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IntroductionNonketotic hyperglycinemia (NKH) is a rare, life-threatening genetic disorder. The patients usually show heterogeneous and nonspecific symptoms, resulting in diagnosis challenges using conventional approaches. Here, the clinical presentation and genetic features of 20 Chinese patients were examined and reported in order to clarify the natural history and prognosis of NKH in China.MethodsThe Human Gene Mutation Database and literature regarding NKH in China were reviewed. Age of onset, clinical characteristics, genetic analysis, cranial magnetic resonance imaging (MRI) and electroencephalography (EEG) examinations, and outcome of the patients were analyzed. Natural history experiences and follow-up assays for five patients who were followed in our center were described.ResultsAmong all 20 NKH patients, 17 (85%) had the neonatal type and 3 (15%) had the infantile type, no late-onset cases were detected. Patients showed up for admission with a history of seizures (15/20), lethargy (14/20), hypotonia (11/20), apnea (9/20), and feeble sobbing (4/20). Brain MRI findings included abnormal signals in the internal capsule, cerebellum, or brainstem (6/14), dysplasia of the corpus callosum (5/14), and white matter abnormalities (3/14). EEG evaluations showed anomalies such as burst suppression (4/8) and hypsarrhythmia and/or epileptic activity (6/8). Median values of cerebrospinal fluid (CSF) glycine levels, plasma glycine levels and CSF/plasma glycine ratios were135.2 (range, 6.3–546.3) μmol/L, 998.2 (range,75–3,084) μmol/L, 0.16 (range, 0.03–0.60) respectively. Genetic analyses revealed four new variations and GLDC, AMT gene abnormalities in 13 (65%), 7 (35%) case, respectively. Prognosis information was available for 18 cases: nine patients died, eight in the neonatal period. Among the nine survivors, varying developmental disorders were observed.DiscussionDifferent disease processes and outcomes were found in Chinese NKH patients, according to this study. The initial clinical presentations, CSF glycine levels and CSF to plasma glycine ratios do not reliably predict prognosis, while MRI and EEG abnormalities may indicate a poor outlook. NKH diagnosis should be considered for neonates presenting specific symptoms. The present survey provides clinical data that support the development of a standardized protocol for diagnosing and treating NKH in China.

Abstract Recently, a possible room-temperature superconductor known as LK-99 (Pb10-xCux(PO4)6O (0.9

Avalanches are sudden, destructive, and extremely difficult to forecast natural disasters that can result in numerous fatalities and extensive property damage. Given the immense danger posed by avalanches, there is a significant amount of attention paid to accurately predicting these events. We investigate the predictability of large avalanches in a class of self-organizing systems, which change their internal structure or function in response to external circumstances by manipulating or organizing other elements of the same system. Here, we propose a practical relaxation time to replace a traditional recovery time, and importantly, the relaxation time does not require the removal of part of the resources (perturb state variables) in the environment. This work provides examples of the forest fire model and sandpile model as self-organizing systems in which the relaxation time successfully predicts the onset of large avalanches. Furthermore, the relaxation time can show a consistent with the increasing trend in both oscillatory and nonoscillatory bifurcations, suggesting that the relaxation time is more universal than traditional indirect metrics such as the variance and the lag-1 autocorrelation function. We aim to identify early warning signals before the onset of large avalanches and provide scientific evidence and significant information for managers to formulate mitigation countermeasures and strategic decisions.

