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Context Ulcerative colitis (UC) is an intractable inflammatory bowel disease that threatens the health of patients. The limited availability of therapeutic strategies makes it imperative to explore more efficient and safer drugs. Indigo naturalis (IN) is a traditional Chinese medicine that possesses many pharmacological activities, including anti-inflammatory, antioxidant, and immunomodulatory activities. The treatment potential of IN for UC has been proven by numerous preclinical and clinical studies in recent years.Objective This article provides a comprehensive review of the utility and potential of IN in the treatment of UC.Methods ‘Indigo naturalis’ ‘Qing dai’ ‘Qingdai’ ‘Ulcerative colitis’ and ‘UC’ are used as the keywords, and the relevant literature is collected from online databases (Elsevier, PubMed, and Web of Science).Results and Conclusion Indirubin, indigo, isatin, tryptanthrin, and β-sitosterol are considered the key components in the treatment of UC with IN. Both preclinical and clinical studies support the efficacy of IN for UC, especially in severe UC or in those who do not respond to or have poor efficacy with existing therapies. The mechanisms of IN for UC are associated with the aryl hydrocarbon receptor pathway activation, immune regulation, oxidative stress inhibition, and intestinal microbial modulation. However, the clinical use of IN has the risks of adverse events such as pulmonary hypertension, which suggests the necessity for its rational application. As a potential therapeutic agent for UC that is currently receiving more attention, the clinical value of IN has been initially demonstrated and warrants further evaluation.

Abstract Background Approximately 25–30% of patients with acute myeloid leukemia (AML) have FMS-like receptor tyrosine kinase-3 (FLT3) mutations that contribute to disease progression and poor prognosis. Prolonged exposure to FLT3 tyrosine kinase inhibitors (TKIs) often results in limited clinical responses due to diverse compensatory survival signals. Therefore, there is an urgent need to elucidate the mechanisms underlying FLT3 TKI resistance. Dysregulated sphingolipid metabolism frequently contributes to cancer progression and a poor therapeutic response. However, its relationship with TKI sensitivity in FLT3-mutated AML remains unknown. Thus, we aimed to assess mechanisms of FLT3 TKI resistance in AML. Methods We performed lipidomics profiling, RNA-seq, qRT-PCR, and enzyme-linked immunosorbent assays to determine potential drivers of sorafenib resistance. FLT3 signaling was inhibited by sorafenib or quizartinib, and SPHK1 was inhibited by using an antagonist or via knockdown. Cell growth and apoptosis were assessed in FLT3-mutated and wild-type AML cell lines via Cell counting kit-8, PI staining, and Annexin-V/7AAD assays. Western blotting and immunofluorescence assays were employed to explore the underlying molecular mechanisms through rescue experiments using SPHK1 overexpression and exogenous S1P, as well as inhibitors of S1P2, β-catenin, PP2A, and GSK3β. Xenograft murine model, patient samples, and publicly available data were analyzed to corroborate our in vitro results. Results We demonstrate that long-term sorafenib treatment upregulates SPHK1/sphingosine-1-phosphate (S1P) signaling, which in turn positively modulates β-catenin signaling to counteract TKI-mediated suppression of FLT3-mutated AML cells via the S1P2 receptor. Genetic or pharmacological inhibition of SPHK1 potently enhanced the TKI-mediated inhibition of proliferation and apoptosis induction in FLT3-mutated AML cells in vitro. SPHK1 knockdown enhanced sorafenib efficacy and improved survival of AML-xenografted mice. Mechanistically, targeting the SPHK1/S1P/S1P2 signaling synergizes with FLT3 TKIs to inhibit β-catenin activity by activating the protein phosphatase 2 A (PP2A)-glycogen synthase kinase 3β (GSK3β) pathway. Conclusions These findings establish the sphingolipid metabolic enzyme SPHK1 as a regulator of TKI sensitivity and suggest that combining SPHK1 inhibition with TKIs could be an effective approach for treating FLT3-mutated AML.

Abstract Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN’ enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury. Graphical Abstract

To improve the mechanical properties of casting aluminum-copper alloy, the mixed rare earth (RE) was added to ZL206 and its properties and the enhanced mechanism of alloy were researched. The results showed that the strength and hardness of the composite were improved by 10.2% and 6.2%, respectively. After adding mixed RE, which was led by the heterogeneous enrichment area blocking the growth of the α-Al phase and making grain refinement during the solidification process. The simulation results of RE surface adsorption models by first principles also showed that the elastic constant calculation improved the bulk modulus, shear modulus, and Young's modulus of the material. The addition of mixed RE enhances the strength and hardness, although it adversely affects toughness and reduces the machining index. Also, the work function decreased, and the Fermi level increased, reflecting that the electron locality on each band was strong and the bonding state of the alloy system was covalent, which showed that the corrosion resistance was enhanced after adding mixed RE. It provides a new method for the mechanism of RE-modified aluminum-copper alloys and expands the direction of cast aluminum-copper alloy modification.

