A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Directional emission of a three-dimensional connection-type metamaterial.

Directional emission of electromagnetic waves plays an essential role in laser radar and free-space communication. For most directional antennas, bandwidth and miniaturization are a pair of contradictions due to their underlying interference mechanism. Connection-type metamaterials exhibit exotic electromagnetic response near zero-frequency, which relies on the global topology of mesh connectivity rather than resonance and thus has a broad working bandwidth. In this Letter, we investigate the broadband orientation-dependent coupling effect of a 3D double mesh metamaterial. Based on this effect, we achieve a broadband directional emission (relative bandwidth of 37.72%) using a compact structure (compared to twice working wavelength). Our work provides a novel, to the best of our knowledge, scheme to manipulate a long-wavelength wave and may pave the way to a miniaturized directional antenna.

Influence of annealing pretreatment in different atmospheres on crystallization quality and UV photosensitivity of gallium oxide films.

Due to their high wavelength selectivity and strong anti-interference capability, solar-blind UV photodetectors hold broad and important application prospects in fields like flame detection, missile warnings, and secure communication. Research on solar-blind UV detectors for amorphous Ga2O3 is still in its early stages. The presence of intrinsic defects related to oxygen vacancies significantly affects the photodetection performance of amorphous Ga2O3 materials. This paper focuses on growing high quality amorphous Ga2O3 films on silicon substrates through atomic layer deposition. The study investigates the impact of annealing atmospheres on Ga2O3 films and designs a blind UV detector for Ga2O3. Characterization techniques including atomic force microscopy (AFM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) are used for Ga2O3 film analysis. Ga2O3 films exhibit a clear transition from amorphous to polycrystalline after annealing, accompanied by a decrease in oxygen vacancy concentration from 21.26% to 6.54%. As a result, the response time of the annealed detector reduces from 9.32 s to 0.47 s at an external bias of 10 V. This work demonstrates that an appropriate annealing process can yield high-quality Ga2O3 films, and holds potential for advancing high-performance solar blind photodetector (SBPD) development.

Development and external validation of a nomogram for the early prediction of acute kidney injury in septic patients: a multicenter retrospective clinical study.

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Rapid classification of whole milk powder and skimmed milk powder by laser-induced breakdown spectroscopy combined with feature processing method and logistic regression.

Whole milk powder and skimmed milk powder are suitable for different groups of people due to their differences in composition. Therefore, a rapid classification method for whole milk powder and skimmed milk powder is urgently needed. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) and feature processing methods combined with logistic regression (LR) was constructed for the classification of milk powder. A LR classification model based on mini-batch gradient descent (MGD) was employed first. As indicated by the research results, the accuracy of the MGD-LR model for the milk powder samples in the test set is 96.33% and the modeling time is 33.07 s. The modeling efficiency is low and needs to be improved. Principal components analysis (PCA) and mutual information (MI) were used as feature processing methods to reduce the high dimensional LIBS data into fewer features for improving the modeling efficiency of the classification model. The research results indicate that the accuracy of the PCA-MGD-LR model and the MI-MGD-LR model for the test set of milk powder samples was 99.33% and 99.67%, respectively. Compared with MGD-LR model, the modeling efficiency of PCA-MGD-LR and MI-MGD-LR models has increased by 89.7% and 74.8%, respectively. The results fully demonstrate the feasibility of rapid milk powder classification based on LIBS and feature processing methods combined with LR, and it will provide a new technology for the identification and classification of milk powder.

Exceptional piezocatalytic H2 production of nitrogen-doped TiO2@carbon nanosheets induced by engineered piezoelectricity.