The study of post-storm beach recovery is important for economic development and the protection of life in coastal areas. In this study, field observations were conducted for 21 days in the surf zone of Dongdao Beach, Hailing Island, China, after tropical storm “Cempaka”. Data on depth, wave, Eulerian velocity, sediment, three-dimensional topography of the beach, and high-frequency variations in bed-level elevation were collected. The results showed that the beach experienced medium- to low- to medium-energy waves during field observations and covered two complete astronomical tide cycles. Contrary to the effect of wave energy conditions on beaches under normal wave conditions, a higher wave energy during beach recovery can promote silting and accelerate beach recovery. Tidal water level is an important factor affecting beach restoration, and a smaller tidal range is conducive to beach accretion. In a mixed semidiurnal tide, beach erosion and accretion occurred in the “highest tide” and “sub-highest tide” tidal cycles, respectively, and the combined effect of the two affected the change in the bed level in a mixed semidiurnal tide. After the storm, the hydrodynamic forcing mechanism and self-organization process of the sand bar jointly drove the formation of the topography of the bar channel in the surf zone. After the storm stopped, the spectral energy in free surface elevation was mainly distributed in the very low frequency and decayed rapidly at the infragravity band. The very low-frequency pulsation of the surf zone during recovery is a prominent feature of bed-level elevation, depth, and velocity. This study provides a good case for the study of hydrodynamic and bed level changes in the post-storm surf zone, as well as a reference for future studies of the intrinsic mechanisms post-storm beach recovery processes around the world.

We investigate ratcheting heat flow in simple networks consisting of a one-dimensional nonlinear chain with a self-coupled loop when the average thermal bias is zero. The effects of coupling strength and temporally averaged environmental reference temperature on the ratcheting heat flow are discussed. It is found that the total heat flow (THF) will be reversed, while heat flow in the self-coupled loop will disappear with the increase of the coupling strength. A critical coupling strength exists at which the THF disappears, and heat flow exists in the self-coupled loop, i.e., eddy ratcheting heat flow displays. The underlining physical mechanisms are analyzed through phonon spectra and unsteady thermal wave dynamics. Furthermore, a reversal of the THF from a negative to a positive value can be controlled by increasing the reference temperature. A critical reference temperature exists at which the negative THF exhibits a maximum value. Phonons dominate the ratcheting heat flow in the self-coupled loop, while solitons dominate the THF for weak coupling strength. These results can possibly be realized in nanoscale experiments and will help to further understand the thermal information on coupled nanotubes, polymer chains, and biological networks.

Abstract Background To investigate hypothalamic-pituitary-thyroid function in children of different ages, nutritional phases, and genotypes that were diagnosed with Prader-Willi syndrome (PWS), as well as the effects of recombinant human growth hormone (rhGH) treatment on thyroid hormones in PWS patients. Methods One hundred and thirty PWS patients (87 boys and 43 girls) aged from newborn to 15 years (y) (median 1.25 y, mean, SD: 2.95 ± 3.45 y), were surveyed in this study. Serum thyroid hormone levels were examined at least once per3-6 months during the 2 years follow-up study. Central hypothyroidism (C-HT) was identified as low/normal thyroid-stimulating hormone (TSH) and low free thyroxine 4 (FT4). Results All study participants had normal neonatal TSH screening test results. The prevalence of C-HT is 36.2% (47/130). No C-HT cases were diagnosed in PWS either below 1 month (m) or above 12 y. The prevalence of C-TH would be increased with age before 3 y until reaching the peak, followed by a gradual decline over the years. The prevalence of C-HT varies significantly at different ages (Pearson's χ2 = 19.915; p

Abstract Background Allan-Herndon-Dudley syndrome (AHDS) is an X-linked recessive neurodegenerative disorder caused by mutations in the SLC16A2 gene that encodes thyroid hormone transporter. AHDS has been rarely reported in China. Case presentation This study reported a novel splicing mutation in the SLC16A2 gene in an 18-month-old male patient with AHDS. The patient was born to non-consanguineous, healthy parents of Chinese origin. He passed new-born screening for hypothyroidism, but failed to reach developmental milestones. He presented with hypotonia, severe mental retardation, dysarthria and ataxia. Genetic analysis identified a novel splicing mutation, NM_006517.4: c.431-2 A > G, in the SLC16A2 gene inherited from his mother. The patient received Triac treatment, (triiodothyroacetic acid), a thyroid hormone analogue for 3 months. Triac treatment effectively reduced serum TSH concentrations and normalized serum T3 concentrations in the patient. Conclusions This study reported the first case of AHDS treated by Triac in China. And the study expanded the mutational spectrum of the SLC16A2 gene in AHDS patients.

Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH).Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis.Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age.Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.

Abstract Background Serum ceruloplasmin is one of the major diagnostic parameters for Wilson’s disease (WD). Age and gender difference of serum ceruloplasmin remain controversy. This study aims to assess diagnostic value of serum ceruloplasmin level for WD in children up to age of 15 years. Methods Serum ceruloplasmin levels were measured in 317 WD patients, 21 heterozygotes, 372 healthy control children and 154 non-WD patients with other liver diseases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic accuracy of serum ceruloplasmin for WD in children. Results Among healthy controls, serum ceruloplasmin level was slightly low in the infants younger than 6 months, and then maintained from 26 to 33 mg/dl after age of 6 months. A total of 8.1% of healthy children had levels of serum ceruloplasmin 20 mg/dL. Serum ceruloplasmin levels had gender difference, being higher in healthy boys than healthy girls, and higher in asymptomatic WD boys than asymptomatic WD girls (p

Abstract Background Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized. Method Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described. Results Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only. Conclusions The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.

PurposeVitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by deficiency of the CYP27B1 gene. This study aims to investigate the phenotypic and genotypic features of VDDR1A children in southern China and evaluate the long-term therapeutic effects.MethodsTwelve children from southern China with VDDR1A were enrolled in this study. Their clinical, radiological, biochemical, and molecular findings were analyzed retrospectively. The rickets severity score (RSS), biochemical parameters, and height standard deviation score (HtSDS) were used to evaluate clinical outcomes.ResultsSix males and six females were included in this VDDR1A cohort. The age of onset was from 6 months to 1.8 years, and the age at diagnosis was 2.1 ± 0.8 years. The most common clinical symptoms at diagnosis were delayed walking (10/12) and severe growth retardation (9/12). HtSDS at diagnosis was negatively associated with age (p

Recently, massive efforts have been made to control phonon transport via introducing disorder. Meanwhile, materials informatics, an advanced material-discovery technology that combines data-driven search algorithms and material property simulations, has made significant progress and shown accurate prediction ability in studying the target properties of new materials. However, with the introduction of disorder, the design space of random structures is greatly expanded. Global optimization for the entire domain is nearly impossible with the current computer resource even when materials informatics reduces the design space to a few percent. Toward the goal of reducing design space, we investigate the effect of different types of disorders on phonon transport in two-dimensional graphene/hexagonal boron nitride heterostructure using non-equilibrium molecular dynamics simulation. The simulation results show that when the hexagonal boron nitride is distributed disorderly in the coherent phonon-dominated structure, that is, the structure with a period length of 1.23 nm, the thermal conductivity is significantly reduced due to the appearance of coherent phonon localization. By qualitatively analyzing different types of disorder, we found that the introduction of disordered structure in the cross direction with a larger shift distance can further reduce the thermal conductivity. Further physical mechanism analysis revealed that the structures with lower thermal conductivity were caused by weak propagation and strong localization of phonon. Our findings have implications for accelerating machine learning in the search for structures with the lowest thermal conductivity, and provide some guidance for the future synthesis of 2D heterostructures with unique thermal properties.

Thermoelectric (TE) technology, which can convert scrap heat into electricity, has attracted considerable attention. However, broader applications of TE are hindered by lacking high-performance thermoelectric materials, which can be effectively progressed by regulating the carrier concentration. In this work, a series of PbSe(NaCl)x (x = 3, 3.5, 4, 4.5) samples were synthesized through the NaCl salt-assisted approach with Na+ and Cl− doped into their lattice. Both theoretical and experimental results demonstrate that manipulating the carrier concentration by adjusting the content of NaCl is conducive to upgrading the electrical transport properties of the materials. The carrier concentration elevated from 2.71 × 1019 cm−3 to 4.16 × 1019 cm−3, and the materials demonstrated a maximum power factor of 2.9 × 10−3 W m−1 K−2. Combined with an ultralow lattice thermal conductivity of 0.7 W m−1 K−1, a high thermoelectric figure of merit (ZT) with 1.26 at 690 K was attained in PbSe(NaCl)4.5. This study provides a guideline for chemical doping to improve the thermoelectric properties of PbSe further and promote its applications.

