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Summary: Background and Aims: We aimed to define gender‐specific, optimal alanine aminotransferase (ALT) cut‐off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. Methods: In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut‐off values. Area under the curve (AUC) values were calculated to assess their predictive performance. Results: A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut‐off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut‐off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut‐off values were greater than those of the current recommendations. Conclusion: This study established novel optimal ALT cut‐off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy. [ABSTRACT FROM AUTHOR]

Background: Treating postherpetic neuralgia (PHN), which is characterized with a long‐lasting lancinating mechanical allodynia or hyperalgesia, is a big challenge as it is hard to achieve complete resolution. A synthetic triterpenoid, CDDO (2‐cyano‐3,12‐dioxoolean‐1,9‐dien‐28‐oic acid) can exert pleiotropic effects including anti‐inflammation and neuroprotective activities. Nevertheless, the antinociceptive effect of CDDO and its derivatives remains unknown. Resiniferatoxin (RTX) is easily feasible, and an RTX‐treated rodent model can mimic the PHN‐like symptoms. Therefore, RTX‐treated rats were used to serve as a PHN rats' model in the study to elucidate whether a synthetic triterpenoid, CDDO, can improve mechanical allodynia in RTX‐treated rats. Methods: The antinociceptive effects of CDDO were assessed by behavioral tests, western blotting, and immunohistochemistry. Paw withdrawal mechanical threshold was determined using calibrated forceps. Results: Administration of RTX led to mechanical allodynia, neuronal cell death, and glial cell activation in the spinal cord of RTX‐treated rats. A synthetic triterpenoid, CDDO, blocked RTX‐induced mechanical allodynia, rescued neuronal cell death, and inhibited glial cell activation in the spinal cord of RTX‐treated rats. Conclusions: Our study provides a novel result that a synthetic triterpenoid, CDDO, can interfere neuronal cell death and glial cell activation in the spinal cord of RTX‐treated rats. Hence, CDDO is an alternative therapeutic choice for PHN. [ABSTRACT FROM AUTHOR]

(1 − x)Bi0.5Na0.47Li0.03Ti0.99Sn0.01O3–xSrTiO3 (BNLST–xST) lead‐free ceramics were synthesized by traditional solid phase sintering. When x = 0.4, the ceramic achieves a high energy storage density Wrec of 3.78 J/cm3 as well as a superior efficiency η of 90.3% under 360 kV/cm. The charge–discharge curves related to temperature and cycle show that the 0.6BNLST–0.4ST sample has good temperature stability (20–180°C) and cycling reliability (variation of WD < 5%). Moreover, a fast discharge rate (t0.9 = 0.219 μs) and a large discharge energy density (WD = 1.89 J/cm3) are achieved at 220 kV/cm. The results show that BNLST–xST energy storage ceramics are promising materials for devices with pulsed power capacitor. [ABSTRACT FROM AUTHOR]

Aim: Timely recruitment of eligible participants is essential for the success of clinical trials, with insufficient accrual being the leading cause for premature termination of both oncology and non‐oncology trials. Methods: In this paper we further elaborate on the challenges for patient participation in oncology trials from physician, patient, healthcare system, and some trial‐related perspectives. Results: We present strategies such as use of digital healthcare technologies, real‐world data and real‐world evidence, decentralized clinical trials, pragmatic trial designs, and supportive services to increase patient participation. Conclusions: Multifaceted measures are necessary to increase patient participation, especially for those who are under‐represented in cancer trials. [ABSTRACT FROM AUTHOR]

Background and purpose: Multiple system atrophy (MSA) has no definitive genetic or environmental (G‐E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G‐E factors associated with MSA and its subtypes, MSA‐P and MSA‐C. Methods: A consecutive case–control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model. Results: A total of 207 MSA patients and 136 healthy controls were enrolled. In addition to SNP COQ2_rs148156462 (TT), MSA risk was correlated with G‐E interactions, including COQ2_rs148156462 (Tc) × pesticide nonexposure, COQ2_rs148156462 (TT) × current smokers, SNCA_rs11931074 (tt) × alcohol nonusers, and SNCA_rs11931074 (GG) × well water nondrinkers (all p < 0.01), with an area under the receiver operating characteristic curve (AUC) of 0.804 (95% confidence interval [CI] = 0.671–0.847). Modulated risk of MSA‐C, with MSA‐P as a control, correlated with COQ2_rs148156462 (TT) × alcohol nondrinkers, SNCA_rs11931074 (GG) × well water ever drinkers, SNCA_rs11931074 (Gt) × well water never drinkers, and SNCA_rs3857059 (gg) × pesticide nonexposure (all p < 0.05), with an AUC of 0.749 (95% CI = 0.683–0.815). Conclusions: Certain COQ2 and SNCA SNPs interact with common environmental factors to modulate MSA etiology and subtype disposition. The mechanisms underlying the observed correlation between G‐E interactions and MSA etiopathogenesis warrant further investigation. [ABSTRACT FROM AUTHOR]

Morphological edge detection is a principal component in pattern recognition and machine vision. Traditional edge detection operators only take pixel mutual into consideration. However, the edges are influenced not only by pixel mutual but also by the boundary characteristics. Here, the vector co‐occurrence morphological edge detection operator is proposed, which takes the pixel and boundary information both into consideration. The vector co‐occurrence algorithm is exploited to resist the influence of the noise points and detect the edges from the colour image rather than the grey image. And, we lead to define a precise definition of the manner of sorting high‐dimensional data for the colour image. The experiment results always illustrate the advancement and practicability of our methods against the baseline method. In terms of experiments, the BSDS500 dataset is introduced to compare and analyse with other algorithms. Based on the standard benchmark index evaluation in the BSDS500 dataset, the ODS and AP of various algorithms are compared and analysed. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the clinical outcomes of the Wiltse approach and percutaneous pedicle screw placement under O‐arm navigation for the treatment of thoracolumbar fracture. Methods: We enrolled a total of 54 patients with neurologically intact thoracolumbar fracture who received minimally invasive treatments between October 2014 and October 2018 in this retrospective study. Among these, 28 patients (22 males and six females, with a mean age of 48.6 ± 9.6 years) were treated with pedicle screw fixation through the Wiltse approach (WPSF), and another 26 (15 males and 11 females, with a mean age of 45.7 ± 10.6 years) received percutaneous pedicle screw fixation under O‐arm navigation (OPSF). Statistical methods were used to perform a detailed comparison of clinical outcomes, radiologic findings, and complications between the two groups obtained preoperatively, postoperatively, and at last follow‐up. Results: All patients underwent surgery successfully and finished a follow‐up of more than 12 months. No serious complications, such as infection, blood vessel injury, or spinal cord or nerve root injury occurred. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, local Cobb angle (LCA), vertebral wedge angle (VWA), and R value were notably improved after surgery, though there was no clear discrepancy between the groups at each time point (P > 0.05). During the follow‐up period, no patients developed neurological impairment or implant‐related complications, and no patients underwent revision surgery. The WPSF group had a significantly shorter operation time than the OPSF group (68.1 ± 9.8 vs 76.1 ± 9.0 minutes, P = 0.005). Moreover, the WPSF group showed less cost of surgery than the WPSF group (48142.1 ± 1430.1 vs 59035.4 ± 1152.7 CNY, P < 0.001). There were no significant differences between the two groups in terms of the intraoperative bleeding, length of incision, or postoperative hospitalization time (P > 0.05). The accuracy of pedicle screw placement was 95.2% (160/168) in the WPSF group and 96.8% (151/156) in the OPSF group, with no significant difference between the groups (P = 0.432). Conclusion: Both WPSF and OPSF were safe and effective for the treatment of thoracolumbar fracture. Although the two groups showed favorable clinical and radiologic outcomes through to final follow‐up, we recommended the minimally invasive WPSF given its shorter operation time and lower cost of surgery. [ABSTRACT FROM AUTHOR]