Abstract Taking advantage of the high specific surface area of the nanoparticles, boron nitride (BN) nanoparticles were incorporated into the semi-solidified aluminium-copper alloy Al–5Cu–Mn (ZL201) system during the casting process, and its properties and enhancement mechanism were studied. The results shown that the BN in the new composite material is more uniformly distributed in the second phase (Al2Cu), which can promote grain refinement and enhance the bonding with the aluminium-based interface, and the formation of stable phases such as AlB2, AlN, CuN, etc. makes the tensile strength and hardness of the material to be significantly improved (8.5%, 10.2%, respectively). The mechanism of the action of BN in Al2Cu was analyzed by establishing an atomic model and after calculation: BN can undergo strong adsorption on the surface of Al2Cu (0 0 1), and the adsorption energy is lower at the bridge sites on the two cut-off surfaces, which makes the binding of BN to the aluminum base more stable. The charge transfer between B, N and each atom of the matrix can promote the formation of strong covalent bonds Al–N, Cu–N and Al–B bonds, which can increase the dislocation density and hinder the grain boundary slip within the alloy.

Abstract Background Nucleophosmin 1 (NPM1) gene‐mutated acute myeloid leukemia (NPM1mut AML) is classified as a subtype with a favorable prognosis. However, some patients fail to achieve a complete remission or relapse after intensified chemotherapy. Genetic abnormalities in concomitant mutations contribute to heterogeneous prognosis of NPM1mut AML patients. Methods In this study, 91 NPM1‐mutated and FLT3‐ITD wild‐type (NPM1mut/FLT3‐ITDwt) AML patients with intermediate‐risk karyotype were enrolled to analyze the impact of common genetic co‐mutations on chemotherapeutic outcome. Results Our data revealed that TET1/2 (52/91, 57.1%) was the most prevalent co‐mutation in NPM1mut AML patients, followed by IDH1/2 (36/91, 39.6%), DNMT3A (35/91, 38.5%), myelodysplastic syndrome related genes (MDS‐related genes) (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 genes) (35/91, 38.5%), FLT3‐TKD (27/91, 29.7%) and GATA2 (13/91, 14.3%) mutations. Patients with TET1/2mut exhibited significantly worse relapse‐free survival (RFS) (median, 28.7 vs. not reached (NR) months; p = 0.0382) compared to patients with TET1/2wt, while no significant difference was observed in overall survival (OS) (median, NR vs. NR; p = 0.3035). GATA2mut subtype was associated with inferior OS (median, 28 vs. NR months; p

The digital correlator is one of the most crucial data processing components of a radio telescope array. With the scale of radio interferometeric array growing, many efforts have been devoted to developing a cost-effective and scalable correlator in the field of radio astronomy. In this paper, a 192-input digital correlator with six CASPER ROACH2 boards and seven GPU servers has been deployed as the digital signal processing system for Tianlai cylinder pathfinder located in Hongliuxia observatory. The correlator consists of 192 input signals (96 dual-polarization), 125-MHz bandwidth, and full-Stokes output. The correlator inherits the advantages of the CASPER system, for example, low cost, high performance, modular scalability, and a heterogeneous computing architecture. With a rapidly deployable ROACH2 digital sampling system, a commercially expandable 10 Gigabit switching network system, and a flexible upgradable GPU computing system, the correlator forms a low-cost and easily-upgradable system, poised to support scalable large-scale interferometeric array in the future.

Hall thrusters are electric propulsion devices that are widely used in modern spaceflight. To obtain the critical corrosion data effectively and accurately during long-life tests of Hall thrusters, this paper proposes an automated corrosion measurement method based on three-dimensional point cloud technology. This method uses binocular structured light scanning method to obtain surface point cloud data. The point cloud topology relationship of these disordered data is also established by KD-tree and radius filtering. The base plane is determined according to the average of the outer circle plane in the discharge chamber, and the original point cloud data is sliced transversely and longitudinally. The point cloud of section data is extracted and the corrosion width data is obtained according to the round hole feature extraction and center of circle calculation. The corrosion angle is calculated according to the angle between the straight line and the normal of the section. The proposed method has been verified and the results show that the overall error accuracy is within 60 μm, which meets the requirements for automatic measurement of Hall thruster corrosion. It is a real and effective method to obtain the critical corrosion data during long-life tests of Hall thrusters.

