Topological chiral crystals with helicoid-arc quantum states.

The quantum behaviour of electrons in materials is the foundation of modern electronics and information technology1-11, and quantum materials with topological electronic and optical properties are essential for realizing quantized electronic responses that can be used for next generation technology. Here we report the first observation of topological quantum properties of chiral crystals6,7 in the RhSi family. We find that this material class hosts a quantum phase of matter that exhibits nearly ideal topological surface properties originating from the crystals' structural chirality. Electrons on the surface of these crystals show a highly unusual helicoid fermionic structure that spirals around two high-symmetry momenta, indicating electronic topological chirality. The existence of bulk multiply degenerate band fermions is guaranteed by the crystal symmetries; however, to determine the topological invariant or charge in these chiral crystals, it is essential to identify and study the helicoid topology of the arc states. The helicoid arcs that we observe on the surface characterize the topological charges of ±2, which arise from bulk higher-spin chiral fermions. These topological conductors exhibit giant Fermi arcs of maximum length (π), which are orders of magnitude larger than those found in known chiral Weyl fermion semimetals5,8-11. Our results demonstrate an electronic topological state of matter on structurally chiral crystals featuring helicoid-arc quantum states. Such exotic multifold chiral fermion semimetal states could be used to detect a quantized photogalvanic optical response, the chiral magnetic effect and other optoelectronic phenomena predicted for this class of materials6.

Phenotypic features, prevalence of KCNJ11-MODY in Chinese patients with early-onset diabetes and a literature review.

OBJECTIVE: Gain-of-function (GOF) variants of KCNJ11 cause neonate diabetes and maturity-onset diabetes of the young (KCNJ11-MODY), while loss-of-function (LOF) variants lead to hyperinsulinemia hypoglycemia and subsequent diabetes. Given the limited research of KCNJ11-MODY, we aimed to analyse its phenotypic features and prevalence in Chinese patients with early-onset type 2 diabetes (EOD). DESIGN, PATIENTS AND MEASUREMENTS: We performed next-generation sequencing on 679 Chinese EOD patients to screen for KCNJ11 exons variants. Bioinformatics prediction and the American College of Medical Genetics and Genomics guidelines was used to determine the pathogenicity and diagnosed KCNJ11-MODY. A literature review was conducted to investigate the phenotypic features of KCNJ11-MODY. RESULTS: We identified six predicted deleterious rare variants in six EOD patients (0.88%). They were classified as uncertain significance (variant of uncertain significance [VUS]), but more common in this EOD cohort than a general Chinese population database, however, without significant difference (53/10,588, 0.50%) (p = .268). Among 80 previously reported patients with KCNJ11-MODY, 23.8% (19/80) carried 9 (32.1%) LOF variants, who had significantly older age at diagnosis, higher birthweight and higher fasting C-peptide compared to patients with GOF variants. Many patients carrying VUS were not correctly diagnosed. CONCLUSIONS: Some rare variants of KCNJ11 might contribute to the development of Chinese EOD, although available evidence has not enough power to support them as cause of KCNJ11-MODY. The clinical features of LOF variants were different from GOF variants in KCNJ11-MODY patients. It is necessary to evaluate the pathogenicity of VUS through function experiments.

A nomogram for predicting food allergy in infants with feeding problems and malnutrition.

BACKGROUND AND OBJECTIVE: As oral food challenge (OFC) cannot be performed routinely in the general outpatient, this study aimed to construct a nomogram to predict the odds of food allergy in infants with idiopathic feeding problems and malnutrition. METHODS: From August 2018 to December 2021, 289 infants (median age, 6 months; P25-P75, 4-8) with idiopathic feeding problems and malnutrition were enrolled from seven hospitals in Shanghai, China. Food allergy was defined as a positive response to a skin prick test or OFC, with gastrointestinal, dermatologic, or respiratory symptom improvement after 4 weeks of avoidance of the suspected food. Demographic characteristics, Cow's Milk-related Symptom Scores (CoMiSS), and blood eosinophil amounts were evaluated for their associations with food allergy. Multivariable logistic regression analysis was used to identify variables to develop a nomogram model with the bootstrapped-concordance index as an assessment metric. RESULTS: Totally 249 of 289 infants had food allergy (86.2%). After logistic regression analysis, the feeding pattern (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 2.13-13.09), a family history of allergy (OR = 1.79, 95% CI: 0.71-4.51), CoMiSS (OR = 1.45, 95% CI: 1.19-1.77), and eosinophil percentage (OR = 1.33, 95% CI: 1.11-1.60) were used to develop the model, which had a good performance with an area under the curve of 0.868 (95% CI: 0.792-0.944) and a bootstrapped-concordance index of 0.868. CONCLUSION: Food allergy is common in infants with idiopathic feeding problems and malnutrition. The developed nomogram may help identify infants with food allergy for further diagnosis.