Piezocatalytic hydrogen evolution is a promising strategy to generate sustainable energy. In this report, nitrogen-doped (N-doped) TiO2@ carbon nanosheets (N-TiO2@C NSs) was successfully synthesized using C3N4 as a multifunctional template. During the synthesis, the two-dimensional (2D) architecture of C3N4 nanosheets directed the synthesis of TiO2 nanosheets. In addition, nitrogens of C3N4 were doped into the TiO2 lattice. Simultaneously, C3N4 was transformed into N-doped carbon nanosheets. N doping broke the crystal symmetry of TiO2, which endowed TiO2 with promising piezoelectric properties. The N-doped carbon nanosheets derived from C3N4 improved charge carrier separation efficiency and served as a flexible support to inhibit structural damage under sonication. Therefore, the N-TiO2@C NSs exhibited highly efficient activity for piezocatalytic H2 production (6.4 mmol·g-1·h-1) in the presence of methanol, much higher than those of the previously reported piezocatalysts. Our method is hoped to provide a new strategy for designing highly efficient piezocatalysts.

Second Chern crystals with inherently non-trivial topology.

Chern insulators have been generalized to many classical wave systems and thereby lead to many potential applications such as robust waveguides, quantum computation and high-performance lasers. However, the band structure of a material can be either topologically trivial or non-trivial, depending on how the crystal structure is designed. Here, we propose a second Chern crystal in a four-dimensional parameter space by introducing two extra synthetic translation dimensions. Since the topology of the bulk bands in the synthetic translation space is intrinsically non-trivial, our proposed four-dimensional crystal is guaranteed to be topologically non-trivial regardless of the crystal's detailed configuration. We derive the topologically protected modes on the lower dimensional boundaries of such a crystal via dimension reduction. Remarkably, we observe the one-dimensional gapless dislocation modes and confirm their robustness in experiments. Our findings provide novel perspectives on topologically non-trivial crystals and may inspire designs of classical wave devices.

Neuroprotective effect of engineered Clostridiumbutyricum-pMTL007-GLP-1 on Parkinson's disease mice models via promoting mitophagy.

Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.

Selective adsorption of trace morpholine impurities over N-ethyl morpholine by tetralactam solids.

The separation and especially the removal of morpholine (MOR) impurities from N-ethyl morpholine (NEM) is of great significance in the fine chemical industry. Herein, we offer a novel strategy for the selective adsorption of MOR over NEM by tetralactam solids. The adsorbent realized the purification of NEM by adsorbing traces of MOR impurities, such that the purity can be improved from around 98% to over 99.5%. Single crystal structures indicate that N-H⋯O and N-H⋯N hydrogen bonding interactions are essential in the selective separation.

Antichiral surface states in time-reversal-invariant photonic semimetals.

Besides chiral edge states, the hallmark of quantum Hall insulators, antichiral edge states can exhibit unidirectional transport behavior but in topological semimetals. Although such edge states provide more flexibility for molding the flow of light, their realization usually suffers from time-reversal breaking. In this study, we propose the realization of antichiral surface states in a time-reversal-invariant manner and demonstrate our idea with a three-dimensional (3D) photonic metacrystal. Our system is a photonic semimetal possessing two asymmetrically dispersed Dirac nodal lines. Via dimension reduction, the nodal lines are rendered a pair of offset Dirac points. By introducing synthetic gauge flux, each two-dimensional (2D) subsystem with nonzero kz is analogous to a modified Haldane model, yielding a kz-dependent antichiral surface transport. Through microwave experiments, the bulk dispersion with asymmetric nodal lines and associated twisted ribbon surface states are demonstrated in our 3D time-reversal-invariant system. Although our idea is demonstrated in a photonic system, we propose a general approach to realize antichiral edge states in time-reversal-invariant systems. This approach can be easily extended to systems beyond photonics and may pave the way for further applications of antichiral transport.

Engineered probiotics Clostridium butyricum-pMTL007-GLP-1 improves blood pressure via producing GLP-1 and modulating gut microbiota in spontaneous hypertension rat models.

Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon-like peptide-1 receptor (GLP-1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP-1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP-1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum-pMTL007-GLP-1 (CB-GLP-1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB-GLP-1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, ß-MHC, α-SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high-throughput sequencing further demonstrated that CB-GLP-1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB-GLP-1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.

Reactions of Thorium Oxide Clusters with Water: The Effects of Oxygen Content.