Abstract Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems’ complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Abstract Background Alterations in the intestinal microbiota may play a role in the pathogenesis of functional bowel disorders (FBDs). Probiotics are widely used to improve intestinal dysbacteriosis in FBDs. In the context of FBDs, washed microbiota transplantation (WMT) appear to be a promising therapeutic option. We aimed to compare probiotics with WMT by using a propensity-score matching analysis (PSMA). Methods We conducted a retrospective investigation of 103 patients with FBDs, including irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB). Patients were divided into the WMT group or probiotics group (taking probiotics capsules). Data on the following parameters were matched for PSMA: age; sex; disease course; body mass index; anxiety; insomnia; tobacco smoking; alcohol consumption; and levels of D-lactate, diamine oxidase, and lipopolysaccharide. Intestinal barrier function (IBF) and symptoms were evaluated both before and after treatment initiation. Prognostic factors were assessed by Cox proportional hazards regression analysis. Results PSMA identified in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group. Improvement of FBD symptoms was greater with WMT than probiotics (P = 0.002). The WMT group had significantly fewer patients with intestinal barrier damage than the probiotics group (38.2% vs. 67.6%, P = 0.041). This improvement of FBD with WMT was further reflected as a reduction in D-lactate levels (P = 0.031). Increased D-lactate levels which were identified as a prognostic factor for FBDs (HR = 0.248, 95%CI 0.093–0.666, P = 0.006) in multivariate Cox regression analysis. Conclusion WMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels in patients with FBDs may predict a favorable response to WMT treatment.

Robust and efficient multi-source image matching remains a challenging task due to nonlinear radiometric differences between image features. This paper proposes a pixel-level matching framework for multi-source images to overcome this issue. Firstly, a novel descriptor called channel features of phase congruency (CFPC) is first derived at each control point to create a pixelwise feature representation. The proposed CFPC is not only simple to construct but is also highly efficient and somewhat insensitive to noise and intensity changes. Then, a Fast Sequential Similarity Detection Algorithm (F-SSDA) is proposed to further improve the matching efficiency. Comparative experiments are conducted by matching different types of multi-source images (e.g., Visible–SAR; LiDAR–Visible; visible–infrared). The experimental results demonstrate that the proposed method can achieve pixel-level matching accuracy with high computational efficiency.

In this paper, the structural, electronic, and elastic properties of Fe3SnC were calculated based on local density approximation (LDA) and generalized gradient approximation (GGA) in density functional theory (DFT). Compared with GGA, LDA underestimates lattice constants and overestimates binding energy and elastic constants. The calculated lattice constants are 3.76 Å (LDA) and 3.83 Å (GGA), respectively, and the latter is closer to the experimental values. With U correction in GGA and LDA, the magnetic properties of the system are shown in the band structure. The GGA calculation results are more accurate, and the calculated magnetic moment of Fe3SnC is 5.74μB. The band structure indicates that Fe3SnC is a metallic compound. The elastic constants show that Fe3SnC has a large elastic constant and bulk modulus, in which the C11 calculated by GGA is as high as 463.81GPa, and the Young's modulus is as high as 350.72GPa. This indicates that Fe3SnC is a potential cermet due to a strong deformation resistance. At the same time, with the minimum thermal conductivity of 1.65 W/mK calculated by the Cahill model.

Background: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). Methods: PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated. Results: The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds. Conclusion: Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.

Abstract Developing eco-friendly chiral organocatalysts with the combined advantages of homogeneous catalysis and heterogeneous processes is greatly desired. In this work, a family of amphiphilic one-handed helical polyisocyanides bearing phosphine pendants is prepared, which self-assembles into well-defined chiral micelles in water and showed thermo-responsiveness with a cloud point of approximately 38.4 °C. The micelles with abundant phosphine moieties at the interior efficiently catalyze asymmetric cross Rauhut-Currier reaction in water. Various water-insoluble substrates are transferred to target products in high yield with excellent enantioselectivity. The yield and enantiomeric excess (ee) of the product generated in water are up to 90% and 96%, respectively. Meanwhile, the yields of the same R-C reaction catalyzed by the polymer itself in organic solvents is

Abstract Background The recently developed Hybrid Hernia Repair technique (HHR), an adaptation of the laparoscopic method, has been proposed as a potential alternative for the treatment of complex Incisional Ventral Hernias (IVH). While single-arm studies have reported promising outcomes, a comprehensive meta-analysis affirming these benefits is lacking. This meta-analysis aims to compare the clinical outcomes of HHR and Laparoscopic Hernia Repair (LHR) in the management of IVH. Methods An exhaustive search of the literature was conducted, targeting publications in both English and Chinese that compare HHR and LHR up to March 31, 2023. The primary outcomes examined were operation time, blood loss, and intestinal injury. Secondary outcomes included rates of seroma, wound infection, post-operative acute/chronic pain, recurrence, and mesh bulging. The RevMan 5.0 software facilitated the statistical meta-analysis. Results The final analysis incorporated data from 14 studies, encompassing a total of 1158 patients, with 555 undergoing HHR and 603 treated with LHR. Follow-up data, ranging from 12 to 88 months, were available in 12 out of the 14 identified studies. The HHR method was associated with a significantly lower risk of seroma (OR = 0.29, P = 0.0004), but a higher risk of wound infection (OR = 2.10, P = 0.04). No significant differences were observed between the two techniques regarding operation time, blood loss, intestinal injury, intestinal obstruction, post-operative pain, mesh bulging, and recurrence. Conclusions The HHR technique did not demonstrate a clear advantage over LHR in reducing surgical complications, apart from a lower incidence of postoperative seroma. Surgeons with substantial expertise may choose to avoid incidental conversion or intentional hybrid procedures. Further research is needed to clarify the optimal surgical approach for IVH.