Beyond Single-Cycle Autonomous Molecular Machines: Light-Powered Shuttling in a Multi-Cycle Reaction Network.

Biomolecular machines autonomously convert energy into functions, driving systems away from thermodynamic equilibrium. This energy conversion is achieved by leveraging complex, kinetically asymmetric chemical reaction networks that are challenging to characterize precisely. In contrast, all known synthetic molecular systems in which kinetic asymmetry has been quantified are well described by simple single-cycle networks. Here, we report on a unique light-driven [2]rotaxane that enables the autonomous operation of a synthetic molecular machine with a multi-cycle chemical reaction network. Unlike all prior systems, the present one exploits a photoactive macrocycle, which features a different photoreactivity depending on the binding sites at which it resides. Furthermore, E to Z isomerization reverses the relative affinity of the macrocycle for two binding sites on the axle, resulting in a multi-cycle network. Building on the most recent theoretical advancements, this work quantifies kinetic asymmetry in a multi-cycle network for the first time. Our findings represent the simplest rotaxane capable of autonomous shuttling developed so far and offer a general strategy to generate and quantify kinetic asymmetry beyond single-cycle systems.

Lead acetate induces cartilage defects and bone loss in zebrafish embryos by disrupting the GH/IGF-1 axis.

Skeletal system toxicity due to lead exposure has attracted extensive attention in recent years, but few studies focus on the skeletal toxicity of lead in the early life stages of zebrafish. The endocrine system, especially the GH/IGF-1 axis, plays an important role in bone development and bone health of zebrafish in the early life. In the present study, we investigated whether lead acetate (PbAc) affected the GH/IGF-1 axis, thereby causing skeletal toxicity in zebrafish embryos. Zebrafish embryos were exposed to lead PbAc between 2 and 120 h post fertilization (hpf). At 120 hpf, we measured developmental indices, such as survival, deformity, heart rate, and body length, and assessed skeletal development by Alcian Blue and Alizarin Red staining and the expression levels of bone-related genes. The levels of GH and IGF-1 and the expression levels of GH/IGF-1 axis-related genes were also detected. Our data showed that the LC50 of PbAc for 120 h was 41 mg/L. Compared with the control group (0 mg/L PbAc), after PbAc exposure, the deformity rate increased, the heart rate decreased, and the body length was shortened at various time periods, in the 20-mg/L group at 120 hpf, the deformity rate increased by 50 fold, the heart rate decreased by 34%, and the body length shortened by 17%. PbAc altered cartilage structures and exacerbated bone loss in zebrafish embryos; in addition, PbAc exposure down-regulated the expression of chondrocyte (sox9a, sox9b), osteoblast (bmp2, runx2) and bone mineralization-related genes (sparc, bglap), and up-regulated the expression of osteoclast marker genes (rankl, mcsf). The GH level increased and the IGF-1 level declined significantly. The GH/IGF-1 axis related genes (ghra, ghrb, igf1ra, igf1rb, igf2r, igfbp2a, igfbp3, igfbp5b) were all decreased. These results suggested that PbAc inhibited the differentiation and maturation of osteoblasts and cartilage matrix, promoted the formation of osteoclasts, and ultimately induced cartilage defects and bone loss by disrupting the GH/IGF-1 axis.

Unconventional Hysteretic Transition in a Charge Density Wave.