Abstract: A volatility diagram of zirconium carbide (ZrC) at 1600, 1930, and 2200°C was calculated in this work. Combining it with the existing volatility diagrams of ZrB2 and SiC, the volatility diagram of a ternary ZrB2‐SiC‐ZrC (ZSZ) system was constructed in order to interpret the oxidation behavior of ZSZ ceramics. Applying this diagram, the formation of ZrC‐corroded and SiC‐depleted layers and the oxidation sequence of each component in ZSZ during oxidation and ablation could be well understood. Most of the predictions from the diagrams are consistent with the experimental observations on the oxidation scale of dense ZrB2‐SiC‐ZrC ceramics/coatings after oxidation at 1600°C or ablation at 1930 and 2200°C. The reasons for the discrepancy are also briefly discussed. [ABSTRACT FROM AUTHOR]

Aims: Our study focused on exploring the feasible prognostic laboratory parameters of HCC and establishing a score model to estimate individualized overall survival (OS) in HCC after resection. Methods: Four hundred and sixty‐one patients with HCC who underwent hepatectomy between January 2010 and December 2017 was enrolled in this investigation. Cox proportional hazards model was conducted to analyze the prognostic value of laboratory parameters. The score model construction was based on the forest plot results. Overall survival was evaluated by Kaplan‐Meier method and the log‐rank test. The novel score model was validated in an external validation cohort from a different medical institution. Results: We identified that alpha fetoprotein (AFP), total bilirubin (TB), fibrinogen (FIB), albumin (ALB), and lymphocyte (LY) were independent prognostic factors. High AFP, TB, FIB (HR > 1, p < 0.05), and low ALB, LY (HR < 1, p < 0.05) were associated with the survival of HCC. The novel score model of OS based on these five independent prognostic factors achieved high C‐index of 0.773 (95% confidence interval [CI]: 0.738–0.808), which was significantly higher than those of the single five independent factors (0.572–0.738). The score model was validated in the external cohort whose C‐index was 0.7268 (95% CI: 0.6744–0.7792). Conclusion: The novel score model we established was an easy‐to‐use tool which could enable individualized estimation of OS in patients with HCC who underwent curative hepatectomy. [ABSTRACT FROM AUTHOR]

SUMMARY: Hydrogen sulfide (H2S) promotes plant tolerance against various environmental cues, and d‐cysteine desulfhydrase (DCD) is an enzymatic source of H2S to enhance abiotic stress resistance. However, the role of DCD‐mediated H2S production in root growth under abiotic stress remains to be further elucidated. Here, we report that DCD‐mediated H2S production alleviates osmotic stress‐mediated root growth inhibition by promoting auxin homeostasis. Osmotic stress up‐regulated DCD gene transcript and DCD protein levels and thus H2S production in roots. When subjected to osmotic stress, a dcd mutant showed more severe root growth inhibition, whereas the transgenic lines DCDox overexpressing DCD exhibited less sensitivity to osmotic stress in terms of longer root compared to the wild‐type. Moreover, osmotic stress inhibited root growth through repressing auxin signaling, whereas H2S treatment significantly alleviated osmotic stress‐mediated inhibition of auxin. Under osmotic stress, auxin accumulation was increased in DCDox but decreased in dcd mutant. H2S promoted auxin biosynthesis gene expression and auxin efflux carrier PIN‐FORMED 1 (PIN1) protein level under osmotic stress. Taken together, our results reveal that mannitol‐induced DCD and H2S in roots promote auxin homeostasis, contributing to alleviating the inhibition of root growth under osmotic stress. Significance Statement: Hydrogen sulfide (H2S) promotes plant tolerance against various environmental stress resistance. However, the role of H2S in root development under abiotic stress remains to be further elucidated. Here, we report that d‐cysteine desulfhydrase‐mediated H2S accumulation alleviates root growth inhibition under osmotic stress by promoting auxin homeostasis. [ABSTRACT FROM AUTHOR]

Perovskite single crystals have attracted tremendous attention owing to their excellent optoelectronic properties and stability compared to typical multicrystal structures. However, the growth of high‐quality perovskite single crystals (PSCs) generally relies on temperature gradients or the introduction of additives to promote crystal growth. In this study, a vacuum evaporation crystallization technique is developed that allows PSCs to be grown under extremely stable conditions at constant temperature and without requiring additives to promote crystal growth. The new method enables the growth of PSCs of unprecedented quality, that is, MAPbBr3 single crystals that exhibit an ultranarrow full width at half maximum of 0.00701°, which surpasses that of all previously reported values. In addition, the MAPbBr3 single crystals deliver exceptional optoelectronic performance, including a long carrier lifetime of 1006 ns, an ultralow trap‐state density of 3.67 × 109 cm−3, and an ultrahigh carrier mobility of 185.86 cm2 V−1 s−1. This method is applicable to various types of PSCs, including organic–inorganic hybrids, fully inorganic structures, and low‐dimensional structures. [ABSTRACT FROM AUTHOR]

Micro‐Doppler effect is a vital feature of a target that reflects its oscillatory motions apart from bulk motion and provides an important evidence for target recognition with radars. However, establishing the micro‐Doppler database poses a great challenge, since plenty of experiments are required to get the micro‐Doppler signatures of different targets for the purpose of analyses and interpretations with radars, which are dramatically limited by high cost and time‐consuming. Aiming to overcome these limits, a low‐cost and powerful simulation platform of the micro‐Doppler effects is proposed based on time‐domain digital coding metasurface (TDCM). Owing to the outstanding capabilities of TDCM in generating and manipulating nonlinear harmonics during wave‐matter interactions, it enables to supply rich and high‐precision electromagnetic signals with multiple micro‐Doppler frequencies to describe the micro‐motions of different objects, which are especially favored for the training of artificial intelligence algorithms in automatic target recognition and benefit a host of applications like imaging and biosensing. [ABSTRACT FROM AUTHOR]