Abstract Background Platelet (PLT) count at diagnosis plays an important role in cancer development and progression in solid tumors. However, it remains controversial whether PLT count at diagnosis influences therapeutic outcome in patients with non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML). Methods This study analyzed the relationship between PLT count at diagnosis and genetic mutations in a cohort of 330 newly diagnosed non-APL AML patients. The impact of PLT count on complete remission, minimal residual disease status and relapse-free survival (RFS) were evaluated after chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results Our studies showed that patients with DNMT3A mutations have a higher PLT count at diagnosis, while patients with CEBPA biallelic mutations or t(8;21)(q22; q22) translocation had lower PLT count at diagnosis. Furthermore, non-APL AML patients with high platelet count (> 65 × 109/L) at diagnosis had worse response to induction chemotherapy and RFS than those with low PLT count. In addition, allo-HSCT could not absolutely attenuated the negative impact of high PLT count on the survival of non-APL AML patients. Conclusion PLT count at diagnosis has a predictive value for therapeutic outcome for non-APL AML patients.

In this paper, the elastic properties, chemical bonds, electronic properties, magnetic properties, and phonon spectra of CuNFe3 and CuNCo3 synthesized in the experiment are calculated by first principles. The results show they are ferromagnetic metal compounds with covalent and ionic bonds. CuNFe3 and CuNCo3 have large bulk modulus B, Young's modulus Y, and shear modulus G, which are 191.01 GPa, 202.33 GPa, 159.65 GPa, 247.01 GPa, 58.67 GPa and 95.26 GPa, respectively, which indicates that they have compressive solid resistance. The total magnetic moment of CuNFe3 is 6.96 μB, and that of CuNCo3 is 4.17 μB, which suggests that they have broad application prospects in magnetic storage, computer core, magnetic recording materials and other fields.

Laser-based direct energy deposition (DED-LB/M) has been a promising option for the surface repair of structural aluminum alloys due to the advantages it offers, including a small heat-affected zone, high forming accuracy, and adjustable deposition materials. However, the unequal powder particle size during powder-based DED-LB/M can cause unstable flow and an uneven material flow rate per unit of time, resulting in defects such as pores, uneven deposition layers, and cracks. This paper presents a multiscale, multiphysics numerical model to investigate the underlying mechanism during the powder-based DED-LB/M surface repair process. First, the worn surfaces of aluminum alloy components with different flaw shapes and sizes were characterized and modeled. The fluid flow of the molten pool during material deposition on the worn surfaces was then investigated using a model that coupled the mesoscale discrete element method (DEM) and the finite volume method (FVM). The effect of flaw size and powder supply quantity on the evolution of the molten pool temperature, morphology, and dynamics was evaluated. The rapid heat transfer and variation in thermal stress during the multilayer DED-LB/M process were further illustrated using a macroscale thermomechanical model. The maximum stress was observed and compared with the yield stress of the adopted material, and no relative sliding was observed between deposited layers and substrate components.

To further improve the mechanical properties of carbon nanotubes (CNTs) modified aluminum alloy (ZL105), the first principle was used to build the atomic structure of the alloy system and the alloy system was simulated by the VASP. After that, the heat treatment process of the cast aluminium alloy material with CNTs to enhance the alloy performance by the orthogonal experiment. The results of the research show that: (1) The energy status of the alloy system could be changed by adding the C atoms, but it did not affect the formation and structural stability of the alloy system, and the strong bond compounds formed by C atoms with other elements inside the solid solution structure can significantly affect the material properties. (2) The time of solid solution has the greatest influence on the performance of material that was modified by CNTs. The solution temperature and aging temperature were lower strength affection, and the aging time is the lowest affection. This paper provides a new research method of combining the atomic simulation with the casting experiment, which can provide the theoretical calculations to reduce the experiment times for the casting materials’ performance improvement.

The tightly focused structured light field displays a non‐negligible component of the electric field in the direction of propagation, i.e., the longitudinal light field. The longitudinal light field results in various novel optical phenomena, such as transverse spin angular momentum and 3D topological light fields. However, it remains a challenge to generate customized longitudinal light fields. Here, based on inverse design theory, the longitudinal light field can be customized on demand under the tightly focusing condition, which allows to generate the longitudinal light field with controllable structured distribution for propagating waves or manipulate the complex structures for all the three components of the electric field. In experiment, an experimental system is built integrating the generation, customization, and detection of structured longitudinal light field, and the customization of the longitudinal light fields with various patterns is experimentally realized. The customized longitudinal light field structures may find applications such as information encoding, long‐distance light manipulation, and novel light–matter interactions. As an example, information encoding is realized by the structured longitudinal light fields.