One-dimensional (1D) chain models are frequently employed to investigate heat conduction in various systems. Despite their widespread use, there has been limited exploration of 1D chain models with anisotropic interactions. In this study, we examine heat conduction in a 1D chain model with orientation–position coupled interaction, namely the compressible XY model, and compare it with isotropic Fermi-Pasta-Ulam-Tsingou β (FPUT- β ) systems. At low temperatures, the local temperatures in the translational and rotational degrees of freedom differ due to the difference in the contact thermal resistance in the two degrees of freedom. The system maintains orientational order, and the orientation–position-coupling effect lowers thermal conductivity in translational degrees of freedom. As the temperature rises above a transition point, the rotation of particles switches from oscillation to diffusion, leading to a solid-like to fluid-like transition in the rotational degree of freedom. The anisotropic interactions become negligible under time averaging, making the system’s properties similar to those of isotropic FPUT- β systems. Additionally, we investigate the system’s orientational structure to elucidate this transition. These findings will enhance our understanding of the dynamics of nanoscale anisotropic systems, such as the heat conduction of spin chains.

Citrus Huanglongbing (HLB) is the most devastating disease of citrus caused by the Gram-negative phloem-limited bacterium “Candidatus Liberibacter asiaticus” (CLas). It can be transmitted by the Asian citrus psyllid “Diaphorina citri,” by grafting, and by the holoparasitic dodder. In this study, the non-natural host periwinkle (Catharanthus roseus) was infected via dodder (Cuscuta campestris) from CLas-infected citrus plants, and the asymptomatic leaves (AS) were subjected to transcriptomic and small-RNA profiling. The results were analyzed together with a transcriptome dataset from the NCBI repository that included leaves for which symptoms had just occurred (S) and yellowing leaves (Y). There were 3,675 differentially expressed genes (DEGs) identified in AS, and 6,390 more DEGs in S and further 2109 DEGs in Y. These DEGs were commonly enriched in photosystem, chloroplast, membrane, oxidation-reduction process, metal/zinc ion binding on GO. A total of 14,974 DEGs and 336 DE miRNAs (30 conserved and 301 novel) were identified. Through weighted gene co-expression network and nested network analyses, two critical nested miRNA–mRNA regulatory networks were identified with four conserved miRNAs. The primary miR164-NAC1 network is potentially involved in plant defense responses against CLas from the early infection stage to symptom development. The secondary network revealed the regulation of secondary metabolism and nutrient homeostasis through miR828-MYB94/miR1134-HSF4 and miR827-ATG8 regulatory networks, respectively. The findings discovered new potential mechanisms in periwinkle–CLas interactions, and its confirmation can be done in citrus–CLas system later on. The advantages of periwinkle plants in facilitating the quick establishment and greater multiplication of CLas, and shortening latency for disease symptom development make it a great surrogate for further studies, which could expedite our understanding of CLas pathogenesis.

Choroidal metastasis as an initial presenting feature of lung cancer with EML4-ALK translocation is exceedingly rare and greatly impacts patient quality of life (QOL). There are no recommended treatments for such patients, and palliative care remains limited. It is unclear whether surgical resection of primary pulmonary lesions, systemic antitumor therapy, targeted therapy, or localized ocular therapy are effective in treating choroidal metastases in EML4-ALK rearranged oligometastatic non-small cell lung cancer (NSCLC). Here, we present the case of choroidal metastases secondary to lung cancer and EML4-ALK translocation in a 57-year-old woman who firstly underwent resection of lung lesions followed by oral administration of crizotinib without local treatment or systemic chemotherapy. Since then she had a rapid and complete response to crizotinib with 27 months of progression-free survival.

