Search

Abstract The realm of self-healing materials integrates chemical and physical mechanisms that prevent wear and fracturing and extend the operational lifetime. Unlike the favorable rheology of amorphous soft materials that facilitates efficient contact between fragments, the efficiency of recovery of atomistically ordered materials is restricted by slower interfacial mass transport and the need for ideal physical alignment, which limits their real-world application. We report drastic enhancements in efficiency and recovery time in the self-healing of anilinium bromide, challenging these limitations. Crystals of this material recovered up to 49% within seconds and up to 95% after 100 min via ferroelastic detwinning. The spatial evolution of strain during cracking and healing was measured in real time using digital image correlation. Favorable alignment and strong ionic bonding across the interface of partially fractured crystals facilitate self-healing. This study elevates organic crystals close to the best-in-class self-healing polymers and sets an approach for durable crystal-based optoelectronics.

Abstract Background Several inflammatory indicators have been reported to have predictive value in many types of malignant cancer. This research was aimed to explore the ability of the monocyte-to-lymphocyte ratio (MLR) to predict prognosis in patients with intrahepatic cholangiocarcinoma (ICC) who subjected to curative hepatectomy. Methods This retrospective analysis included 196 patients with ICC who underwent curative hepatectomy between May 2018 and April 2023. The predictive abilities of the preoperative MLR in assessing overall survival (OS) and disease-free survival (DFS) in those patients were compared with other inflammation-based scores, including monocyte-to-white ratio, neutrophil-to-lymphocyte ratio, neutrophil-to-white ratio, platelet-to-lymphocyte ratio, platelet-to-white ratio, and systemic immune-inflammation index, as well as tumor markers, like carcinoembryonic antigen (CEA) and carbohydrate antigen 19 − 9 (CA19-9). Results The area under the time-dependent receiver operating characteristic curve indicated that the preoperative MLR had higher predictive efficiency in contrast with other inflammation-based scores and tumor markers in assessing OS and DFS. Stratifying patients according to the optimal cut-off value for the preoperative MLR, the data showed that both OS and DFS in the high MLR group were significantly worse than those in the low MLR group (p

Abstract Background Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients’ quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. Purpose Investigate the effects of tDCS on pain and physical function in patients with KOA. Methods Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. Results Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. Conclusions The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

Abstract Background Proliferative hepatocellular carcinomas (HCCs) is a class of aggressive tumors with poor prognosis. We aimed to construct a computed tomography (CT)-based radiomics nomogram to predict proliferative HCC, stratify clinical outcomes and explore the tumor microenvironment. Methods Patients with pathologically diagnosed HCC following a hepatectomy were retrospectively collected from two medical centers. A CT-based radiomics nomogram incorporating radiomics model and clinicoradiological features to predict proliferative HCC was constructed using the training cohort (n = 184), and validated using an internal test cohort (n = 80) and an external test cohort (n = 89). The predictive performance of the nomogram for clinical outcomes was evaluated for HCC patients who underwent surgery (n = 201) or received transarterial chemoembolization (TACE, n = 104). RNA sequencing data and histological tissue slides from The Cancer Imaging Archive database were used to perform transcriptomics and pathomics analysis. Results The areas under the receiver operating characteristic curve of the radiomics nomogram to predict proliferative HCC were 0.84, 0.87, and 0.85 in the training, internal test, and external test cohorts, respectively. The radiomics nomogram could stratify early recurrence-free survivals in the surgery outcome cohort (hazard ratio [HR] = 2.25; P

Abstract Individuals’ continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both social competition and hierarchy. However, the molecular regulatory mechanisms underlying the neural ensemble in the mPFC remains unclear. Here, we demonstrate that in excitatory neurons of prelimbic cortex (PL), lncRNA Sera remodels the utilization of Pkm Exon9 and Exon10, resulting in a decrease in the Pkm1/2 ratio in highly competitive mice. By employing a tet-on/off system, we disrupt or rebuild the normal Pkm1/2 ratio by controlling the expression of Pkm2 in PL excitatory neurons. We find that long-term Pkm2 modulation induces timely competition alteration and hysteretic rank change, through phosphorylating the Ser845 site of GluA1. Together, this study uncovers a crucial role of lncRNA Sera/Pkm2 pathway in the transition of social competition to rank by remodeling neural ensemble in mPFC.

Abstract Although circular RNAs (circRNA) have been demonstrated to modulate tumor initiation and progression, their roles in the proliferation of hepatocellular carcinoma (HCC) are still poorly understood. Based on the analysis of GEO data (GSE12174), hsa-circRNA-0015004 (circ-0015004) was screened and validated in 80 sets of HCC specimens. Subcellular fractionation analysis was designed to determine the cellular location of circ-0015004. Colony formation and cell counting kit-8 were performed to investigate the role of circ-0015004 in HCC. Dual-luciferase reporter gene assays, RNA immunoprecipitation and chromatin immunoprecipitation were employed to verify the interaction among circ-0015004, miR-330-3p and regulator of chromatin condensation 2 (RCC2). The expression level of circ-0015004 was significantly upregulated in HCC cell lines and HCC tissues. HCC patients with higher circ-0015004 levels displayed shorter overall survival, and higher tumor size and TNM stage. Moreover, knockdown of circ-0015004 significantly reduced HCC cell proliferation in vitro and inhibited the growth of HCC in nude mice. Mechanistic studies revealed that circ-0015004 could upregulate the expression of RCC2 by sponging miR-330-3p, thereby promoting HCC cell proliferation. Furthermore, we identified that Ying Yang 1 (YY1) could function as an important regulator of circ-0015004 transcription. This study systematically demonstrated the novel regulatory signaling of circ-0015004/miR-330-3p/RCC2 axis in promoting HCC progression, providing insight into HCC diagnosis and treatment from bench to clinic.