Hysteresis underlies a large number of phase transitions in solids, giving rise to exotic metastable states that are otherwise inaccessible. Here, we report an unconventional hysteretic transition in a quasi-2D material, EuTe_{4}. By combining transport, photoemission, diffraction, and x-ray absorption measurements, we observe that the hysteresis loop has a temperature width of more than 400 K, setting a record among crystalline solids. The transition has an origin distinct from known mechanisms, lying entirely within the incommensurate charge density wave (CDW) phase of EuTe_{4} with no change in the CDW modulation periodicity. We interpret the hysteresis as an unusual switching of the relative CDW phases in different layers, a phenomenon unique to quasi-2D compounds that is not present in either purely 2D or strongly coupled 3D systems. Our findings challenge the established theories on metastable states in density wave systems, pushing the boundary of understanding hysteretic transitions in a broken-symmetry state.

Role of Equilibrium Fluctuations in Light-Induced Order.

Engineering novel states of matter with light is at the forefront of materials research. An intensely studied direction is to realize broken-symmetry phases that are "hidden" under equilibrium conditions but can be unleashed by an ultrashort laser pulse. Despite a plethora of experimental discoveries, the nature of these orders and how they transiently appear remain unclear. To this end, we investigate a nonequilibrium charge density wave (CDW) in rare-earth tritellurides, which is suppressed in equilibrium but emerges after photoexcitation. Using a pump-pump-probe protocol implemented in ultrafast electron diffraction, we demonstrate that the light-induced CDW consists solely of order parameter fluctuations, which bear striking similarities to critical fluctuations in equilibrium despite differences in the length scale. By calculating the dynamics of CDW fluctuations in a nonperturbative model, we further show that the strength of the light-induced order is governed by the amplitude of equilibrium fluctuations. These findings highlight photoinduced fluctuations as an important ingredient for the emergence of transient orders out of equilibrium. Our results further suggest that materials with strong fluctuations in equilibrium are promising platforms to host hidden orders after laser excitation.

Associations between maternal vitamin D status during three trimesters and cord blood 25(OH)D concentrations in newborns: a prospective Shanghai birth cohort study.

PURPOSE: Prenatal vitamin D (VitD) deficiency influences children's health in later life. We aimed to test the associations between maternal VitD status in each of the three trimesters of pregnancy and cord blood 25(OH)D concentrations in newborns. METHODS: Participants were pregnant women recruited from the Shanghai Birth Cohort (SBC) (n = 1100). Of all the participants, 946 completed the collection of venous blood at early (< 16 weeks, T1), mid- (24-28 weeks, T2), and late (32-34 weeks, T3) pregnancy as well as the corresponding cord blood in the newborns. Maternal serum 25(OH)D concentrations were measured by LC-MS/MS, and the information on confounding factors was obtained through a standardized questionnaire. RESULTS: The mean 25(OH)D concentrations at time points T1, T2, T3 in maternal blood and cord blood of the newborns were 26.31 ng/mL, 31.92 ng/mL, 35.62 ng/mL, and 19.77 ng/mL, respectively. Neonatal 25(OH)D level in cord blood was positively correlated with maternal serum 25(OH)D levels at each trimester, and the strongest correlation was found at time point T3. CONCLUSION: Maternal 25(OH)D concentrations at each trimester were positively associated with neonatal VitD status in cord blood, and the strongest correlation was found in the late stage of pregnancy, which could be considered as a sensitive time window. Attention should be paid to the nutritional status of VitD during pregnancy to better prevent the VitD deficiency in neonates.

The effects of exercise on insulin, glucose, IGF-axis and CRP in cancer survivors: Meta-analysis and meta-regression of randomised controlled trials.

BACKGROUND: The purpose of this study was to investigate the relationship between physical activity and biological mediators of cancer recurrence and survival. METHODS: We conducted a comprehensive literature search of PubMed, ScienceDirect and Web of Science for randomised controlled trials examining the association between physical activity and C-reactive protein (CRP), glucose, insulin, insulin resistance and insulin growth factor-one (IGF-1) up to December 2017. Standardised mean difference (SMD) scores were calculated, and meta-regression was performed. RESULTS: The meta-analysis indicated that survivors randomised to physical activity conditions experienced greater improvements in Insulin (SMD = -0.59; 95% CI, -1.05 to -0.14), CRP (SMD = -0.52; 95% CI, -0.87 to -0.17), insulin resistance (SMD = -0.20; 95% CI, -0.41 to -0.003) and glucose (SMD = -0.19; 95% CI, -0.35 to -0.02) than survivors randomised to control conditions. The meta-regression showed that study duration was positively, albeit marginally related (p = .056) to change in CRP levels among survivors in the physical activity conditions. Furthermore, higher baseline insulin levels in the physical activity conditions were associated with improving insulin levels throughout the intervention (p = .007). CONCLUSIONS: Promoting physical activity throughout the survivorship continuum is an effective intervention strategy for improving levels of insulin, glucose control, insulin resistance and CRP among cancer survivors.