Abstract Background Hajdu-Cheney syndrome (HCS) is a rare inherited skeletal disorder caused by pathogenic mutations in exon 34 of NOTCH2. Its highly variable phenotypes make early diagnosis challenging. In this paper, we report a case of early-onset HCS with severe phenotypic manifestations but delayed diagnosis. Case presentation The patient was born to non-consanguineous, healthy parents of Chinese origin. She presented facial anomalies, micrognathia and skull malformations at birth, and was found hearing impairment, congenital heart disease and developmental delay during her first year of life. Her first visit to our center was at 1 year of age due to cardiovascular repair surgery for patent ductus arteriosus (PDA) and ventricular septal defect (VSD). Skull X-ray showed wormian bones. She returned at 7 years old after she developed progressive skeletal anomalies with fractures. She presented with multiple wormian bones, acro-osteolysis, severe osteoporosis, bowed fibulae and a renal cyst. Positive genetic test of a de novo heterozygous frameshift mutation in exon 34 of NOTCH2 (c.6426dupT) supported the clinical diagnosis of HCS. Conclusion This is the second reported HCS case caused by the mutation c.6426dupT in NOTCH2, but presenting much earlier and severer clinical expression. Physicians should be aware of variable phenotypes so that early diagnosis and management may be achieved.

Objective:To explore the clinical presentation and molecular genetic characteristics of a cohort of congenital hyperinsulinism (CHI) patients from southern China and also to explore the most appropriate therapeutic approaches.Methods:We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was performed for KCNJ11 and ABCC8 genes. The GLUD1 gene was sequenced in patients with hyperammonaemia. GCK gene sequencing was performed in those patients with no mutation identified in the ABCC8, KCNJ11 or GLUD1 genes.Results:ABCC8 mutations were identified in 16 (25%) of the cohort, GLUD1 mutations were identified in five children, and no KCNJ11 or GCK mutations were identified. Moreover, some unique features of ABCC8 gene mutations in southern Chinese CHI patients were found in this study. The most common mutation was a deletion/insertion mutation p.Thr1042GlnfsX75 was found in five unrelated patients, which possibly represents a relatively common mutation in southern China. Five novel ABCC8 mutations were detected. The mutations were p.Phe5SerfsX72, p.Gln273ArgfsX85, p.Leu724del, p.Asp1447Gly and IVS 25-1G>T. Five compound heterozygous mutations of ABCC8 gene were identified in this study, and three of these patients were diazoxide-responsive. Forty patients were diazoxide-responsive, 13 patients were diazoxide-unresponsive and 12 patients received dietary treatment only. A pancreatectomy was performed in 10 patients who were unresponsive to medical treatment.Conclusion:To the best of our knowledge, this is the first study of CHI in south China. Mutations in ABCC8 are the most common causes of CHI in this cohort. Diazoxide and dietary treatment were effective in most patients. Multicentre studies are necessary to obtain the long-term follow-up characteristics of such patients at a national level.

Abstract Objective Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G > C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G > C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions In this study, six mutations in the ALPL gene were found in four Chinese HPP patients, two of which were novel: c.359G > C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G > C might be disease-causing and associated with severe infantile form of HPP.