Abstract Studying the penetration characteristics of blast‐induced cracks during double water jet slotted boreholes blasting is theoretically and practically significant since it acts both by the “superposition effect” of explosion‐induced stress waves and the “guiding effect” of water jet slots. A combination of experimental testing and numerical simulation was adopted to investigate the transmission law of explosion‐induced stress waves and the propagation law of blast‐induced cracks first. Then the penetration characteristics of blast‐induced cracks was analyzed according to rock blasting theory and rock fracture mechanics theory. The results indicate that the rock between the two boreholes is mainly subjected to a tensile failure mode due to the combined effect of the “superposition effect” of explosion‐induced stress wave and the “guiding effect” of water jet slot during double water jet slotted boreholes blasting. The hole spacing significantly affects the penetration mode of blast‐induced cracks during double water jet slotted boreholes blasting, and unless it reaches a certain value, a single flat through‐crack will form between two slotted boreholes. In addition, when the blast‐induced cracks successfully penetrate each other, the hole spacing of double water jet slotted boreholes increases by 33.3% compared with that of double circular boreholes under the same conditions. The research results can provide guidance for the application of directional controlled blasting technology with water jet assistance.

Abstract Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR‐136‐5p or Smurf1 expression were transfected into BMSCs. The effects of miR‐136‐5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR‐136‐5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR‐136‐5p/BMSCs/β‐TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro‐CT and HE staining. Elevating miR‐136‐5p‐3p or suppressing Smurf1 could stimulate OD of BMSCs. miR‐136‐5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR‐136‐5p on the OD of BMSCs. miR‐136‐5p/BMSCs/β‐TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1‐targeting miR‐136‐5p‐modified BMSCs combined with 3D‐printed β‐TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

Microplastics have emerged as a significant global concern, particularly in marine ecosystems. While extensive research has focused on the toxicological effects of microplastics on marine animals and/or their associated microorganisms as two separate entities, the holistic perspective of the adaptability and fitness of a marine animal metaorganism—comprising the animal host and its microbiome—remains largely unexplored. In this study, mussel metaorganisms subjected chronic PS-MPs exposure experienced acute mortality but rapidly adapted. We investigated the response of innate immunity, digestive enzymes and their associated microbiomes to chronic PS-MPs exposure. We found that PS-MPs directly and indirectly interacted with the host and microbe within the exposure system. The adaptation was a joint effort between the physiological adjustments of mussel host and genetic adaptation of its microbiome. The mussel hosts exhibited increased antioxidant activity, denser gill filaments and increased immune cells, enhancing their innate immunity. Concurrently, the gill microbiome and the digestive gland microbiome respective selectively enriched for plastic-degrading bacteria and particulate organic matter-utilizing bacteria, facilitating the microbiome’s adaptation. The microbial adaptation to chronic PS-MPs exposure altered the ecological roles of mussel microbiome, as evidenced by alterations in microbial interactions and nutrient cycling functions. These findings provided new insights into the ecotoxicological impact of microplastics on marine organisms from a metaorganism perspective.

The human body is a complex, integral whole, and disruptions in one organ can lead to dysfunctions in other parts of the organ network. The facial nerve, as the seventh cranial nerve, arises from the brainstem, controls facial expression muscles and plays a crucial role in brain-body communication. This vulnerable nerve can be damaged by trauma, inflammation, tumors, and congenital diseases, often impairing facial expression. Stem cells have gained significant attention for repairing peripheral nerve injuries due to their multidirectional differentiation potential. Additionally, various biomaterials have been used in tissue engineering for regeneration and repair. However, the therapeutic potential of stem cells and biomaterials in treating facial nerve injuries requires further exploration. In this review, we summarize the roles of stem cells and biomaterials in the regeneration and repair of damaged facial nerves, providing a theoretical basis for the recovery and reconstruction of body-brain crosstalk between the brain and facial expression muscles.

The influence of the grain sizes ranging from 23.4 to 69.2 μm on mechanical properties of Cu-3wt.%Ag-0.5 wt%Zr thin sheets was investigated by conducting uniaxial tensile experiments at room temperature (RT 298 K) and cryogenic temperature (CT 77 K). At RT, the strength and ductility of the sheet decreased as the grain size increased, and the size effect on flow stress was observed when the ratio of thickness to grain size (t/d) was less than 4.5. At CT, the sheet exhibited excellent strength and ducility, accompanied by a reduction in the size effect on flow stress. GND distribution maps showed that the average GND density of grains in the sample surface (surface grains) was lower than that of grains in the core of the sample (core grains). As the distance from the grain boundary increased, the GND density decreased. A constitutive model was developed for Cu-3wt.%Ag-0.5 wt%Zr thin sheets based on the dislocation accumulation and recovery process, which was able to predict the effects of grain size and deformation temperature on the flow stress and GND evolution in Cu-3wt.%Ag-0.5 wt%Zr thin sheets. This constitutive model indicated that CT not only inhibited the GND recovery process but likewise promoted the GND accumulation process. The established constitutive model revealed that the ratio of SSD density to GND density increased with increasing strain. The total dislocation density and GND density of samples deformed at CT was higher than those of samples deformed at RT.