Thorium oxide has many important applications in industry. In this article, theoretical calculations have been carried out to explore the hydrolysis reactions of the ThOn (n=1-3) clusters. The reaction mechanisms of the O-deficient ThO and the O-rich ThO3 are compared with the stoichiometric ThO2 . The theoretical results show good agreement with the prior experiments. It is shown that the hydrolysis mainly occurred on the singlet potential surface. The overall reactions consist of two hydrolysis steps which are all favourable in energy. The effects of oxygen content on the hydrolysis are elucidated. Interestingly, among them, the peroxo group O2 2- in ThO3 is converted to the HOO- ligand, behaving like the terminal O2- in the hydrolysis which is transformed into the HO- groups. In addition, natural bond orbital (NBO) analyses were employed to further understand the bonding of the pertinent species and to interpret the differences in hydrolysis.

Anti-Tumor Effects of Engineered VNP20009-Abvec-Igκ-mPD-1 Strain in Melanoma Mice via Combining the Oncolytic Therapy and Immunotherapy.

Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors are the most promising treatments for malignant tumors currently, but the low response rate limits their further clinical utilization. To address this problem, our group constructed an engineered strain of VNP20009-Abvec-Igκ-mPD-1 [V-A-mPD-1 (mPD-1, murine PD-1)] to combine oncolytic bacterial therapy with immunotherapy. Further, we evaluated its growth performance and mPD-1 expression ability in vitro while establishing the melanoma mice model to explore its potential anti-cancer effects in tumor therapy. Our results indicated that the V-A-mPD-1 strain has superior growth performance and can invade B16F10 melanoma cells and express PD-1. In addition, in the melanoma mice model, we observed a marked reduction in tumor volume and the formation of a larger necrotic area. V-A-mPD-1 administration resulted in a high expression of mPD-1 at the tumor site, inhibiting tumor cell proliferation via the down-regulation of the expression of rat sarcoma (Ras), phosphorylated mitogen-activated protein kinase (p-MEK)/MEK, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK expression significantly inhibited tumor cell proliferation. Tumor cell apoptosis was promoted by down-regulating phosphoinositide 3 kinase (PI3K) and protein kinase B (AKT) signaling pathways, as evidenced by an increased Bcl-2-associated X protein/B cell lymphoma-2 (Bax/Bcl-2) expression ratio. Meanwhile, the expression levels of systemic inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), were substantially reduced. In conclusion, our research demonstrated that V-A-mPD-1 has an excellent anti-tumor effect, prompting that the combined application of microbial therapy and immunotherapy is a feasible cancer treatment strategy.

Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure.

BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive. METHODS: In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia. RESULTS: The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist. CONCLUSIONS: Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.

Long non-coding RNA SNHG16 decreased SMAD4 to induce gemcitabine resistance in pancreatic cancer via EZH2-mediated epigenetic modification.

Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine-resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine-resistant PC cells (PANC-1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild-type PC cells and in gemcitabine-resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p-Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation-quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p-Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2-mediated epigenetic modification.

Straight Photonic Nodal Lines with Quadrupole Berry Curvature Distribution and Superimaging "Fermi Arcs".

In periodic systems, nodal lines are loops in the three-dimensional momentum space with each point on them representing a band degeneracy. Nodal lines exhibit rich topological features, as they can take various configurations such as rings, links, chains, and knots. These line nodes are generally protected by mirror or PT symmetry and frequently accompanied by drumhead surface states. Here, we propose and demonstrate a novel type of photonic straight nodal lines in a D_{2D} metacrystal, which are protected by an unusual rotoinversion time (roto-PT) symmetry. These nodal lines are located at the central axis and hinges of the Brillouin zone. They appear as quadrupole sources of Berry curvature flux in contrast to the Weyl points, which are monopoles. Interestingly, topological surface states exist at all three cutting surfaces, as guaranteed by π-quantized Zak phases along all three directions. As frequency changes, the surface state equifrequency contours evolve from closed to open and become straight lines at a critical transition frequency, at which diffractionless surface wave propagations are experimentally demonstrated, paving the way toward development of superimaging topological devices.

Establishment of a novel risk score for in-hospital mortality in adult sepsis patients.