Hypochlorous acid (HOCl) is a reactive substance that reacts with most biomolecules and is essential in physiological and pathological processes. Abnormally elevated HOCl levels may cause inflammation and other disease responses. To further understand its key role in inflammation, HOCl must be detected in situ. Here, we designed a hydroxytricyanopyrrole-based small-molecule fluorescent probe (HTCP-NTC) to monitor and identify trace amounts of HOCl in biological systems. In the presence of HOCl, HTCP-NTC released hydroxyl groups that emit strong fluorescence covering a wide wavelength range from the visible to near-infrared region owing to the resumption of the intramolecular charge transfer process. Additionally, HTCP-NTC demonstrated a 202-fold fluorescence enhancement accompanied by a large Stokes shift and a low detection limit (21.7 nM). Furthermore, HTCP-NTC provided a rapid response to HOCl within 18 s, allowing real-time monitoring of intracellular HOCl. HTCP-NTC exhibited rapid kinetics and biocompatibility, allowing effective monitoring of the exogenous and endogenous HOCl fluctuations in living cells. Finally, based on fluorescence imaging, HTCP-NTC is a potential method for understanding the relationship between inflammation and HOCl.

Background: Schizophrenia is a complex mental disorder resulting in poor life quality and high social and economic burden. Despite the fact that genome-wide association studies (GWASs) have successfully identified a number of risk loci for schizophrenia, identifying the causal genes at the risk loci and elucidating their roles in disease pathogenesis remain major challenges. Methods: The summary data-based Mendelian randomization analysis (SMR) was used to integrate a large-scale GWAS of schizophrenia with brain expression quantitative trait loci (eQTL) data and brain methylation expression quantitative trait loci (meQTL) data, to identify novel risk gene(s) for schizophrenia. We then analyzed the mRNA expression and methylation statuses of the gene hit BTN3A2 during the early brain development. Electrophysiological analyses of CA1 pyramidal neurons were performed to evaluate the excitatory and inhibitory synaptic activity after overexpression of BTN3A2 in rat hippocampal slices. Cell surface binding assay was used to test the interaction of BTN3A2 and neurexins. Findings: We identified BTN3A2 as a potential risk gene for schizophrenia. The mRNA expression and methylation data showed that BTN3A2 expression in human brain is highest post-natally. Further electrophysiological analyses of rat hippocampal slices showed that BTN3A2 overexpression specifically suppressed the excitatory synaptic activity onto CA1 pyramidal neurons, most likely through its interaction with the presynaptic adhesion molecule neurexins. Interpretation: Increased expression of BTN3A2 might confer risk for schizophrenia by altering excitatory synaptic function. Our result constitutes a paradigm for distilling risk gene using an integrative analysis and functional characterization in the post-GWAS era. Fund: This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 to Y-GY), the National Natural Science Foundation of China (31730037 to Y-GY), and the Bureau of Frontier Sciences and Education, Chinese Academy of Sciences (QYZDJ-SSW-SMC005 to Y-GY). Keywords: Schizophrenia, Integrative analysis, BTN3A2, Brain development, Glutamatergic synapse

Complex dynamical systems have tipping points and exhibit nonlinear dynamics. It is difficult to predict and prevent the onset and progression of the tumors, mainly due to the complexity of interactions between tumor growth and tumor-immune cells involved. Moreover, previous models were based on the influence of the zero-dimensional systems and did not consider the spatiotemporal fluctuation in the tumor microenvironment. We here extend the previous model to a two-dimensional system and employ spatial early warning signals to study the spatially extended tumor-immune system with stochasticity. On the one hand, we obtain the stationary probability density of the system under the mean-field approximation assumption. It is found that the health state gets more and more stable than the disease state as the noise level increases when the system has a bistable state, and the system goes from health to disease state through a bistable region as the growth rate increases. On the other hand, we present a spatiotemporal diffusion coefficient indicator to predict upcoming critical transitions. It is shown that a rising spatiotemporal diffusion coefficient obtained from the spatial snapshot data can be an effective indicator for predicting upcoming critical transitions. Anticipating critical transitions in the spatial tumor-immune system with stochasticity can be greatly helpful to prevent disease onset and progression, which may intercept abrupt shifts from health to disease state.