Rates of ecosystem processes such as decomposition are likely to change as a result of human impacts on the environment. In southern California, climate change and nitrogen (N) deposition in particular may alter biological communities and ecosystem processes. These drivers may affect decomposition directly, through changes in abiotic conditions, and indirectly through changes in plant and decomposer communities. To assess indirect effects on litter decomposition, we reciprocally transplanted microbial communities and plant litter among control and treatment plots (either drought or N addition) in a grassland ecosystem. We hypothesized that drought would reduce decomposition rates through moisture limitation of decomposers and reductions in plant litter quality before and during decomposition. In contrast, we predicted that N deposition would stimulate decomposition by relieving N limitation of decomposers and improving plant litter quality. We also hypothesized that adaptive mechanisms would allow microbes to decompose litter more effectively in their native plot and litter environments. Consistent with our first hypothesis, we found that drought treatment reduced litter mass loss from 20.9% to 15.3% after six months. There was a similar decline in mass loss of litter inoculated with microbes transplanted from the drought treatment, suggesting a legacy effect of drought driven by declines in microbial abundance and possible changes in microbial community composition. Bacterial cell densities were up to 86% lower in drought plots and at least 50% lower on litter derived from the drought treatment, whereas fungal hyphal lengths increased by 13-14% in the drought treatment. Nitrogen effects on decomposition rates and microbial abundances were weaker than drought effects, although N addition significantly altered initial plant litter chemistry and litter chemistry during decomposition. However, we did find support for microbial adaptation to N addition with N-derived microbes facilitating greater mass loss in N plots than in control plots. Our results show that environmental changes can affect rates of ecosystem processes directly through abiotic changes and indirectly through microbial abundances and communities. Therefore models of ecosystem response to global change may need to represent microbial biomass and community composition to make accurate predictions. [ABSTRACT FROM AUTHOR]

Abstract: The C-Jun N-terminal Kinase (JNK) inhibitor SP600125 is widely used to inhibit the JNK-mediated Bax activation and cell apoptosis. However, this report demonstrates that SP600125 synergistically enhances the dihydroartemisinin (DHA)-induced human lung adenocarcinoma cell apoptosis by accelerating Bax translocation and subsequent intrinsic apoptotic pathway involving mitochondrial membrane depolarization, cytochrome c release, caspase-9 and caspase-3 activation. The dynamical analysis of GFP-Bax mobility inside single living cells using fluorescence recovery after photobleaching revealed that SP600125 aggravated the DHA-induced decrease of Bax mobility and Bax translocation. These results for the first time present a novel pro-apoptotic action of SP600125 in DHA-induced apoptosis. [ABSTRACT FROM AUTHOR]

A surface plasmon resonance (SPR) sensor based on hollow‐core photonic crystal fibre (HC‐PCF) filled with silver nanowires is designed. The analyte and silver nanowires are full filled in the air holes of the HC‐PCF to realise the SPR sensing, which is more convenient than silver coated in operation. The designed sensor is analysed through numerical simulations and demonstrated by experiments. All the results show that a blue‐shift is obtained with increase of the analyte refractive index (RI), and the silver nanowires concentration has no effect on spectral sensitivity. The highest average spectral sensitivity of 14 240 nm/RIU is obtained by experiments, which is higher than that previously reported for the same type of sensors. The sensor is useful for detecting small analyte RI changes, and can also provide a reference for the implementation and application of PCF‐SPR sensors with high sensitivity. [ABSTRACT FROM AUTHOR]

The transcriptional regulation of membrane fatty acid composition in the human pathogen Streptococcus pneumoniae is distinct from the systems utilized in the model organisms Escherichia coli and Bacillus subtilis. The genes encoding the components of type II fatty acid biosynthesis cluster at a single location within the S. pneumoniae genome, and the second gene in this cluster (SPR0376) encodes a transcription factor (FabT) that belongs to the MarR superfamily. Derivatives of S. pneumoniae strain D39 were constructed that lacked functional FabT. This strain had significantly elevated levels of saturated fatty acids and longer chain lengths than the control strain, was unable to grow at pH 5.5 and had increased sensitivity to detergent. Eliminating FabT function increased the expression levels of all of fab genes with the notable exception of fabM. FabT was purified and bound to the DNA palindrome located within the promoter regions of the fabT and fabK genes within the cluster. The analysis of cells with increased expression of individual genes leads to a model where the physical properties of the S. pneumoniae membrane is controlled primarily by the activity of FabK, the enoyl reductase, which diverts intermediates to saturated fatty acid formation, in contrast to E. coli where FabB, an elongation condensing enzyme, pulls the pathway in the direction of unsaturated acid synthesis. [ABSTRACT FROM AUTHOR]

The synaptic vesicle protein synaptotagmin I has been proposed to serve as a Ca2+ sensor for rapid exocytosis. In the present work, two fragments of the large cytoplasmic domain of synaptotagmin I, C2A and C2AB, were compared by combining surface plasmon resonance with circular dichroism and fluorescence techniques. C2AB and C2A had almost identical membrane binding constants, indicating that C2A is the predominate domain to bind to negatively charged phospholipids. After reacting with inositol hexakisphosphate (InsP6) a conformational change of C2AB was detected in the presence of liposome. The InsP6 binding notably weakened the Ca2+-dependent C2AB-membrane interaction, which suggests that InsP6 may act as a modulator of neurotransmitter release by altering the state of synaptotagmin–phospholipid interaction. [Copyright &y& Elsevier]

Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment. Extracellular vesicles (EVs) are promising nanotherapeutic agents against ALI. Herein, endothelium‐derived engineered extracellular vesicles (eEVs) that deliver microRNA‐125b‐5p (miRNA‐125b) to lung tissues exerting a protective effect on endothelial barrier integrity are reported. eEVs that are modified with lung microvascular endothelial cell‐targeting peptides (LET) exhibit a prolonged retention time in lung tissues and targeted lung microvascular endothelial cells in vivo and in vitro. To improve the efficacy of the EVs, miRNA‐125b is loaded into EVs. Finally, LET‐EVs‐miRNA‐125b is constructed. The results show that compared to the EVs, miRNA‐125b, and EVs‐miRNA‐125b, LET‐EVs‐miRNA‐125b exhibit the most significant treatment efficacy in ALI. Moreover, LET‐EVs‐miRNA‐125b is found to have an important protective effect on endothelial barrier integrity by inhibiting cell apoptosis, promoting angiogenesis, and protecting intercellular junctions. Sequencing analysis reveals that LET‐EVs‐miRNA‐125b downregulates early growth response‐1 (EGR1) levels, which may be a potential mechanism of action. Taken together, these findings suggest that LET‐EVs‐miRNA‐125b can treat ALI by protecting the endothelial barrier integrity. [ABSTRACT FROM AUTHOR]