Abstract Background Neoadjuvant therapy favors the prognosis of various cancers, including esophagogastric junction cancer (EGC). However, the impacts of neoadjuvant therapy on the number of dissected lymph nodes (LNs) have not yet been evaluated in EGC. Methods We selected EGC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2006–2017). The optimal number of resected LNs was determined using X-tile software. Overall survival (OS) curves were plotted with the Kaplan–Meier method. Prognostic factors were evaluated using univariate and multivariate COX regression analyses. Results Neoadjuvant radiotherapy significantly decreased the mean number of LN examination compared to the mean number of patients without neoadjuvant therapy (12.2 vs. 17.5, P = 0.003). The mean LN number of patients with neoadjuvant chemoradiotherapy was 16.3, which was also statistically lower than 17.5 (P = 0.001). In contrast, neoadjuvant chemotherapy caused a significant increase in the number of dissected LNs (21.0, P 19 LNs had a better prognosis than those with 1–19 LNs (P 9 LNs had a better prognosis than those with 1–9 LNs (P

The diversity of neural stem cells is a hallmark of the cerebral cortex development in gyrencephalic mammals, such as Primates and Carnivora. Among them, ferrets are a good model for mechanistic studies. However, information on their neural progenitor cells (NPC), termed radial glia (RG), is limited. Here, we surveyed the temporal series of single-cell transcriptomes of progenitors regarding ferret corticogenesis and found a conserved diversity and temporal trajectory between human and ferret NPC, despite the large timescale difference. We found truncated RG (tRG) in ferret cortical development, a progenitor subtype previously described in humans. The combination of in silico and in vivo analyses identified that tRG differentiate into both ependymal and astrogenic cells. Via transcriptomic comparison, we predict that this is also the case in humans. Our findings suggest that tRG plays a role in the formation of adult ventricles, thereby providing the architectural bases for brain expansion.

Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7-positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers.

When rockfall occurs along dense rock slopes, the rotation direction of rockfall is not always downhill. Specifically, the rockfall may obtain a reverse rotation speed (RRS) after impact under certain conditions, the effect of which on the restitution coefficient (RC) cannot be ignored. According to the statistical results of the reverse rotation (RR) phenomena of blocks obtained from previous experiments, the occurrence of RR is correlated to the block shape, incident angle, and contact attitude. In this study, considering a typically shaped cubic block, the critical condition for the RR is preliminarily deduced. Based on the results, the influence of the RRS on the RC for four typically shaped blocks is examined using a customized device. Results show that the tangential RC (Rt) values of each block are not sensitive to the change in the RRS, the distribution is relatively concentrated and the values are high. Moreover, the normal RC (Rn) values are not sensitive to the RRS, and the distribution is relatively discrete. The RRS influences Rn; however, it is difficult to directly establish the relationship between them. To this end, considering the contact attitude and shape of the block, an integral variable, the impact coefficient (Ic), is proposed to determine the influence of RRS on Rn. Moreover, the impact-bounce behaviours of the block are categorized and analysed. For the block rebound following a single impact, Ic and Rn are positively and negatively correlated when the mass centre of the block (MC) is in front and behind the contact point (CP), respectively. For the block rebound following two successive impacts, with the increase in Ic, the Rn increases. These conclusions help clarify the mechanism of the influence of the RRS on RC and provide vital information and ideas for the development and optimization of a program to accurately predict rockfall trajectories.

Immobilizing organocatalysts onto helical polymers can facilitate catalyst recycling and boost enantioselectivity. Here, the authors prepare achiral organoiodine-functionalized single left- and right-handed helical polyisocyanides from the same monomers and demonstrate their use in three asymmetric oxidations.

The stability, electronic, optical and thermodynamic properties of X3OI (X = Na, K, Rb) have been calculated by first principles. The Birch-Murnaghan method was used to fit the optimal lattice constants of the three materials. The results show that the three compounds are stable and the calculated thermodynamic properties show that they conform to Dulong-Petit's law. They absorb light more strongly in the ultraviolet region and are direct bandgap semiconductors, which can be potential photodetector materials. Rb3OI has a band gap value of 1.69eV, which has the potential to be used as the absorption layer material for perovskite solar cells. The results provide a theoretical basis for further experimental study of these three materials.