In view of the small sample size of combat ammunition trial data and the difficulty of forecasting the demand for combat ammunition, a Bayesian inference method based on multinomial distribution is proposed. Firstly, considering the different damage grades of ammunition hitting targets, the damage results are approximated as multinomial distribution, and a Bayesian inference model of ammunition demand based on multinomial distribution is established, which provides a theoretical basis for forecasting the ammunition demand of multigrade damage under the condition of small samples. Secondly, the conjugate Dirichlet distribution of multinomial distribution is selected as a prior distribution, and Dempster–Shafer evidence theory (D-S theory) is introduced to fuse multisource previous information. Bayesian inference is made through the Markov chain Monte Carlo method based on Gibbs sampling, and ammunition demand at different damage grades is obtained by referring to cumulative damage probability. The study result shows that the Bayesian inference method based on multinomial distribution is highly maneuverable and can be used to predict ammunition demand of different damage grades under the condition of small samples.

A series of CeO2 based materials are analyzed using first-principles calculation. After geometry optimization, the calculated parameter of Ce32O64 is in good agreement with the experimental and theoretical results. The lattice constant of doped materials becomes increasingly smaller with the introduction of more Fe doping into the lattice owing to the small radii of impurity atoms. Other data relate to increase or decrease to some extent. As for electronic property, the energy band structure and partial density of states are explored and discussed. Due to the enhancement of the degree of hybridization between O atoms and metal atoms, there is a narrower band gap in Fe doped materials, indicating that lower energy can promote and achieve electronic transition from the valence band to the conduction band. Through the complex dielectric function composed of the real part and the imaginary part, the extinction coefficient, it is observed that they are responsive to light and electronic transition under visible light irradiation. On the other hand, we predict the photocatalytic behavior by discussing the extinction coefficient. Besides, the optical absorption spectrum and optical band gap are analyzed to further observe performance in photocatalysis. It is found that doping causes first the red shift of the absorption edge and then results in the red shift and enhancement of photocatalytic performance, which is consistent with our prediction. In addition, Eopt indicates that Fe is beneficial for the activity of CeO2. The atomic number ratio of 3:1 (Fe:Ce) shows superior behavior compared to other materials.

Abstract Background Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations. Methods We generated and characterized a mouse model (Fam83hTr/Tr) expressing a truncated FAM83H protein (amino acids 1–296), which recapitulated the ADHCAI‐causing human FAM83H p.Tyr297* mutation. Results Day 14 and 7‐week Fam83hTr/Tr molars exhibited rough enamel surfaces and slender cusps resulting from hypoplastic enamel defects. The lateral third of the Fam83hTr/Tr incisor enamel layer was thinner, with surface roughness and altered enamel rod orientation, suggesting disturbed enamel matrix secretion. Regular electron density in mandibular incisor enamel indicated normal enamel maturation. Only mildly increased posteruption attrition of Fam83hTr/Tr molar enamel was observed at 7‐weeks. Histologically, the Fam83hTr/Tr enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas. Conclusions Considering Fam83h−/− mice showed no enamel phenotype, while Fam83hTr/Tr (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.

Abstract Lake eutrophication ecosystems tend to exhibit bistable kinetics with two preferential configurations of oligotrophic and eutrophic states, and perturbations in the environmental parameters can cause regime shifts between two alternative stable states, yielding catastrophic regime shifts. In this article, we study stochastic kinetics of regime shifts in a time‐delayed lake eutrophication ecological system, where the environmental parameters are assumed to be disturbed by both input and loss external noises. The dynamical behavior of stochastic delay on the regime shifts between oligotrophic and eutrophic states is analyzed using numerical simulations. Time delays in loss and recycling processes are considered. It is shown from time series and probability distribution that noises and delays can induce regime shifts between two stable states. Theoretical analyses are used to support our numerical simulations. By using the mean first passage time (MFPT) technique, we also discuss the escape time problem between two stable states in time‐delayed ecosystems. A detailed study of the MFPT depending on various noise characteristics is performed, and the main results are compared for different cases of time delays.