The Taiwan Photon Source (TPS) with high brightness and energy tunability is suitable for applications in spectroscopy. The tender X‐ray absorption beamline will be optimized for X‐ray absorption spectroscopy measurements using a bending‐magnet source in a unique photon energy range (1.7–10 keV) and two crystal pairs [InSb(111) and Si(111)] separated using back‐to‐back double‐crystal monochromators (DCMs). InSb crystals are typically used in the lower photon energy range of 1.7–3.5 keV. However, the poor thermal conductivity of InSb crystals leads to severe deformation. This factor should be considered when the monochromator is installed on a tender X‐ray beamline in a storage ring with a high power density. There are many approaches to reducing the thermal load on the first crystal of a DCM. Double‐bounce high harmonics rejection mirrors in front of the DCM serve not only to reduce the high‐order harmonics but also to absorb considerable quantities of heat. Two coating stripes on the silicon surfaces with a variable incident angle will be key to solving the thermal load on this beamline. [ABSTRACT FROM AUTHOR]

The multi‐mode pain‐perceptual system (MMPPS) is essential for the human body to perceive noxious stimuli in all circumstances and make an appropriate reaction. Based on the central sensitization mechanism, the MMPPS can switch between different working modes and thus offers a smarter protection mechanism to human body. Accordingly, before injury MMPPS can offer warning of excessive pressure with normal pressure threshold. After injury, extra care on the periphery of damage will be activated by decreasing the pressure threshold. Furthermore, the MMPPS will gradually recover back to a normal state as damage heals. Although current devices can realize basic functions like damage localization and nociceptor signal imitating, the development of a human‐like MMPPS is still a great challenge. Here, a bio‐inspired MMPPS is developed for prosthetics protection, in which all working modes is realized and controlled by mimicking the central sensitization mechanism. Accordingly, the system warns one of a potential injury, identifies the damaged area, and subsequently offers extra care. The proposed system can open new avenues for designing next‐generation prosthetics, especially make other smart sensing systems operate under complete protection against injuries. [ABSTRACT FROM AUTHOR]

The multi‐mode pain‐perceptual system (MMPPS) is essential for the human body to perceive noxious stimuli in all circumstances and make an appropriate reaction. Based on the central sensitization mechanism, the MMPPS can switch between different working modes and thus offers a smarter protection mechanism to human body. Accordingly, before injury MMPPS can offer warning of excessive pressure with normal pressure threshold. After injury, extra care on the periphery of damage will be activated by decreasing the pressure threshold. Furthermore, the MMPPS will gradually recover back to a normal state as damage heals. Although current devices can realize basic functions like damage localization and nociceptor signal imitating, the development of a human‐like MMPPS is still a great challenge. Here, a bio‐inspired MMPPS is developed for prosthetics protection, in which all working modes is realized and controlled by mimicking the central sensitization mechanism. Accordingly, the system warns one of a potential injury, identifies the damaged area, and subsequently offers extra care. The proposed system can open new avenues for designing next‐generation prosthetics, especially make other smart sensing systems operate under complete protection against injuries. [ABSTRACT FROM AUTHOR]

Background: Little was known on infection and mortality rates, still less the risk factors of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) omicron variant in B‐cell lymphoma patients following CD19 targeted chimeric antigen receptor T cell (CAR‐T). Aims: We performed a retrospective multicenter study and analyzed the details of relapsed/refractory (R/R) B‐cell lymphoma patients who received CD19 targeted CAR‐T heretofore in five cellular immunotherapy centers in China during the omicron wave. Materials & Methods: One hundred fifty‐four patients were enrolled in this study. Results: Among them, 52 patients (33.8%) were uninfected, 74 patients (48.1) had ambulatory mild disease (including nine patients of asymptomatic infection), 22 patients (14.3%) had moderate disease and six patients (3.9%) had severe disease when data collected up. Three patients with severe disease died from COVID‐19, the death rate was 1.9% for all enrolled patients, and 2.9% for infected patients. We also found that patients over 60 years old or with diabetes mellitus (DM) tend to develop severe disease (p = 0.0057 and p = 0.0497, respectively). Patients had CAR‐T infusion within 6 months also tend to have severe disease (p = 0.0011). In multivariate logistic regression model, CAR‐T infusion within 6 months (relative risk (RR) 40.92; confidence interval (CI) 4.03–415.89; p = 0.002) were associated with significantly higher risk of severe disease. Conclusion: Through this study, we conclude that the outcome for B‐cell lymphoma patients following CD19 targeted CAR‐T therapy when facing omicron infection was improved, but aggressive precautionary measures were particularly crucial for patients with high risk factors. [ABSTRACT FROM AUTHOR]

Cavitation‐induced stress whitening in semi‐crystalline polymers during stretching significantly influences the physical properties of the materials. This review summarizes studies focusing on two different cavitation processes triggered at small and large strain regimes. The corresponding mechanisms of these two cavitation processes are discussed. For cavitation activated at small strain, there are two basic but distinctly different models with the initiation of cavities either in the amorphous phase or in the crystalline skeleton. For the cavitation triggered at a large strain regime, there are also two different arguments being either due to the defects located in the ends of micro‐fibrils or as a consequence of the fragmentation of load‐bearing inter‐fibril/micro‐fibril tie chains in highly oriented amorphous networks. A unified understanding of the cavitation processes during stretching semi‐crystalline polymers based on interpenetrated network model is proposed. Finally, this review outlooks future research topics for better understanding the cavitation mechanism to meet the industrial need. Stress whitening in polymers during stretching is considered to be a result of cavitation in the system. This review highlights two different cavitation processes triggered at distinct strain regimes. The cavitation around the yield point usually continues to large strains without causing catastrophic breakage of the material while the large strain cavitation ends up with polymer failure soon after activation. [ABSTRACT FROM AUTHOR]

Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non‐muscle‐invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta‐analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette‐Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random‐effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty‐seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta‐analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta‐regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias. [ABSTRACT FROM AUTHOR]

Obesity is characterized by chronic inflammation, insulin resistance, and gut microbiota dysbiosis. Dioscorea opposita Thunb. is a traditional food and medicine homolog from China. In the present study, polysaccharides isolated from a water extract of Dioscorea opposita Thunb. (DOTPs) were prepared. We showed that DOTPs reduced body weight, accumulation of fat tissues, insulin resistance, and inflammation in high‐fat diet (HFD)‐fed mice. Further experiments showed that DOTPs could regulate the composition of the gut microbiota in HFD mice. DOTPs supplementation in HFD‐fed mice resulted in the reduction of the Firmicutes‐to‐Bacteroidetes ratio. We further demonstrated that DOTPs supplementation enhanced bacterial levels of Akkermansia and reduced levels of Ruminiclostridium_9. A significant reduction of glycolysis metabolism related to obesity and gut microbiota dysbiosis was also observed upon administration of DOTPs. Our results suggest that DOTPs can produce significant anti‐obesity effects, by inhibiting systematic inflammation and ameliorating gut microbiota dysbiosis in diet‐induced obese mice. [ABSTRACT FROM AUTHOR]