Development of a sensitive HPLC-MS/MS method for 25-hydroxyvitamin D2 and D3 measurement in capillary blood.

BACKGROUND: Measurement of 25-hydroxyvitamin D [25(OH)D)] levels is important. The current method requires a relatively large volume of serum. To minimize the amount of serum needed, we established a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to measure 25(OH)D in capillary serum. METHODS: Venous blood and fingertip blood were collected from 90 participants. Volumes of 100 µL of venous serum and 20 µL of capillary serum were collected. The serum samples were pretreated by protein removal, extraction and concentration, and an HPLC-MS/MS method based on chromatographic separation and multi reactive ion monitoring was conducted. The intra- and inter-batch variation coefficients were less than 10% for both 25-hydroxyvitamin D3 [25(OH)D3 ] and 25-hydroxyvitamin D2 [25(OH)D2 )]. For venous specimens, the accuracies were 3.87% and 4.91%, respectively. For capillary specimens, the accuracies were 1.65% and 5.32%, respectively. RESULTS: The limit of detection (LOD) of 25(OH)D3 was 0.01 ng/mL, and the LOD of 25(OH)D2 was 0.05 ng/mL. The results showed that the mean concentration of 25(OH)D in venous blood was 22.56 ± 9.50 ng/mL, while the mean concentration of 25(OH)D in capillary blood was 18.14 ± 7.86 ng/mL. Furthermore, the adjusted capillary blood 25(OH)D level was 22.99 ± 10.24 ng/mL by the correction formula in our study. Similarly, the mean concentration of 25(OH)D3 in capillary blood was 17.98 ± 7.98 ng/mL. The adjusted capillary blood 25(OH)D3 level was 22.85 ± 10.42 ng/mL. No difference in the content of 25(OH)D or 25(OH)D3 was found between venous serum and corrected capillary serum. The correlation coefficients between venous and corrected capillary concentrations of 25(OH)D and 25(OH)D3 were 0.7941 and 0.8103, respectively, and the areas under the receiver operating characteristic curve were 0.9367 and 0.9565, respectively. CONCLUSIONS: This capillary blood method requires minimal sample preparation and is suitable for routine use in the 25(OH)D detection.

Dynamical Slowing-Down in an Ultrafast Photoinduced Phase Transition.

Complex systems, which consist of a large number of interacting constituents, often exhibit universal behavior near a phase transition. A slowdown of certain dynamical observables is one such recurring feature found in a vast array of contexts. This phenomenon, known as critical slowing-down, is well studied mostly in thermodynamic phase transitions. However, it is less understood in highly nonequilibrium settings, where the time it takes to traverse the phase boundary becomes comparable to the timescale of dynamical fluctuations. Using transient optical spectroscopy and femtosecond electron diffraction, we studied a photoinduced transition of a model charge-density-wave (CDW) compound LaTe_{3}. We observed that it takes the longest time to suppress the order parameter at the threshold photoexcitation density, where the CDW transiently vanishes. This finding can be captured by generalizing the time-dependent Landau theory to a system far from equilibrium. The experimental observation and theoretical understanding of dynamical slowing-down may offer insight into other general principles behind nonequilibrium phase transitions in many-body systems.

Three-Dimensional Hierarchical Porous Carbon Cathode Derived from Waste Tea Leaves for the Electrocatalytic Degradation of Phenol.