Abstract Fracture is an important factor that affects the oil and gas productivity of carbonate reservoirs. Much researches have been done on the origin of high-angle fractures in carbonate reservoirs, but few efforts have been made on the genetic mechanical mechanism of low-angle fractures. Based on the seismic data, core data, conventional logging data and rock mechanics experimental data, combined with three-dimensional in situ stress field simulation methods, the features, formation geological conditions and genetic mechanical mechanism of low-angle fractures (LAFs) were analyzed by applying Coulomb–Moore criterion, Griffith criterion and non-coordination criterion. The proportion of the number of shear fractures is as high as 90.2%, while that of tensile fractures is only 9.8% in the study area. Shear fractures are mainly unfilled fractures, and tensile fractures are mainly partially filled fractures. The LAFs were formed in the second tectonic movement, in which the knee-fold structure with high in the west and low in the east developed in the study area. The buried depth of most parts of the KT-I formation is 800 m when the study area develops the knee-fold structure, with a maximum depth of 1800 m and a minimum buried depth of 70 m, and the dip angle of the steepest part of the stratum is about 20°. A large number of LAFs were formed in the study area under the joint influence of tectonics and abnormally high pressure of water, including near-horizontal LAFs in the non-weak fabrics section (type I low-angle shear fractures), the LAFs having a certain angle with bedding in the non-weak fabrics section (type II low-angle shear fractures) and near-horizontal LAFs in the weak fabrics section (type III low-angle shear fractures). The formation of type I and type II low-angle shear fractures follows the Coulomb–Moore criterion. Type I low-angle shear fractures are formed in strata with a certain dip angle, while type II low-angle shear fractures are formed in near-horizontal strata. Type III low-angle shear fractures are formed under the comprehensive influence of pre-existing weak fabrics and strong horizontal extrusion, which follows the non-coordination criterion. Low-angle tensile fractures are mainly caused by abnormally high pressure and reverse faults in the study area, following Griffith’s criterion. The research in this paper not only reveals the formation mechanical mechanism of LAFs in pre-salt carbonate reservoirs but also provides guidance for the prediction of LAFs and solving the problem of water channeling caused by LAFs in oil fields.

Energy storage and conservation are receiving increased attention due to rising global energy demands. Therefore, the development of energy storage materials is crucial. Thermal energy storage (TES) systems based on phase change materials (PCMs) have increased in prominence over the past two decades, not only because of their outstanding heat storage capacities but also their superior thermal energy regulation capability. However, issues such as leakage and low thermal conductivity limit their applicability in a variety of settings. Carbon-based materials such as graphene and its derivatives can be utilized to surmount these obstacles. This study examines the recent advancements in graphene-based phase change composites (PCCs), where graphene-based nanostructures such as graphene, graphene oxide (GO), functionalized graphene/GO, and graphene aerogel (GA) are incorporated into PCMs to substantially enhance their shape stability and thermal conductivity that could be translated to better storage capacity, durability, and temperature response, thus boosting their attractiveness for TES systems. In addition, the applications of these graphene-based PCCs in various TES disciplines, such as energy conservation in buildings, solar utilization, and battery thermal management, are discussed and summarized.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. Results Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. Conclusions Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis. Graphical abstract

Abstract Background Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. Methods Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1 −/− ) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. Results In vivo, Itln-1 −/− mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. Conclusion The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Abstract Objective To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. Methods In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. Results The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. Conclusion Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one’s diet and taking ezetimibe can well control blood lipids.

Aims Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis.Methods This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein.Results In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was −6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1.Conclusion CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

ABSTRACTSome benign and malignant breast tumours are similar in pathological morphology, which are difficult to be distinguished in clinical diagnosis. In this study, we intended to explore novel biomarkers for differential diagnosis of benign and malignant breast tumours. Methylation EPIC 850K beadchip and RNA-sequencing were used to analyse 29 tissue samples from patients with early-stage breast cancer (BC) and benign breast tumours for differently methylated and expressed genes. The altered methylation of IL21R was semi-quantitatively validated in an independent study with 566 tissue samples (279 BC vs. 287 benign breast tumours) using mass spectrometry. Binary logistic regression analysis was performed to evaluate the association between IL21R methylation and BC. BC-associated IL21R hypomethylation and overexpression were identified in the discovery round. In the validation round, BC patients presented significant IL21R hypomethylation compared to women with benign breast tumours (ORs ≥1.29 per-10% methylation, p-values ≤ 5.69E–14), and this hypomethylation was even enhanced in BC patients with ER-negative and PR-negative tumours as well as with triple-negative tumours. The methylation of IL21R showed efficient discriminatory power to distinguish benign breast tumours from BC (area under curve (AUC) = 0.88), and especially from ER-negative BC (AUC = 0.95), PR-negative BC (AUC = 0.93) and triple-negative BC (AUC = 0.96). We disclosed significant IL21R hypomethylation in patients with BC compared to women with benign breast tumours, and revealed the somatic change of DNA methylation could be a potential biomarker for molecular pathology of BC.