Retinal injury after blunt ocular trauma may directly affect prognosis and lead to vision loss. To investigate the pathological changes and molecular mechanisms involved in retinal injury after blunt ocular trauma, we established a weight drop injury model of blunt ocular trauma in male Beagle dogs. Hematoxylin-eosin staining, immunofluorescence staining, western blotting, and TUNEL assays were performed to investigate retinal injury within 14 days after blunt ocular trauma. Compared with the control group, the thicknesses of the inner and outer nuclear layers, as well as the number of retinal ganglion cells, gradually decreased within 14 days after injury. The number of bipolar cells in the inner nuclear layer began to decrease 1 day after injury, while the numbers of cholinergic and amacrine cells in the inner nuclear layer did not decrease until 7 days after injury. Moreover, retinal cell necroptosis increased with time after injury; it progressed from the ganglion cell layer to the outer nuclear layer. Visual electrophysiological findings indicated that visual impairment began on the first day after injury and worsened over time. Additionally, blunt ocular trauma induced nerve regeneration and Müller glial hyperplasia; it also resulted in the recruitment of microglia to the retina and polarization of those microglia to the M1 phenotype. These findings suggest that necroptosis plays an important role in exacerbating retinal injury after blunt ocular trauma via gliosis and neuroinflammation. Such a role has important implications for the development of therapeutic strategies.

To provide a theoretical basis for the quality positioning, characteristic index screening and brand building of different grades of Yongchuan Xiuya, the active ingredients, color and taste performance of different grades of Yongchuan Xiuya products were analyzed. In this paper, the active ingredients’ content and L*, a*, b* color indexes of different grades of Yongchuan Xiuya products were detected, and the relationship between the characteristic indexes and grades was studied by principal component analysis (PCA); the taste characteristics of Yongchuan Xiuya products were analyzed by electronic tongue combined with sensory evaluation. The results showed that the active ingredients’ content of Yongchuan Xiuya product showed a certain trend with the change of product grade. It showed that with the decrease of product grade, the contents of tea polyphenols, water extracts and the ratio of phenol to amino acids were increased, while the contents of amino acids were decreased. And catechin (GC), epigallocatechin (EGC), catechin (C) content increased with the decrease of product grade. Four principal components were extracted by PCA analysis. And 16 characteristic indexes that have important contribution to quality were selected, including color indexes like dry tea L*, a*, b* value, fused leaf L*, b* value, chlorophyll a, chlorophyll b and total chlorophyll, and also tea polyphenols, amino acids, water extract, gallic acid (GA), GC, EGC, C, caffeine (CAF). And the score of PCA was opposite to the actual product grade ranking. The comprehensive score from high to low was: Level 6>Level 5>Level 4>Level 3>Level 2>Level 1. The taste of Yongchuan Xiuya with electronic tongue showed that with the decrease of product grade, the index values of sour taste, bitter taste and astringency gradually decreased, while the taste and richness increased. The three indexes include astringency aftertaste, umami and richness of electronic tongue had a extremely significant or significant negative correlation with the taste score and comprehensive score of reviewers (P

Nickel-63 radioactive sources used in micro nuclear batteries require high surface emissivity, thin coating and small substrate. The method for the preparation of nickel-63 radioactive sources by direct and constant current electrodeposition was established by using nickel-63 solution with small volume, high specific activity and low Ni2+ concentration as electrodeposition liquid.Using this method, under the conditions of copper substrate, Ni2+ concentration with 1 g/L, electrodeposition pH with 3.5-4.5 and sulphamic acid concentration with 0.1 g/L, the electrodeposition efficiency can reach to 95.8% after 1 h . The coating is compact and bright with the thickness from 0.3 μm to 1.6 μm. The surface emissivity of the prepared nickel-63 radio-source film is up to 2.40×107 s-1·(2πSr)-1 while the activity is up to 1.89×109 Bq, which can meet the application requirements of micro nuclear batteries. At the same time, by recovering the residual electrodeposition solution and adjusting its composition, the reuse of electrodeposition liquid is realized, reducing the waste of nickel-63 raw material.

Abstract Objective To investigate whether radiomics based on ultrasound images can predict lymphovascular invasion (LVI) of rectal cancer (RC) before surgery. Methods A total of 203 patients with RC were enrolled retrospectively, and they were divided into a training set (143 patients) and a validation set (60 patients). We extracted the radiomic features from the largest gray ultrasound image of the RC lesion. The intraclass correlation coefficient (ICC) was applied to test the repeatability of the radiomic features. The least absolute shrinkage and selection operator (LASSO) was used to reduce the data dimension and select significant features. Logistic regression (LR) analysis was applied to establish the radiomics model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the comprehensive performance of the model. Results Among the 203 patients, 33 (16.7%) were LVI positive and 170 (83.7%) were LVI negative. A total of 5350 (90.1%) radiomic features with ICC values of ≥ 0.75 were reported, which were subsequently subjected to hypothesis testing and LASSO regression dimension reduction analysis. Finally, 15 selected features were used to construct the radiomics model. The area under the curve (AUC) of the training set was 0.849, and the AUC of the validation set was 0.781. The calibration curve indicated that the radiomics model had good calibration, and DCA demonstrated that the model had clinical benefits. Conclusion The proposed endorectal ultrasound-based radiomics model has the potential to predict LVI preoperatively in RC.

Diazoacetate polymerizations using inexpensive catalysts has been a long-standing challenge to achieve. Here the authors report a Ni(II) catalyst that can promote living polymerization of various diazoacetates, yielding well-defined carbon–carbon main chain polymers, polycarbenes.