Post‐laser in situ keratomileusis (post‐LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high‐fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross‐linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long‐term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide. [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]

Background: Identifying therapeutic targets and prognostic biomarkers significantly contributes to individualized treatment of acute myeloid leukemia (AML). Dihydropyrimidinase‐like 2 (DPYSL2) expression was decreased in homoharringtonine (HHT)‐resistant AML cells, which were established by our group. DPYSL2 plays an important role in axon growth and has oncogene effect in glioblastoma. However, little research has been conducted to investigate the function of DPYSL2 in AML pathogenesis. Methods: Auto‐docking was used to reveal the targeting relationship between HHT and DPYSL2. Overall survival (OS), event‐free survival (EFS), and relapse‐free survival (RFS) were used to evaluate the prognostic impact of DPYSL2 for AML. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. In vivo growth and survival were assessed using a xenotransplantation mice model. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML and were confirmed by Western blot. Results: We found DPYSL2 was the target of HHT. Next, we found AML cell lines and patients had higher DPYSL2 expression levels than the normal samples. Further multivariate analysis demonstrated that high DPYSL2 expression was an independent poor prognostic factor for OS, EFS, and RFS in AML. Inhibition of DPYSL2 expression suppressed cell growth, induced apoptosis in AML cell lines, and prolonged the survival of AML xenograft NCG mice. Through RNA‐seq analysis from TCGA and our data, the JAK2/STAT3/STAT5‐PI3K P85/AKT/GSK3b axis was thought to be the critical pathway in regulating DPYSL2 in AML development. Conclusions: We first time confirmed that DPYSL2 was a target of HHT and played an oncogene role in AML by regulating JAK/STAT signaling pathway. Therefore, DPYSL2 could serve as a novel prognostic marker and therapeutic target for AML treatment. [ABSTRACT FROM AUTHOR]

Multidecadal sea surface temperature covariance in the southern Atlantic and Indian Oceans within the 20°–45°S band (termed the SAIOs) has been detected, but the origins of these variations remain uncertain. This study focuses on the decade‐long warming surge (0.43°C/decade) during 1965–1975 and the stalled warming pace (0.05°C/decade) thereafter. Observations and models overall suggest the essence of external forcing in controlling the warming rates of these two periods. Specifically, the 1963 eruption of Mount Agung caused an abrupt cooling of the SAIO, and the recovery of radiative heating during the following decade led to rapid surface warming. The persistent positive trend of the Southern Annular Mode since the late‐1970s has retarded the SAIO warming, primarily by enhancing surface wind speed and latent heat release. Although internal variability can also affect the SAIO through atmospheric teleconnections, its role is overall secondary during the two periods. Plain Language Summary: Sea surface temperatures (SSTs) in the southern Atlantic and Indian Oceans (SAIOs) show prominent decade‐to‐decade variations, with notable impacts on global and regional climates. However, the origins of these multidecadal variations are largely unknown. While previous studies overall stressed internal climate variability, this study suggests essential effects of external drivers on the rapid warming of 1965–1975 and the subsequent slowdown. Specifically, atmospheric aerosols from the 1963 eruption of Mount Agung caused an abrupt drop in surface solar radiation, and the recovery of solar heating in the following decade led to accelerated surface warming in the SAIO. Since the late 1970s, the human‐induced Antarctic ozone hole drove a positive trend in the Southern Annular Mode. This trend enhanced the surface winds over the SAIO and attenuated the SST warming. In addition, impacts from internal variability, such as the Interdecadal Pacific Variability, are also considerable during the two periods. Key Points: The sea surface temperature (SST) warming rate of the southern Atlantic and Indian Ocean (SAIO) shows multidecadal variations, with a short‐term surge during 1965–1975 and decelerated warming thereafterThe 1963 eruption caused a dip in the SAIO SST, and the subsequent dissipation of volcanic aerosols led to accelerated warming of 1965–1975The Interdecadal Pacific Variability and Southern Annular Mode also modulate the warming rate of the SAIO through their signatures in atmospheric circulation [ABSTRACT FROM AUTHOR]

Abstract: Young and elderly breast cancer patients are more likely to have a poorer outcome than middle‐aged patients. The intrinsic molecular features for this disparity are unclear. We obtained data from the Cancer Genome Atlas (TCGA) on May 15, 2017 to test the potential mediation effects of the molecular features on the association between age and prognosis with a four‐step approach. The relative contributions of the molecular features (PAM50 subtype, risk stratification, DNAm age, and mutations in TP53, PIK3CA, MLL3, CDH1, GATA3, and MAP3K1) to age disparities in survival were estimated by Cox proportional hazard models with or without the features. Young patients were significantly more likely to have basal‐like subtype, GATA3 mutations, and younger DNA methylation (DNAm) age than middle‐aged patients (P < .05). Both the young and elderly patients had a significantly increased risk of breast cancer recurrence after adjusted by race, tumor size, and node status (Hazard ratio [HR] (95% confidence interval [CI]): 2.81 [1.44, 5.45], 2.37 [1.45, 3.89], respectively). This increased risk was weakened in the young patients after further adjustments in the molecular features, particularly basal‐like subtype, GATA3 mutations, and DNAm age (HR [95%CI]: 1.87 [0.81, 4.32]), resulting in 33.5% decreased risk of recurrence. Meanwhile, the adjustments of the molecular features did not alter the recurrence risk for the elderly patients. Compared with middle‐aged patients of breast cancer, poorer prognosis of elderly patients may be caused by aging, while poorer prognosis of young patients was probably mediated through intrinsic characteristics, such as basal‐like subtype, GATA3 mutations, and DNAm age of the cancerous tissues. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS), a multifactorial and polygenic disease, is the most common cause of death. This study aimed to determine the roles of MMP8/MMP10 polymorphisms in IS susceptibility in the Chinese Han population. Methods: MMP8 rs1940475 and rs3765620, and MMP10 rs17860949 from 700 IS patients and 700 controls were genotyped by the MassARRAY iPLEX platform. The impact of polymorphisms on IS risk was evaluated by logistic regression analysis. Results: Our study indicated that rs17860949 in MMP10 was significantly associated with a reduced risk of IS (OR = 0.632, p =.002). Precisely, stratification analysis showed that rs17860949 was relate to a decreased susceptibility to IS in patients aged > 55 years (OR = 0.472, p <.001), males (OR = 0.632, p =.012), nonsmokers (OR = 0.610, p =.017), and nondrinkers (OR = 0.559, p =.006). All these significant findings were verified by false‐positive report probability test. Furthermore, GG genotype and AG genotype in MMP8 rs3765620 polymorphism were related to a reduced triglycerides concentration (p =.018). Conclusion: Our study suggests that rs17860949 in MMP10 may play a protective role in IS in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase (Cdk) both promotes mitotic entry (spindle assembly and anaphase) and inhibits mitotic exit (spindle disassembly and cytokinesis), leading to an elegant quantitative hypothesis that a single cyclin oscillation can function as a ratchet to order these events. This ratchet is at the core of a published ODE model for the yeast cell cycle. However, the ratchet model requires appropriate cyclin dose–response thresholds. Here, we test the inhibition of mitotic exit in budding yeast using graded levels of stable mitotic cyclin (Clb2). In opposition to the ratchet model, stable levels of Clb2 introduced dose-dependent delays, rather than hard thresholds, that varied by mitotic exit event. The ensuing cell cycle was highly abnormal, suggesting a novel reason for cyclin degradation. Cdc14 phosphatase antagonizes Clb2–Cdk, and Cdc14 is released from inhibitory nucleolar sequestration independently of stable Clb2. Thus, Cdc14/Clb2 balance may be the appropriate variable for mitotic regulation. Although our results are inconsistent with the aforementioned ODE model, revision of the model to allow Cdc14/Clb2 balance to control mitotic exit corrects these discrepancies, providing theoretical support for our conclusions. [ABSTRACT FROM AUTHOR]