Purpose: To assess the clinical benefits of surface-guided radiation therapy (SGRT) in terms of setup error, positioning time, and clinical target volume-to-planning target volume (CTV-PTV) margin in extremity soft tissue sarcoma (STS). Methods and Materials: Fifty consecutive patients treated with radiation therapy were selected retrospectively. Treatment setup was performed with either laser-based imaging only (control group), or with laser-based and daily optical surface-based imaging (SGRT group). Pretreatment cone beam computed tomography images were acquired daily for the first 3 to 5 fractions and weekly thereafter, with the frequency adjusted as necessary. Translational and rotational errors were collected. CTV-PTV margin was calculated using the formula, 2.5Σ + 0.7σ. Results: Each group consisted of 10 and 15 upper and lower limb STSs, respectively. For patients with upper limb sarcomas, the translation errors were 1.64 ± 1.34 mm, 1.10 ± 1.50 mm, and 1.24 ± 1.45 mm in the SGRT group, and 1.48 ± 3.16 mm, 2.84 ± 2.85 mm, and 3.14 ± 3.29 mm in control group in the left-right, supero-inferior, and antero-posterior directions, respectively. Correspondingly, for patients with lower limb sarcomas, the translation errors were 1.21 ± 1.65 mm, 1.39 ± 1.71 mm, and 1.48 ± 2.10 mm in the SGRT group, and 1.81 ± 2.60 mm, 2.93 ± 3.28 mm, and 3.53 ± 3.75 mm in control group, respectively. The calculated CTV-PTV margins of the SGRT group and control group were 5.0, 3.8, 4.1 versus 5.9, 9.1, 10.1 mm for upper limb sarcomas; and 4.2, 4.7, 5.2 mm versus 6.3, 9.6, and 11.4 mm for lower limb sarcomas in the left-right, supero-inferior, and antero-posterior directions, respectively. Conclusions: Daily optical surface guidance can effectively improve the setup accuracy of extremity STS patients, and safely reduce the required CTV-PTV margins.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

BackgroundAmiodarone is a class III antiarrhythmic drug that is commonly used in the clinic to treat ventricular arrhythmias and atrial fibrillation. We present a case report of the adverse effects of amiodarone and review its characteristics.Case reportA 73-year-old Asian female with a history of paroxysmal atrial fibrillation managed with amiodarone, well-controlled hypertension, and no substance abuse presented with gastrointestinal distress and dizziness, without chest pain or palpitations. Despite normal annual check-ups, she developed abnormal liver and thyroid function tests, and imaging revealed lung and liver changes suggestive of amiodarone toxicity. Discontinuation of amiodarone for sotalol led to symptom improvement and normalization of thyroid and liver functions, with imaging indicating recovery from interstitial fibrosis and reduced liver density.DiscussionAmiodarone, a widely used for treating ventricular and atrial arrhythmias, and with significant benefits in improving patient survival in cases of ventricular fibrillation. However, its long-term use is associated with serious adverse effects, including thyroid dysfunction, liver injury, and pulmonary toxicity, necessitating careful monitoring and management. Despite its efficacy, the need for research on early detection and management of amiodarone's side effects is crucial, highlighting the importance of regular monitoring and possibly adjusting therapy to mitigate these risks.

Abstract Glycans are complex biomolecules that encode rich information and regulate various biological processes, such as fertilization, host‐pathogen binding, and immune recognition, through interactions with glycan‐binding proteins. A key driving force for glycan‐protein recognition is the interaction between the π electron density of aromatic amino acid side chains and polarized C─H groups of the pyranose (termed the CH–π interaction). However, the relatively weak binding affinity between glycans and proteins has hindered the application of glycan detection and imaging. Here, computational modeling and molecular dynamics simulations are employed to design a chemical strategy that enhances the CH–π interaction between glycans and proteins by genetically incorporating electron‐rich tryptophan derivatives into a lectin PhoSL, which specifically recognizes core fucosylated N‐linked glycans. This significantly enhances the binding affinity of PhoSL with the core fucose ligand and enables sensitive detection and imaging of core fucosylated glycans in vitro and in xenograft tumors in mice. Further, the study showed that this strategy is applicable to improve the binding affinity of GafD lectin for N‐acetylglucosamine‐containing glycans. The approach thus provides a general and effective way to manipulate glycan‐protein recognition for glycoscience applications.

Abstract Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride‐based alloys are still the best for near‐room‐temperature applications. In this work, a ≈38% enhancement of the average ZT (300−473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2−yTe3‐based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6‐based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high‐density dislocations in the same region can effectively scatter the phonons, decoupling the electron‐phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single‐leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate‐matrix interface microstructure in improving the performance of materials for relatively low‐temperature applications.