Ningxia province is a major coal-producing province in Northwest China that contributes significantly to China’s economic development. However, long-term coal mining in Ningxia province has brought many environmental issues, such as surface collapse, destruction of water resources, air pollution, and random stacking of waste coal gangue. Hence, promoting the coordinated development of coal mining and environmental protection and improving the overall level of green coal development have become two critical issues for the development of the coal industry in this region. According to the current situation of coal mining in Ningxia province, the technical problems that require immediate resolution, such as the bottleneck of basic theory and technology, imperfect technical standards and norms of green development, insufficient support of green development technique and equipment, and lack of demonstration guidance and policy support were summarized. Moreover, the strategic thought, development blueprint, and strategic objectives of green development of coal mines were put forward based on the realistic demand of future development of the coal industry in Ningxia province, forming the overall strategic layout in this region. On this basis, the technical paths for future green development of coal mines in Ningxia province were proposed from various perspectives, primarily water resources protection technology of coal mining, large-scale and low-cost treatment technology of mine water, surface ecological restoration technology of mining area, intelligent and green mining technology, and clean coal technology. Finally, some feasible suggestions for the green development of coal mines in Ningxia province were proposed. We should clarified the concept and goal of green development and actively implement green mining to promote the ecological environment and ecological civilization to a new level and realize the high-quality, sustainable development of the coal industry in Ningxia province.

Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage. Secondary damage presents the greatest challenge for medical staff; however, there are currently few effective therapeutic targets for secondary damage. Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system. Homer signaling can exert either positive or negative effects during such insults, depending on the specific subtype of Homer protein. Homer 1b/c couples with other proteins to form postsynaptic densities, which form the basis of synaptic transmission, while Homer1a expression can be induced by harmful external factors. Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells, mediated or affected by extracellular or intracellular signaling or cytoskeletal processes. This review summarizes the structural features, related signaling pathways, and diverse roles of Homer proteins in physiological and pathological processes. Upregulating Homer1a or downregulating Homer1b/c may play a neuroprotective role in secondary brain injuries. Homer also plays an important role in the formation of photoreceptor synapses. These findings confirm the neuroprotective effects of Homer, and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.

The temporal development of tissues and organs may be defined by the genome-wide epigenetic and transcriptional state functioning as the clock. Here the authors found that Fbl, a ribosomal RNA methyltransferase, potentially behaves as a clock during neural stem cell (NSC) development by controlling translational efficiencies of epigenetic modifiers in the cerebral cortex primordium.

BackgroundDespite previous research examining the predictive value of the geriatric nutritional risk index (GNRI) in individuals with urological cancers (UCs), results have been conflicting. This study aimed to comprehensively explore the potential link between GNRI and the prognosis of UCs using a meta-analysis.MethodsThe Cochrane Library, PubMed, Embase, and Web of Science databases were systematically and exhaustively searched. We estimated the prognostic importance of the GNRI in patients with UCs by calculating the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) on survival outcomes. Publication bias was identified using Egger’s test and Begg’s funnel plot.ResultsEight trials with 6,792 patients were included in our meta-analysis. Patients with UCs who had a lower GNRI before treatment had a higher risk of experiencing worse overall survival (HR = 2.62, 95% CI = 1.69–4.09, p < 0.001), recurrence-free survival/progression-free survival (HR = 1.77, 95% CI = 1.51–2.08, p < 0.001), and cancer-specific survival (HR = 2.32, 95% CI = 1.28–4.20, p = 0.006). Moreover, the subgroup analysis did not change the predictive significance of the GNRI in individuals with UCs. Neither Egger’s nor Begg’s test indicated substantial bias in this analysis.ConclusionAs a result of our meta-analysis, we found that a low GNRI strongly predicts poor prognosis for patients with UCs. A lower pretreatment GNRI indicates poor survival outcomes in UCs.

Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.

Abstract Background Drug-resistant tuberculosis (DR-TB) remains a major public health concern worldwide. Bedaquiline, a novel diarylquinoline, was added to the WHO-recommended all-oral regimen for patients with multidrug-resistant tuberculosis. We performed a systematic review and meta-analysis to determine the effect of bedaquiline on tuberculosis treatment outcomes. Methods We searched the PubMed, Web of Science and EMBASE databases for relevant studies published up to March 12, 2021. We included studies in which some participants received bedaquiline and others did not. Stata version 16.0 (Stata Corp., College Station, Texas, USA) was used to analyze the results of the meta-analysis. Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the effect of bedaquiline on drug-resistant tuberculosis. Between-study heterogeneity was examined by the I-squared test. Randomized controlled trials were assessed for quality using the Jadad scale, and cohort studies were assessed using the Newcastle–Ottawa scale. Results Eight studies, including 2 randomized controlled trials and 6 cohort studies involving a total of 21,836 subjects, were included. When compared with the control, bedaquiline treatment was associated with higher rates of culture conversion (risk ratio (RR):1.272 (1.165–1.389), P