Aims/Introduction The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map™ ( CM™) vs usual care in a university-based hospital primary care clinic. Materials and Methods This was a randomized, pragmatic clinical trial. Patients with type 2 diabetes were randomly assigned to structured education or usual care groups. The primary outcome was the difference in the mean change of glycated hemoglobin (HbA1c) from baseline to 12 months. Secondary outcomes included the percentage achieving therapeutic HbA1c goal and self-behavioral changes. Results A total of 245 patients were randomly assigned to two groups ( CM™ group n = 121; usual care group, n = 116). The absolute reduction of HbA1c was significantly greater in the CM™ group at 3 and 6 months (Δ = −0.59% and Δ = −1.13%, P < 0.01), but the difference was no longer statistically significant at 9 and 12 months (Δ = −0.43% and Δ = −0.49%), based on an intention-to-treat analysis. A per-protocol analysis showed the significant change was maintained at 12 months (Δ = −0.67%). In the intervention group, greater percentages of patients achieved their American Association of Diabetes Educators Self-Care Behaviours™ framework ( AADE7) behavioral goals at 3 months, in particular being active, problem-solving, reducing risk and health coping. Conclusions In type 2 diabetic patients with suboptimally controlled glucose, there were greater improvements in glucose control and self-care behavioral goals in those who underwent the CM™ education program compared with outcomes achieved in patients receiving usual care. [ABSTRACT FROM AUTHOR]

Multispectral remote sensing images are a very important data source, but its acquisition process is often affected by haze weather and other factors, resulting in the decline of image quality, blurred details and poor visual effect, which seriously affect their application and interpretation. To reduce the impact of haze on multispectral remote sensing image and improve the image clarity and the use value, a new haze removal method based on rolling deep learning and Retinex theory (RDLRT) was proposed here. It uses the rolling deep learning theory to realize the preliminary removal of image haze, and then calculates the peak signal‐to‐noise ratio (PSNR) value of the processed image, which is used to judge whether the obtained image is a stage effect image (SEI). Then, on the one hand, the SEI image is processed for colour saturation and brightness; on the other hand, the Retinex theory is used to further filter the haze of the SEI image. Finally, the results of the two processing are fused, and it is used as the restored image after removing the haze. A series of validation experiments were carried out with true multispectral remote sensing images, outdoor colour images and different methods, and good experimental results were obtained. The purpose of removing image haze and improving image quality is achieved. Through the comparison of these experiments, it is concluded that the RDLRT algorithm proposed in this paper can not only effectively remove haze in images, but also maintain good details and colour of the image, which has some popularization values for image pre‐processing and restoration. [ABSTRACT FROM AUTHOR]

Summary: Osmotic stress influences root system architecture, and polar auxin transport (PAT) is well established to regulate root growth and development. However, how PAT responds to osmotic stress at the molecular level remains poorly understood. In this study, we explored whether and how the auxin efflux carrier PIN‐FORMED3 (PIN3) participates in osmotic stress‐induced root growth inhibition in Arabidopsis (Arabidopsis thaliana).We observed that osmotic stress induces a HD‐ZIP II transcription factor‐encoding gene HOMEODOMAIN ARABIDOPSIS THALIANA2 (HAT2) expression in roots. The hat2 loss‐of‐function mutant is less sensitive to osmotic stress in terms of root meristem growth. Consistent with this phenotype, whereas the auxin response is downregulated in wild‐type roots under osmotic stress, the inhibition of auxin response by osmotic stress was alleviated in hat2 roots. Conversely, transgenic lines overexpressing HAT2 (Pro35S::HAT2) had shorter roots and reduced auxin accumulation compared with wild‐type plants.PIN3 expression was significantly reduced in the Pro35S::HAT2 lines. We determined that osmotic stress‐mediated repression of PIN3 was alleviated in the hat2 mutant because HAT2 normally binds to the promoter of PIN3 and inhibits its expression.Taken together, our data revealed that osmotic stress inhibits root growth via HAT2, which regulates auxin activity by directly repressing PIN3 transcription. [ABSTRACT FROM AUTHOR]

Monodisperse ZrO2 ceramic beads with size larger than 1 mm have been prepared by an improved micro‐droplet spray forming process, through which a compressor and a dispenser were employed to produce droplets continuously. Furthermore, the slurry recipe and drying temperature have been optimized to enhance the sphericity and smoothness of the beads. The sintered ZrO2 ceramic beads present promising mechanical performance, including a relative density of 84.6%, a crush strength of 256.2 ± 36.6 N as well as a Vickers hardness of 1344.4 ± 58.3 HV. Such procedure reveals great potential in mass production of ceramic beads. [ABSTRACT FROM AUTHOR]