Treatment of lower limb ischemia in patients with diabetes is challenging because of the location of the ulcers and the complexity of their pathogenesis. Carbon dioxide fractional laser (CO 2 FL) therapy in conjunction with tibial periosteum distraction could become a substitute for conventional methods. We herein describe a patient diagnosed with ischemic diabetic foot with a complex ulcer in the upper third of the tibia. Laser irradiation (Deep FX mode with 30 mJ of energy and 10% density) was applied to the entire region of skin below the knee after surface anesthesia, and this treatment was performed twice a week until the ulcer healed. Computed tomography angiography showed successful establishment of a blood supply to the back of the right foot after treatment. Skin grafting was successfully performed, with only a few wounds remaining on the foot 8 months after treatment. The pain score was significantly decreased at the last follow-up. No complications occurred. This case report provides guidance for the performance of CO 2 FL, a fast, easy, accurate treatment in patients with diabetes. CO 2 FL can target lower limb arterial occlusive disease accompanied by refractory ulcers, addressing the underlying vascular occlusion and dysfunction as well as promoting microcirculation and wound healing.

Abstract In this work, 2D ferromagnetic M3GeTe2 (MGT, M = Ni/Fe) nanosheets with rich atomic Te vacancies (2D‐MGTv) are demonstrated as efficient OER electrocatalyst via a general mechanical exfoliation strategy. X‐ray absorption spectra (XAS) and scanning transmission electron microscope (STEM) results validate the dominant presence of metal‐O moieties and rich Te vacancies, respectively. The formed Te vacancies are active for the adsorption of OH* and O* species while the metal‐O moieties promote the O* and OOH* adsorption, contributing synergistically to the faster oxygen evolution kinetics. Consequently, 2D‐Ni3GeTe2v exhibits superior OER activity with only 370 mV overpotential to reach the current density of 100 mA cm−2 and turnover frequency (TOF) value of 101.6 s−1 at the overpotential of 200 mV in alkaline media. Furthermore, a 2D‐Ni3GeTe2v‐based anion‐exchange membrane (AEM) water electrolysis cell (1 cm2) delivers a current density of 1.02 and 1.32 A cm−2 at the voltage of 3 V feeding with 0.1 and 1 m KOH solution, respectively. The demonstrated metal‐O coordination with abundant atomic vacancies for ferromagnetic M3GeTe2 and the easily extended preparation strategy would enlighten the rational design and fabrication of other ferromagnetic materials for wider electrocatalytic applications.

This research initially presents an internal structure optimization technique through numerical investigation with the intention of addressing the issues of unstable and poorly adjustable combustion flame of porous media methanol furnace. The entire premixed combustion technology and the flue gas waste heat evaporation technology are then combined in a combustion technology that is based on this stove structure. As a result, this resolves substantially the issues with methanol stove tempering, misfire, and uneven temperature. The fully premixed methanol cooker was eventually created and put into wide production. According to the findings, the flow rate was between 0.25 and 0.7 m/s before the cooker structural improvement and around 0.45 m/s after. More crucially, by eliminating the low temperature zone of approximately 300 °C and raising the temperature to about 500 °C, the temperature field at the cooker's exit porous medium was much improved. Additionally, the methanol cooker in the typical diffusion combustion mode was outperformed by the full premixed combustion technology and flue gas waste heat evaporation technology in this trial in terms of complete fuel combustion with no pollutant emissions. The study's findings indicate that the cooker's overall thermal efficiency is 68.2%, which has clear financial benefits.

Abstract Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation. Mechanistically, TSC1 in macrophages promoted AKT and MST1 phosphorylation, and protected NRF2 from Keap1-mediated ubiquitination. Furthermore, overexpression AKT or MST1 in TSC1-knockout macrophages upregulated NRF2 expression, downregulated TLR4/NF-κB, resulting in reduced inflammatory factors, ROS and inflammatory cytokine-mediated hepatocyte apoptosis. Strikingly, TSC1 induction in NRF2-deficient macrophages failed to reverse the TLR4/NF-κB activity and production of pro-inflammatory factors. Conclusions: Macrophage TSC1 promoted the activation of the AKT/MST1 signaling pathway, increased NRF2 levels via reducing Keap1-mediated ubiquitination, and modulated oxidative stress-driven inflammatory responses in liver I/R injury. Our findings underscore the critical role of macrophage TSC1 as a novel regulator of innate immunity and imply the therapeutic potential for the treatment of sterile liver inflammation in transplant recipients. Schematic illustration of macrophage TSC1-mediated AKT/MST1/NRF2 signaling pathway in I/R-triggered liver inflammation. Macrophage TSC1 can be activated in I/R-stressed livers. TSC1 activation promotes phosphorylation of AKT and MST1, which in turn increases NRF2 expression and inhibits ROS production and TLR4/NF-κB activation, resulting in reduced hepatocellular apoptosis in I/R-triggered liver injury.