Tea leaves have been explored as an economically viable and environmentally friendly source of biomass carbon. Tea leaf porous carbon (TPC) with a three-dimensional (3D) structure was prepared by a potassium hydroxide pretreatment and high-temperature calcination method, and the preparation process was simple and self-templating. The prepared TPC has a large specific surface area (1620.05 m2 g-1), three-dimensional multilayer pore structure, uniform pore size, and high oxygen content (15.51%). Both the calcination temperature and the activation level have an effect on the structure and performance of the TPC. The TPC electrode can generate a large amount of hydrogen peroxide in the initial stage of the degradation process, thereby increasing the amount of hydroxyl radicals generated and removing organic pollutants. Therefore, phenol was used to test the degradation effects and evaluate the degradation performance of TPC. Under suitable degradation conditions, TPC-800-2 showed a 95.41% degradation rate after 120 min of degradation, which is superior to that of other calcination temperatures and activation levels. The removal efficiency of chemical oxygen demand after 180 min was 90.0% and showed good stability after being used 20 times. Our work illustrates that a simple, high-performance self-templating synthetic strategy for producing novel 3D-TPC from biomass sources can play a significant role in the actual wastewater treatment of other biomass materials.

Reliability Assessment of Deflection Limit State of a Simply Supported Bridge using vibration data and Dynamic Bayesian Network Inference.

Structural health monitoring (SHM) has been widely used in all kinds of bridges. It is significant to accurately assess the serviceability and reliability of bridge subjected to severe conditions by SHM technique. Bridge deflection as an essential evaluation index can reflect structural condition perfectly. In this study, an approach for deflection calculation and reliability assessment of simply supported bridge is presented. Firstly, a bridge deflection calculation method is proposed based on modal flexibility and Kriging method improved by artificial bee colony algorithm. Secondly, a dynamic Bayesian network is employed to evaluate the deflection reliability combined with monitoring results which include modal frequency, mode shape, environmental temperature, and humidity. A linear regression model is established to analyze the relationship between modal parameters and environmental factors. Thirdly, a simply supported bridge is constructed and monitored to verify the effectiveness of the proposed method. The results reveal that the proposed method can precisely calculate the bridge deflection. Finally, the time-dependent reliabilities of two cases are computed and the effects of monitoring factors on bridge deflection reliability are analyzed by sensitivity parameter. It indicates that the reliability is negatively correlated with temperature and more sensitive to mode shape than other three factors.

Topical application of quercetin improves wound healing in pressure ulcer lesions.

The ischaemia-reperfusion (I/R)-induced skin lesion has been identified as primary cause of pressure ulcers. To date, attempts to prevent pressure ulcers have not produced a significant improvement. Quercetin, one of the most widely distributed flavonoids in fruits and vegetables, exhibits its antioxidant and anti-inflammatory properties against many diseases, including ischaemic heart disease, atherosclerosis and renal injury. In vitro wound scratch assay was first used to assess the function of quercetin in wounding cell model. Next, animal pressure ulcers model was established with two cycles of I/R. The impact of quercetin in the wound recovery, immune cell infiltration and pro-inflammatory cytokines production was investigated in this model. Mechanistic regulation of quercetin at the wound site was also studied. Quercetin accelerated wound closure in cell scratch assay. Dose-response study suggested 1 µmol/L quercetin for in vivo study. In I/R injury model, quercetin treatment significantly accelerated wound closure, reduced immune cell infiltration and pro-inflammatory cytokines production. Signalling study showed quercetin treatment inhibited MAPK but not NFĸB activation. Quercetin treatment improved the wound healing process in I/R lesions by suppressing MAPK pathway. Our results supported that quercetin could be a potential therapeutic agent for pressure ulcers.

MiRNA-181b suppresses IGF-1R and functions as a tumor suppressor gene in gliomas.

MicroRNAs (miRNAs) are single-stranded, 18- to 23-nt RNA molecules that function as regulators of gene expression. Previous studies have shown that microRNAs play important roles in human cancers, including gliomas. Here, we found that expression levels of miR-181b were decreased in gliomas, and we identified IGF-1R as a novel direct target of miR-181b. MiR-181b overexpression inhibited cell proliferation, migration, invasion, and tumorigenesis by targeting IGF-1R and its downstream signaling pathways, PI3K/AKT and MAPK/ERK1/2. Overexpression of IGF-1R rescued the inhibitory effects of miR-181b. In clinical specimens, IGF-1R was overexpressed, and its protein levels were inversely correlated with miR-181b expression. Taken together, our results indicate that miR-181b functions in gliomas to suppress growth by targeting the IGF-1R oncogene and that miR-181b may serve as a novel therapeutic target for gliomas.

