activating a Cdc42-PAK1 signal axis and up-regulating the expression of MMP-9. Therefore, surveillance for and treatment of cnf1-carrying UPEC strains may diminish PCa progression and thus have an important clinical therapeutic impact. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: To investigate using magnetic resonance imaging (MRI) myocardial injuries and cardiac function in patients with newly diagnosed severe primary overt hypothyroidism (HT) before and after achieving euthyroidism by short-term levothyroxine treatment. Levothyroxine treatment improves cardiovascular performance and ventricular remodeling in patients with HT, but diffuse myocardial injuries induced by HT are difficult to detect clinically.Materials and Methods: Myocardial longitudinal relaxation time (T1 ) mapping using the modified Look-Locker inversion-recovery (MOLLI) sequences at 3.0T was performed before and after euthyroidism was achieved by levothyroxine treatment in 24 patients with Hashimoto's thyroiditis, and compared to 17 healthy controls. Subjects underwent measurements of T1 values and left ventricular stroke volume (SV), ejection fraction (EF), cardiac index (CI), and peak filling rate (PFR). Cardiac data were expressed as an index, as per body surface area, except for heart rate and EF.Results: Patients with untreated HT exhibited significantly longer native myocardial T1 values (all P < 0.05) accompanied by reduced SV (30.7 ± 5.6 vs. 34.9 ± 6.8 mL/m2 , P < 0.05), CI (2.1 ± 0.4 vs. 2.4 ± 0.4 L/min/m2 , P < 0.05), and PFR (3.5 ± 0.9 vs. 4.2 ± 1.1 EDV/s, P < 0.05) compared to healthy controls at baseline. Achieving euthyroidism resulted in a significant decrease in T1 values and improved SV, CI, and PFR values (all P < 0.05) in the patients with HT. Negative correlations of the T1 values with free triiodothyronine (r = -0.55, P < 0.001) and PFR (r = -0.46, P = 0.0016) were observed.Conclusion: We suggest that the negative effect induced by severe overt HT on the cardiovascular system can be significantly improved by restoring euthyroidism with short-term levothyroxine therapy.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:897-904. [ABSTRACT FROM AUTHOR]

Hepatitis C virus ( HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/M φ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the role of transcription factor, T-box expressed in T cells (T-bet), in Tim-3 expression in M/M φ in the setting of HCV infection. We demonstrate that T-bet is constitutively expressed in resting CD14+ M/M φ in the peripheral blood. M/M φ from chronically HCV-infected individuals exhibit a significant increase in T-bet expression that positively correlates with an increased level of Tim-3 expression. Up-regulation of T-bet is also observed in CD14+ M/M φ incubated with HCV+ Huh7.5 cells, as well as in primary M/M φ or monocytic THP-1 cells exposed to HCV core protein in vitro, which is reversible by blocking HCV core/ gC1qR interactions. Moreover, the HCV core-induced up-regulation of T-bet and Tim-3 expression in M/M φ can be abrogated by incubating the cells with SP600125 - an inhibitor for the c-Jun N-terminal kinase ( JNK) signalling pathway. Importantly, silencing T-bet gene expression decreases Tim-3 expression and enhances interleukin-12 secretion as well as signal transducer and activator of transcription 1 phosphorylation. These data suggest that T-bet, induced by the HCV core/ gC1qR interaction, enhances Tim-3 expression via the JNK pathway, leading to dampened M/M φ function during HCV infection. These findings reveal a novel mechanism for Tim-3 regulation via T-bet during HCV infection, providing new targets to combat this global epidemic viral disease. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells ( MDSCs) and micro RNAs (mi RNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus ( HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Treg cells is regulated by an mi RNA-mediated mechanism. The RNA array analysis revealed that six mi RNAs were up-regulated and six mi RNAs were down-regulated significantly in myeloid cells during HCV infection. Real-time RT- PCR confirmed the down-regulation of miR-124 in MDSCs from HCV patients. Bioinformatic analysis suggested that miR-124 may be involved in the regulation of signal transducer and activator of transcription 3 ( STAT-3), which was overexpressed in MDSCs from HCV patients. Notably, silencing of STAT-3 significantly increased the miR-124 expression, whereas reconstituting miR-124 decreased the levels of STAT-3, as well as interleukin-10 and transforming growth factor- β, which were overexpressed in MDCSs, and reduced the frequencies of Foxp3+ Treg cells that were developed during chronic HCV infection. These results suggest that reciprocal regulation of miR-124 and STAT-3 in MDSCs promotes Treg cell development, thus uncovering a novel mechanism for the expansion of MDSC and Treg cells during HCV infection. [ABSTRACT FROM AUTHOR]