In chloroplasts, thiol/disulfide-redox-regulated proteins have been linked to numerous metabolic pathways. However, the biochemical system for disulfide bond formation in chloroplasts remains undetermined. In the present study, we characterized an oxidoreductase, AtVKOR-DsbA, encoded by the gene At4g35760 as a potential disulfide bond oxidant in Arabidopsis. The gene product contains two distinct domains: an integral membrane domain homologous to the catalytic subunit of mammalian vitamin K epoxide reductase (VKOR) and a soluble DsbA-like domain. Transient expression of green fluorescent protein fusion in Arabidopsis protoplasts indicated that AtVKOR-DsbA is located in the chloroplast. The first 45 amino acids from the N-terminus were found to act as a transit peptide targeting the protein to the chloroplast. An immunoblot assay of chloroplast fractions revealed that AtVKOR-DsbA was localized in the thylakoid. A motility complementation assay showed that the full-length of AtVKOR-DsbA, if lacking its transit peptide, could catalyze the formation of disulfide bonds. Among the 10 cysteine residues present in the mature protein, eight cysteines (four in the AtVKOR domain and four in the AtDsbA domain) were found to be essential for promoting disulfide bond formation. The topological arrangement of AtVKOR-DsbA was assayed using alkaline phosphatase sandwich fusions. From these results, we developed a possible topology model of AtVKOR-DsbA in chloroplasts. We propose that the integral membrane domain of AtVKOR-DsbA contains four transmembrane helices, and that both termini and the cysteines involved in catalyzing the formation of disulfide bonds face the oxidative thylakoid lumen. These studies may help to resolve some of the issues surrounding the structure and function of AtVKOR-DsbA in Arabidopsis chloroplasts. Structured digital abstract [ABSTRACT FROM AUTHOR]

Objective [ABSTRACT FROM AUTHOR]

Especially after injury, extra care on the periphery of damage will be activated by central sensitization mechanism, during which, touching the wound genially can induce pain. Inspired by the pain-perceptual system of human body, the multimode pain-perceptual system (MMPPS) can provide effective protection for electronic skin. Multi-Mode Pain-Perceptual System: Bio-Inspired Multi-Mode Pain-Perceptual System (MMPPS) with Noxious Stimuli Warning, Damage Localization, and Enhanced Damage Protection (Adv. Sci. 10/2021). [Extracted from the article]

Aims: SUMOylation is a posttranslational modification related to multiple human diseases. SUMOylation can be reversed by classes of proteases known as the sentrin/SUMO‐specific proteases (SENPs). In the present study, we investigate the potential role of SENP1 in pericytes in the brain ischemia. Methods: Pericyte‐specific deletion of senp1 mice (Cspg4‐Cre; senp1f/f) were used for brain function and neuronal damage evaluation following brain ischemia. The cerebral blood vessels of diameter, velocity, and flux were performed in living mice by two‐photon laser scanning microscopy (TPLSM). Biochemical analysis and immunohistochemistry methods were used to address the role and mechanism of pericyte‐specific SENP1 in the pathological process of brain ischemia. A coculture model of HBVPs and HBMECs mimicked the BBB in vitro and was used to evaluate BBB integrity after glucose deprivation. Results: Our results showed that senp1‐specific deletion in pericytes did not affect the motor function and cognitive function of mice. However, the pericyte‐specific deletion of senp1 aggravated the infarct size and motor deficit following focal brain ischemia. Consistently, the TPLSM data demonstrated that SENP1 deletion in pericytes accelerated thrombosis formation in brain microvessels. We also found that pericyte‐specific deletion of senp1 exaggerated the neuronal damage significantly following brain ischemia in mice. Moreover, SENP1 knockdown in pericytes could activate the apoptosis signaling and disrupt the barrier integrity in vitro coculture model. Conclusions: Our findings revealed that targeting SENP1 in pericytes may represent a novel therapeutic strategy for neurovascular protection in stroke. [ABSTRACT FROM AUTHOR]

Summary: Lateral roots (LRs), which form in the plant postembryonically, determine the architecture of the root system. While negative regulatory factors that inhibit LR formation and are counteracted by auxin exist in the pericycle, these factors have not been characterised.Here, we report that SHI‐RELATED SEQUENCE5 (SRS5) is an intrinsic negative regulator of LR formation and that auxin signalling abolishes this inhibitory effect of SRS5. Whereas LR primordia (LRPs) and LRs were fewer and less dense in SRS5ox and Pro35S:SRS5‐GFP plants than in the wild‐type, they were more abundant and denser in the srs5‐2 loss‐of‐function mutant. SRS5 inhibited LR formation by directly downregulating the expression of LATERAL ORGAN BOUNDARIES‐DOMAIN 16 (LBD16) and LBD29.Auxin repressed SRS5 expression. Auxin‐mediated repression of SRS5 expression was not observed in the arf7‐1 arf19‐1 double mutant, likely because ARF7 and ARF19 bind to the promoter of SRS5 and inhibit its expression in response to auxin.Taken together, our data reveal that SRS5 negatively regulates LR formation by repressing the expression of LBD16 and LBD29 and that auxin releases this inhibitory effect through ARF7 and ARF19. [ABSTRACT FROM AUTHOR]

Reproductive factors associated with breast cancer risk may also affect the prognosis. This study aimed to evaluate the associations of multiple reproductive factors with breast cancer prognosis and the modifying effects of menopausal status. We obtained data from 3805 breast cancer patients recruited between October 2008 and June 2016 in Guangzhou. The subjects were followed up until 30 June 2018. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using multivariate Cox models to estimate the associations. It was found that there were U‐shaped patterns for the associations of age at first birth and durations from first/last birth to diagnosis with breast cancer prognosis. The adverse effects of old age at first birth [>30 years vs 23‐30 years, HR (95% CI): 1.59 (1.01‐2.50)] and long intervals from first [≥20 years vs 10‐19 years, HR (95% CI): 1.55 (1.07‐2.27)] or last [≥20 years vs 10‐19 years, HR (95% CI): 1.63 (1.08‐2.46)] birth to diagnosis on progression‐free survival (PFS) were significantly more pronounced among premenopausal women. Additionally, long interval (>5 years) between first and second birth was associated with a better PFS [HR (95% CI): 0.64 (0.42‐0.97)]. These results suggested that age at first birth, durations from first/last birth to diagnosis, and intervals between first and second birth should be taken into account when following the patients and assessing the prognosis of breast cancer, particularly for premenopausal patients. These findings would also have implications for further insight into the mechanisms of breast cancer development. [ABSTRACT FROM AUTHOR]

Primary familial brain calcification (PFBC) is a rare neurological disorder. Mutations in five genes (SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG) have been linked to PFBC. Here, we used SYBR green‐based real‐time quantitative polymerase chain reaction (PCR) assay and denaturing high‐performance liquid chromatography analysis to detect copy number variants (CNVs) in 20 unrelated patients with PFBC, negatively sequenced for the five known genes. We identified three deletions in SLC20A2, including a large de novo full gene deletion and two exonic deletions confined to exon 2 and exon 6, respectively. Subsequent linked‐read whole‐genome sequencing of the patient with the large deletion showed a 1.7 Mb heterozygous deletion which removed the entire coding regions of SLC20A2 as well as 21 other genes. In the family with a deletion of exon 6, a missense variant of uncertain significance (SLC20A2: p.E267Q) also co‐segregated with the disease. Functional assay showed the deletion could result in significantly impaired phosphate transport, whereas the p.E267Q variant did not. Our results confirm that deletion in SLC20A2 is a causal mechanism for PFBC and highlight the importance of functional study for classifying a rare missense variant as (likely) pathogenic. [ABSTRACT FROM AUTHOR]