This paper presents a comparative analysis of electromagnetic performance of radial flux dual-rotor surface-mounted permanent magnet (SPM) machines with fractional slot non-overlapping windings, with reference to external- and internal-rotor SPM machines. All machines are optimised by genetic algorithm using finite element analysis under various design optimisation scenarios, together with the equivalent magnetic circuit analysis. In addition, the influence of air gap length, PM volume, machine inner bore radius, and pole number is investigated. The results have revealed that the dual rotor SPM machine has lower torque but higher overload capability than the single rotor SPM machines, as confirmed by experimental results.

This paper presents a novel system-level design approach for optimizing electric vehicle (EV) traction motors. The technique tackles limitations of traditional finite element analysis software and allows for optimizing the entire electrical machine, power electronics, and control strategy design across a complete drive-cycle instead of a single operating point. Using the Worldwide Harmonized Light Vehicles Test Procedure (WLTP) as a benchmark, the proposed co-optimization technique is applied to an Electrically Excited Synchronous Machine (EESM) to maximize drive-cycle efficiency. In addition, Dynamic Motor Drive (DMD) strategy is applied to address the mismatch issue between typical EV operation and electrical machine efficiency zones to further reduce the power loss. Analytical results reveal that the optimized EESM system, when using DMD, exhibits superior torque, power, and drive-cycle efficiency compared to a commercial benchmark Interior Permanent Magnet (IPM) motor.

This paper systematically investigates the effect of multi-tooth numbers on electromagnetic performances of conventional and consequent-pole (CP) vernier permanent magnet (PM) synchronous machines (VPMSMs), including average torque, overload capability, PM utilization, loss, efficiency, and power factor, etc. In particular, the influence of multi-tooth numbers on the unipolar end leakage flux of CP VPMSMs is investigated for the first time. It confirms that CP rotor and multi-tooth stator structures exhibit better field modulation effects compared with conventional north-south pole and non-multi-tooth stator structures. It reveals that there exists an optimal multi-tooth number for torque output capability and PM utilization, as well as unipolar end leakage flux. In particular, it shows that the multi-tooth stator structure helps save PM volume significantly for CP VPMSMs and suppress unipolar end leakage flux. The PM utilization rate of CP VPMSM with 5 multi-teeth is more than 50% higher than that with single-tooth structure while the unipolar end leakage flux is reduced by around 60%. However, the overload capability and power factor will be sacrificed. Finally, the prototypes with 2 and 3 multi-teeth numbers are manufactured and tested to verify the FEA analyses.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. Methods This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum β-D-glucan levels was also evaluated for PCP diagnosis. Results A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum β-D-glucan levels (AUC = 0.752; 95% CI: 0.597–0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum β-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). Conclusions Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum β-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. Trial registration ClinicalTrials.gov (NCT05701631).

This paper presents a novel method for addressing the challenge of dq-transformation in fractional-slot machines with star-delta connected concentrated windings. These machines have no neutral point, preventing direct measurement of mutual inductance between phases. This complicates the calculation of d- and q-axis inductances, which are crucial for modern control techniques such as field-oriented and sensorless control. The proposed method derives d- and q-axis inductances as functions of individual star and delta coil inductances, which can easily be measured. Moreover, it demonstrates that the d- and q-axis inductances can be calculated using measurements from just two adjacent coils. The method begins with constructing a decomposed coil-by-coil inductance matrix, separating each phase winding into individual star and delta coil inductances. This matrix is then transformed into the dq-frame using a three-step process: firstly, summing individual flux linkages to derive line flux linkage based on circuit configuration; secondly, decomposing 3-phase abc supply currents into individual currents within the star and delta coils to address phase shift and amplitude differences; and finally, transforming line flux linkage into the dq-frame using a modified power-invariant Park transformation. The proposed method is validated by simulations and experiments on both surface mounted and interior permanent magnet machines.

Tidal flats are an important part of coastal wetland systems and play an irreplaceable role in maintaining the health of global coastal ecosystems, resisting natural coastal disasters, and sequestering blue carbon. For the coastal zone around Beibu Gulf, where tidal flats are densely distributed, the spatiotemporal characteristics of tidal flats evolution and its key driving factors remain unclear. This article took the Beibu Gulf as the study area, and constructed an integrated tidal flats extraction algorithm of “maximum spectral index composite (MSIC) + Otsu algorithm (OTSU) + DEM correction” based on the cloud computing platform of Google Earth Engine to realize a large-scope and high-accuracy automatic extraction of tidal flats. The results discovered that 1) the tidal flats extraction method proposed in this study has high accuracy, with the overall accuracy of the confusion matrix reaching 93.9%, and the Kappa coefficient reaching 0.82. The user accuracy and mapping accuracy of the tidal flats are both greater than 85%. 2) In 35 years, the total tidal flats area of the Beibu Gulf has decreased by 683.9 km2, a reduction of 29%, and the average annual rate of change was −19.5 km2/a. 3) The fragmentation state of the tidal flats in Beibu Gulf intensified with time, and the natural driving forces of the tidal flats were mainly the rise in sea level, decrease in the amount of sediment in the river entering the sea, and expansion of mangrove trees. Human-driven forces were mainly coastal economic development and offshore aquaculture.