BackgroundAnti-tuberculosis drug-induced liver injury (ATB-DILI) is one of the most common adverse reactions that brings great difficulties to the treatment of tuberculosis. Thus, early identification of individuals at risk for ATB-DILI is urgent. We conducted a prospective cohort study to analyze the urinary metabolic and microbial profiles of patients with ATB-DILI before drug administration. And machine learning method was used to perform prediction model for ATB-DILI based on metabolomics, microbiome and clinical data.MethodsA total of 74 new TB patients treated with standard first-line anti-TB treatment regimens were enrolled from West China Hospital of Sichuan University. Only patients with an updated RUCAM score of 6 or more were accepted in this study. Nontargeted metabolomics and microbiome analyses were performed on urine samples prior to anti-tuberculosis drug ingestion to screen the differential metabolites and microbes between the ATB-DILI group and the non-ATB-DILI group. Integrating electronic medical records, metabolomics, and microbiome data, four machine learning methods was used, including random forest algorithm, artificial neural network, support vector machine with the linear kernel and radial basis function kernel.ResultsOf all included patients, 69 patients completed follow-up, with 16 (23.19%) patients developing ATB-DILI after antituberculosis treatment. Finally, 14 ATB-DILI patients and 30 age- and sex-matched non-ATB-DILI patients were subjected to urinary metabolomic and microbiome analysis. A total of 28 major differential metabolites were screened out, involving bile secretion, nicotinate and nicotinamide metabolism, tryptophan metabolism, ABC transporters, etc. Negativicoccus and Actinotignum were upregulated in the ATB-DILI group. Multivariate analysis also showed significant metabolic and microbial differences between the non-ATB-DILI and severe ATB-DILI groups. Finally, the four models showed high accuracy in predicting ATB-DILI, with the area under the curve of more than 0.85 for the training set and 1 for the validation set.ConclusionThis study characterized the metabolic and microbial profile of ATB-DILI risk individuals before drug ingestion for the first time. Metabolomic and microbiome characteristics in patient urine before anti-tuberculosis drug ingestion may predict the risk of liver injury after ingesting anti-tuberculosis drugs. Machine learning algorithms provides a new way to predict the occurrence of ATB-DILI among tuberculosis patients.

Background: Anti-tuberculosis drug-induced liver injury (ATB-DILI) is an adverse reaction with a high incidence and the greatest impact on tuberculosis treatment. However, there is a lack of effective biomarkers for the early prediction of ATB-DILI. Herein, this study uses UPLC‒MS/MS to reveal the plasma metabolic profile and lipid profile of ATB-DILI patients before drug administration and screen new biomarkers for predicting ATB-DILI.Methods: A total of 60 TB patients were enrolled, and plasma was collected before antituberculosis drug administration. The untargeted metabolomics and lipidomics analyses were performed using UPLC‒MS/MS, and the high-resolution mass spectrometer Q Exactive was used for data acquisition in both positive and negative ion modes. The random forest package of R software was used for data screening and model building.Results: A total of 60 TB patients, including 30 ATB-DILI patients and 30 non-ATB-DILI subjects, were enrolled. There were no significant differences between the ATB-DILI and control groups in age, sex, smoking, drinking or body mass index (p > 0.05). Twenty-two differential metabolites were selected. According to KEGG pathway analysis, 9 significantly enriched metabolic pathways were found, and both drug metabolism-other enzymes and niacin and nicotinamide metabolic pathways were found in both positive and negative ion models. A total of 7 differential lipid molecules were identified between the two groups. Ferroptosis and biosynthesis of unsaturated fatty acids were involved in the occurrence of ATB-DILI. Random forest analysis showed that the model built with the top 30 important variables had an area under the ROC curve of 0.79 (0.65–0.93) for the training set and 0.79 (0.55–1.00) for the validation set.Conclusion: This study demonstrated that potential markers for the early prediction of ATB-DILI can be found through plasma metabolomics and lipidomics. The random forest model showed good clinical predictive value for ATB-DILI.

Abstract. Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.

Abstract The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Field experiments of nitrogen (N) treatment at five different application rates (0, 75, 150, 225, and 300 kg ha−1) were conducted under pot-seedling mechanical transplanting (PMT) in 2018 and 2019. Two high-quality and high-yielding hybrids of indica rice, Huiliangyou 898 and Y Liangyou 900, were used in this study. The N nutrition index (NNI) and accumulated N deficit (Nand), used to assess the N nutrition status in real-time, were calculated for the indica cultivars under PMT with a critical nitrogen concentration (Nc) dilution model based on shoot dry matter (DM) during the whole rice growth stage. The relationships between NNI and Nand with relative yield (RY) were determined, and accurate N application schemes were developed for hybrids indica rice under PMT. The results indicated that high application rate of N-fertilizer significantly increased the concentrations of shoot DM and N in aboveground organs during the observed stages in the two cultivars for two years (P