Summary: Aims: Autism spectrum disorder (ASD) is a wide range of neurodevelopmental disorders involving deficits in social interaction and communication. Unfortunately, autism remains a scientific and clinical challenge owing to the lack of understanding the cellular and molecular mechanisms underlying it. This study aimed to investigate the pathophysiological mechanism underlying leukocyte‐endothelial adhesion in autism‐related neurovascular inflammation. Methods: Male BTBR T+tf/J mice were used as an autism model. The dynamic pattern of leukocyte‐endothelial adhesion in mouse cerebral vessels was detected by two‐photon laser scanning microscopy (TPLSM). Using FACS, RT‐PCR, and Western blotting, we explored the expression of cell adhesion molecules, the mRNA expression of endothelial chemokine, the protein levels of cathepsin B, and inflammatory mediators. Results: We found a significant increase in leukocyte‐endothelial adhesion in BTBR mice, accompanied by elevated expression of the adhesion molecule neutrophils CD11b and endothelial ICAM‐1. Our data further indicate that elevated neutrophil cathepsin B levels contribute to elevated endothelial chemokine CXCL7 levels in BTBR mice. The pharmacological inhibition of cathepsin B reverses the enhanced leukocyte‐endothelial adhesion in the cerebral vessels of autistic mice. Conclusion: Our results revealed the prominent role of cathepsin B in modulating leukocyte‐endothelial adhesion during autism‐related neurovascular inflammation and identified a promising novel approach for autism treatment. [ABSTRACT FROM AUTHOR]

Abstract: The human CGB5 gene encodes chorionic gonadotropin (hCG)β 5, which is aberrantly expressed in trophoblastic neoplasm and in some non‐trophoblastic neoplasms. Fucntional studies observed that it involved tumor initiation, growth, and metastatic outgrowth. In this study, using data from the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA)‐stomach adenocarcinoma (STAD), we assessed the independent prognostic value of CGB5 expression in patients with primary gastric cancer (GC). Results showed that CGB5 expression was nearly not expressed in normal GC tissues. In comparison, its expression was detected in 214 of the 415 primary GC cases (51.6%) in TCGA‐STAD and was associated with poor response to primary therapy and a higher risk of recurrence and death. In early stages, CGB5 expression was not a prognostic factor in terms of OS (HR: 1.448; 95% CI: 0.811–2.588, P = 0.211) or RFS (HR: 1.659; 95% CI: 0.778–3.540, P = 0.190). However, its expression was independently associated with unfavorable OS (HR: 1.719; 95% CI: 1.115–2.651, P = 0.014) and RFS (HR: 3.602; 95% CI: 1.708–7.598, P = 0.001) in advanced stages. Using deep sequencing data from TCGA‐STAD, we found that CGB5 expression was not related to its genetic amplification or DNA methylation in GC. Based on these findings, we infer that CGB5 expression is common in GC patients and its expression might independently predict poor OS and RFS in advanced stages, but not in early stages of GC. [ABSTRACT FROM AUTHOR]

Summary: Although nitric oxide (NO) is known to regulate root growth, the factor(s) modulating NO during this process have not yet been elucidated. Here, we identified Arabidopsis WD40‐REPEAT 5a (WDR5a) as a novel factor that functions in root growth by modulating NO accumulation. The wdr5a‐1 mutant accumulated less NO and produced longer roots than the wild type, whereas the WDR5a overexpression lines had the opposite phenotype. The role of NO was further supported by our observation that the NO donor sodium nitroprusside (SNP) and the NO scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (cPTIO) rescued the root meristem growth phenotypes of the wdr5a‐1 and WDR5a overexpression lines, respectively. The regulation of root growth by WDR5a was found to involve auxin because the auxin levels were similar in SNP‐treated wdr5a‐1 and wild‐type roots, but higher in untreated wdr5a‐1 roots than in wild‐type roots. In addition, the wdr5a‐1 mutant had higher production and activity levels of the auxin biosynthetic enzyme TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS1 (TAA1), in contrast to its reduced expression and activity in the WDR5a overexpression lines, and the increased root meristem growth in wdr5a‐1 was suppressed by treatment with l‐kynurenine, which inhibits TAA1, as well as by mutating TAA1. WDR5a therefore functions in root meristem growth by maintaining NO homeostasis, and thus TAA1‐mediated auxin biosynthesis. [ABSTRACT FROM AUTHOR]

Aims The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Results Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in Ca MKII phosphorylation in Cdh5Cre;ErbB4 f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4 f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho- ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Conclusions Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders. [ABSTRACT FROM AUTHOR]

Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm ( RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm. The catalytic process of Tmm consists of a reductive half-reaction and an oxidative half-reaction. In the reductive half-reaction, FAD is reduced and a C4a-hydroperoxyflavin intermediate forms. In the oxidative half-reaction, this intermediate attracts TMA through electronic interactions. After TMA binding, NADP+ bends and interacts with D317, shutting off the entrance to create a protected micro-environment for catalysis and exposing C4a-hydroperoxyflavin to TMA for oxidation. Sequence analysis suggests that the proposed catalytic mechanism is common for bacterial Tmms. These findings reveal the catalytic process of TMA oxidation by marine bacterial Tmm and first show that NADP+ undergoes a conformational change in the oxidative half-reaction of FMOs. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the use of maternal health care services by internal migrants in view of their migration status.Methods: Cross-sectional household survey in two cities of Jiangsu Province. Questions elicited data on socioeconomic information and MHC service use (pre-natal examination, post-natal visit, pre-natal health education). Chi-square tests and multivariate logistic regression analyses were used to identify factors associated with MHC service use.Results: A total of 946 married women were recruited, of whom 22.3% were internal migrants. Compared to local residents, migrants were five times less likely to attend pre-natal examinations (84.4% vs. 91.7%; OR = 0.49, P = 0.002), three times less likely to have post-natal visits (15.6% vs. 50.2%; OR = 0.18, P < 0.001) and less likely to attend health education during pregnancy (87.0% vs. 95.7%; OR = 0.30, P < 0.001). Multivariate logistic regression also revealed a lower proportion of MHC use among migrants (ORm 0.52, 0.16, and 0.3, respectively).Conclusions: Internal migrants in Jiangsu Province underuse MHC services to a significant degree. More attention needs to be paid to pregnant migrant women, as they are vulnerable group in society. [ABSTRACT FROM AUTHOR]