A new electrolyte for molten carbonate decarbonization.

The molten Li2CO3 transformation of CO2 to oxygen and graphene nanocarbons (GNCs), such as carbon nanotubes, is a large scale process of CO2 removal to mitigate climate change. Sustainability benefits include the stability and storage of the products, and the GNC product value is an incentive for carbon removal. However, high Li2CO3 cost and its competitive use as the primary raw material for EV batteries are obstacles. Common alternative alkali or alkali earth carbonates are ineffective substitutes due to impure GNC products or high energy limitations. A new decarbonization chemistry utilizing a majority of SrCO3 is investigated. SrCO3 is much more abundant, and an order of magnitude less expensive, than Li2CO3. The equivalent affinities of SrCO3 and Li2CO3 for absorbing and releasing CO2 are demonstrated to be comparable, and are unlike all the other alkali and alkali earth carbonates. The temperature domain in which the CO2 transformation to GNCs can be effective is <800 °C. Although the solidus temperature of SrCO3 is 1494 °C, it is remarkably soluble in Li2CO3 at temperatures less than 800 °C, and the electrolysis energy is low. High purity CNTs are synthesized from CO2 respectively in SrCO3 based electrolytes containing 30% or less Li2CO3.

Associations between Longitudinal Maternal and Cord Blood Vitamin D Status and Child Growth Trajectories Up to 4 Years of Age.

The current study aimed to explore the combined and individual effects of vitamin D (VitD) status in three trimesters during pregnancy and cord blood (CB) on child growth trajectories from birth to 4 years of age. Pregnant women (n = 1100) were recruited between 2013 and 2016 in the Shanghai Birth Cohort (SBC) Study. A total of 959 mother-child dyads were included. VitD status was measured by LC-MS/MS at three trimesters (T1, T2, T3) and CB. Children's weight, length/height, and head circumference were assessed at birth, 42 days, 6, 12, 24 months, and 4 years of age, and standardized into z-scores [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HCZ) and weight-for-length z-score (WLZ)]. Using the group-based trajectory model (GBTM), the trajectories of the four growth parameters were categorized into discrete groups. The generalized estimating equation (GEE) was employed to analyze the mixed effect of 25(OH)D throughout pregnancy on growth trajectories. The association between 25(OH)D status and each growth trajectory group was examined by multivariable logistic regression. Each 10 ng/mL increase in 25(OH) throughout three trimesters was not associated with four anthropometric parameters. Each 10 ng/mL increase in VitD in T3 was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.75; 95% CI: 0.62, 0.91; p < 0.01). Each 10 ng/mL increase in VitD in CB was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.57; 95% CI: 0.43, 0.76; p < 0.01). No significant association was found between maternal or CB VitD and LAZ or HCZ. Three trimesters' VitD throughout pregnancy had no persistent effect on the offspring's growth trajectory. However, higher VitD status in the third trimester and CB related to a lower risk of high-increasing WAZ from birth to 4 years of age. Elevated VitD levels in late pregnancy and cord blood may protect against continuous early-life weight growth at high levels.

Ultrafast high-endurance memory based on sliding ferroelectrics.

The persistence of voltage-switchable collective electronic phenomena down to the atomic scale has extensive implications for area- and energy-efficient electronics, especially in emerging nonvolatile memory technology. We investigate the performance of a ferroelectric field-effect transistor (FeFET) based on sliding ferroelectricity in bilayer boron nitride at room temperature. Sliding ferroelectricity represents a different form of atomically thin two-dimensional (2D) ferroelectrics, characterized by the switching of out-of-plane polarization through interlayer sliding motion. We examined the FeFET device employing monolayer graphene as the channel layer, which demonstrated ultrafast switching speeds on the nanosecond scale and high endurance exceeding 1011 switching cycles, comparable to state-of-the-art FeFET devices. These characteristics highlight the potential of 2D sliding ferroelectrics for inspiring next-generation nonvolatile memory technology.

Involvement of basolateral amygdala-rostral anterior cingulate cortex in mechanical allodynia and anxiety-like behaviors and potential mechanisms of electroacupuncture.

AIMS: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. METHODS: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. RESULTS: EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. CONCLUSION: BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.

Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes.

OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.