Uncertainty is a key issue in thermal analysis and management for permanent magnet (PM) synchronous machines (PMSMs) and always occurs in both conduction and convection heat transfers. However, this issue has not been evaluated thoroughly. Therefore, this paper presents a comprehensive sensitivity analysis with uncertainty quantification, and the influences of more than 20 uncertain factors on temperature rises of winding and PM are evaluated. The investigated uncertainties include the convection coefficients under different cooling methods, the main machine losses, the interface gaps, and the materials’ thermal conductivities, where a 3-kW outer rotor PMSM is taken as an example for illustration. Furthermore, the most critical uncertain factors are determined based on a well-calibrated finite element analysis (FEA) model. Finally, the employed FEA model is validated experimentally under different cooling conditions.

A new species of xenodermid snake, Achalinus nanshanensis H. Li, L.-Q. Zhu, Z.-Q. Zhang & X.-Y. Mo, sp. nov., is described based on three specimens collected from Nanshan National Park and Tongdao County of southwest Hunan Province. This new species is genetically distinct amongst its congeners with the mitochondrial COI uncorrected p-distance ranging from 4.4% (in A. yangdatongi) to 17.7% (in A. meiguensis). In addition, this new species can be distinguished from its congeners by a combination of the following morphological characters: (1) dorsal scales with 23 or 25 rows throughout and strongly keeled; (2) tail relatively longer so that TaL/ToL = 0.215–0.248; (3) length of suture between internasals significantly longer than that between prefrontals, LSBI/LSBP = 1.66–1.84; (4) single loreal scale present; (5) SPL 6 in number, with the fourth and fifth contacting eye; (6) IFL 6 in number, with the first three touching the first pair of chin shields; (7) TMP is 2-2-4/2-2(3)-4, with the anterior pair elongated and in contact with the eye; (8) ventrals 2 + 147–158; (9) subcaudals 64–77, unpaired; (10) dorsal body brownish black, with a bright yellow neck collar extending to the head and abdomen in the occipital region. The recognition of the new species increases the number of described Achalinus species to 28, of which 21 are found in China.

The rapid development of deep learning has made a great progress in salient object detection task. Fully supervised methods need a large number of pixel-level annotations. To avoid laborious and consuming annotation, weakly supervised methods consider low-cost annotations such as category, bounding-box, scribble, etc. Due to simple annotation and existing large-scale classification datasets, the category annotation based methods have received more attention while still suffering from inaccurate detection. In this work, we proposed one weakly supervised method with category annotation. First, we proposed one coarse object location network (COLN) to roughly locate the object of an image with category annotation. Second, we refined the coarse object location to generate pixel-level pseudo-labels and proposed one quality check strategy to select high quality pseudo labels. To this end, we studied COLN twice followed by refinement to obtain a pseudo-labels pair and calculated the consistency of pseudo-label pairs to select high quality labels. Third, we proposed one multi-decoder neural network (MDN) for saliency detection supervised by pseudo-label pairs. The loss of each decoder and between decoders are both considered. Last but not least, we proposed one pseudo-labels update strategy to iteratively optimize pseudo-labels and saliency detection models. Performance evaluation on four public datasets shows that our method outperforms other image category annotation based work.

Abstract Drones play an important role in modern cities, they bring convenience but also bring corresponding risks. Falling drones can cause casualties or damage to urban facilities and serious property damage, which increases the third-party risk problem. An effective way to reduce these third-party risks is to avoid high-risk areas in path planning, but most current path planning methods are optimized to minimize flight distance, and third-party risk costs are rarely considered. In this paper, a comprehensive risk-cost UAV path planning method is proposed, which evaluates urban risk by establishing a third-party risk model that incorporates obstacle risk, death risk, and property loss risk. This paper proposes a Min-cost A* algorithm based on city risk assessment, and smooths the generated low-risk path through the improved Floyd algorithm. The results show that the path planning method can effectively reduce the risk in the flight path, improve the reliability of the UAV flight path in the urban environment, and solve the problem of planning the third-party risk path of the UAV.

Abstract The serine/threonine kinase, PINK1, and the E3 ubiquitin ligase, Parkin, are known to facilitate LC3-dependent autophagosomal encasement and lysosomal clearance of dysfunctional mitochondria, and defects in this process contribute to a variety of cardiometabolic and neurological diseases. Although recent evidence indicates that dynamic actin remodeling plays an important role in PINK1/Parkin-mediated mitochondrial autophagy (mitophagy), the underlying signaling mechanisms remain unknown. Here, we identify the RhoGAP GRAF1 (Arhgap26) as a PINK1 substrate that regulates mitophagy. GRAF1 promotes the release of damaged mitochondria from F-actin anchors, regulates mitochondrial-associated Arp2/3-mediated actin remodeling and facilitates Parkin-LC3 interactions to enhance mitochondria capture by autophagosomes. Graf1 phosphorylation on PINK1-dependent sites is dysregulated in human heart failure, and cardiomyocyte-restricted Graf1 depletion in mice blunts mitochondrial clearance and attenuates compensatory metabolic adaptations to stress. Overall, we identify GRAF1 as an enzyme that coordinates cytoskeletal and metabolic remodeling to promote cardioprotection.