Background: Existing scoring systems have limitations in predicting the in-hospital mortality of adult sepsis patients. We aimed to develop and validate a novel risk score for predicting the in-hospital mortality of adult sepsis patients. Methods: The clinical data of 1,335 adult sepsis inpatients were retrospectively analyzed. Enrolled patients were randomly divided into a modeling group and a validation group at a 3:2 ratio. The modeling group (n=801) was used to develop the risk score by univariate and multivariate logistic regression analyses. The score's performance was validated in the validation group (n=534). We classified patients into four risk levels according to the novel risk score. Results: Age, central vein catheterization, mechanical ventilation, vasopressin, Charlson comorbidity index (CCI), respiratory rate (RR), heart rate (HR), Glasgow coma scale (GCS) score, platelet (PLT), hematocrit (HCT), aspartate aminotransferase (AST), and activated partial thrombin time (APTT) were independent risk factors for in-hospital death in adult sepsis patients. Continuous variables were converted into classified variables to develop the risk score, with a total score of 39 points. Adult sepsis patients with low, lower medium, higher medium, and high risk levels had in-hospital mortality rates of 9.8%, 24.7%, 55.8%, and 83.5%, respectively. Conclusions: Compared with the Acute Physiology and Chronic Health Evaluation II scoring system (APACHE II) and the Modified Early Warning Score (MEWS), the novel risk score showed good predictive performance for in-hospital mortality in adult sepsis patients.

Palladium decoration directed synthesis of ZIF-8 nanocubes with efficient catalytic activity for nitrobenzene hydrogenation.

A palladium precursor (H2PdCl4) has been utilized as a novel structure-directing agent for controlling the morphology of ZIF-8. Using reverse micelles as nanoreactors, the Pd/ZIF-8 nanocomposite with a uniform size distribution is obtained. It is revealed that Pd(II) can selectively coordinate with the (100) plane of ZIF-8. As a result, the morphology of ZIF-8 is transformed from rhombic dodecahedral to cubic. After hydrogen treatment, the as-obtained Pd NPs/ZIF-8 nanocubes show efficient catalytic activity for nitrobenzene hydrogenation, which is higher than that of the commercially available Pd/C catalyst.

Evolutionary patterns of plastome resolve multiple origins of the Ns-containing polyploid species in Triticeae.

Tracing evolutionary history proves challenging for polyploid groups that have evolved rapidly, especially if an ancestor of a polyploid is extinct. The Ns-containing polyploids are recognized as the NsXm and StHNsXm genomic constitutions in Triticeae. The Ns originated from Psathyrostachys, while the Xm represented a genome of unknown origin. Here, we use genetic information in plastome to trace the complex lineage history of the Ns-containing polyploid species by sampling 26 polyploids and 90 diploid taxa representing 23 basic genomes in Triticeae. Phylogenetic reconstruction, cluster plot of genetic distance matrix, and migration event demonstrated that (1) the Ns plastome originated from different Psathyrostachys species, and the Xm plastome may originate from an ancestral lineage of Henrardia, Agropyron, and Eremopyrum; (2) the Ns, Xm, and St genome donors separately served as the maternal parents during the speciation of the Ns-containing polyploid species, resulting in a maternal haplotype polymorphism; (3) North AmericanLeymusspecies might originate from colonization during late Miocene via the Bering land bridge and were the paternal donor of the StHNsXm genome Pascopyrum species. Our results shed new light on our understanding of the rich diversity and ecological adaptation of the Ns-containing polyploid species.

[Probiotics' Ameliorating Effect on Side Effects of Cancer Treatment: Reflections and Prospects].

Surgical resection, radiotherapy, chemotherapy, and immunotherapy are the main therapies for cancers. These cancer therapies all prolong patient survival, but also bring multiple side effects. Gut microbiota participates in almost all the physiological and biochemical processes of the host, playing a key role in human health and diseases. As an exogenous intervention, probiotics can prevent diseases and enhance immunity. Their anti-cancer ability and ameliorative effect have received increasing recognition. Herein, we reported the latest findings on gut microbiota and cancer pathogenesis, focusing on the application of probiotics in reducing the side effects caused by cancer therapies and hoping to provide supportive references for the clinical use of probiotics in cancer treatment.