Density–density correlation analysis is a convenient diagnostic tool to reveal the hidden order in the strongly correlated phases of ultracold atoms. We report on a study of the density–density correlations of ultracold bosonic atoms which were initially prepared in a Mott insulator (MI) state in one-dimensional optical lattices. For the atomic gases released from the deep optical lattice, we extracted the normalized density–density correlation function from the atomic density distributions of freely expanded atomic clouds. Periodic bunching peaks were observed in the density–density correlation spectra, as in the case of higher-dimensional lattices. Treating the bosonic gas within each lattice well as a subcondensate without quantum tunneling, we simulated the post-expansion density distribution along the direction of the 1D lattice, and the calculated density–density correlation spectra agreed with our experimental observations.

Variations in the tumor genome can result in allelic changes compared to the reference profile of its homogenous body source on genetic markers. This brings a challenge to source identification of tumor samples, such as clinically collected pathological paraffin-embedded tissue and sections. In this study, a probabilistic model was developed for calculating likelihood ratio (LR) to tackle this issue, which utilizes short tandem repeat (STR) genotyping data. The core of the model is to consider tumor tissue as a mixture of normal and tumor cells and introduce the incidence of STR variants (φ) and the percentage of normal cells (Mxn) as a priori parameters when performing calculations. The relationship between LR values and φ or Mxn was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had Log10(LR) values greater than 1014. In the non-contributor test, 99.9% of the quartiles had Log10(LR) values less than 0. When the defense’s hypothesis took into account the possibility that the tumor samples came from the patient’s relatives, LR greater than 0 was still obtained. Furthermore, this study revealed that LR values increased with decreasing φ and increasing Mxn. Finally, LR interval value was provided for each tumor sample by considering the confidence interval of Mxn. The probabilistic model proposed in this paper could deal with the possibility of tumor allele variability and offers an evaluation of the strength of evidence for determining tumor origin in clinical practice and forensic identification.

In the face of escalating global climate challenges, effective carbon dioxide (CO₂) capture techniques remain at the forefront of mitigating anthropogenic greenhouse gas emissions. This comprehensive review elucidates the latest advancements in CO₂ capture, emphasizing two predominant methodologies: absorption and adsorption. We delve into the mechanisms underlying each process, highlighting the novel materials and technologies that have emerged over recent years. For absorption, the focus is placed on the material design strategy, and identifying new materials in the class of amines, ionic liquids (ILs) and nanofluids for enhanced CO2 capture capacities and reduced energy requirements. In the realm of adsorption, the synthesis of innovative adsorbents, such as metal organic framework (MOF), organic polymers, inorganic adsorbents, silicon-based adsorbents, and biochar and byproducts from biomass with superior selectivity and stability, is explored. Additionally, the review addresses the challenges associated with each method, offering insights into potential avenues for further research. By providing a holistic overview of the current landscape of CO₂ capture, this article serves as a pivotal resource for researchers and industry professionals aiming to advance sustainable solutions to combat climate change.

With the development of product miniaturization in aerospace and other fields, nickel-based superalloy thin sheets with excellent comprehensive properties have become crucial materials for micro-components in these fields. Due to the complexity of the initial microstructure and strengthening mechanism, there is a lack of in-depth research on the mesoscale formability of nickel-based superalloys under the coupled effects of multiple factors such as feature size (i.e., the ratio of specimen thickness to grain size, t/d), particle size and volume content of the precipitated phase. In this paper, a test platform was constructed for the application of high-precision strain measurements to the analysis of the mesoscale forming limit, and the mechanisms for the influences of feature size and precipitation on the mesoscale forming limit of a nickel-based superalloy were studied. The results showed that feature size influenced the forming limit of the nickel-based superalloy thin sheet at the mesoscopic scale, and the formability decreased with decreasing t/d and increasing γ′′/γ′ particle size and volume content. Based on surface layer theory and ductile fracture theory, the influences of t/d and γ′′/γ′ phases on the forming limit of nickel-based superalloy thin sheets at the mesoscopic scale were revealed. The coupled effects of surface roughening caused by free surface grains and hindered dislocation movement induced by precipitated phases resulted in strain localization and reduced the forming properties of nickel-based superalloy thin sheets at the mesoscopic scale.

Nickel-based superalloys have become essential materials due to their excellent comprehensive properties as the miniaturization of products in the aerospace and energy fields develops. The complex microstructure and various strengthening mechanisms of nickel-based superalloys make the plastic deformation behavior extremely complicated at the mesoscopic scale. In this paper, compression experiments of nickel-based superalloy samples with different feature sizes (i.e. the sample diameter to grain size ratio, D/d) and different aging times at the mesoscopic scale were carried out. The coupling effect of feature size and δ phase on the compressive deformation behavior was studied. The results show that the δ phase plays a role in precipitation strengthening during compressive deformation at the mesoscopic scale. When D/d is in the range of 9.7–10.9, the flow stress decreases significantly with the increase of grain size, and a “smaller is weaker” size effect appears. When D/d is less than 9.7, the flow stress increases with the grain size, and a “smaller is stronger” size effect appears. Considering grain boundary strengthening, solid solution strengthening, and precipitation strengthening, a size effect model of flow stress was established. The calculated values were in good agreement with the experimental values. The inhomogeneity of the end surface and side surface increases with the decrease of feature size and the decrease of aging time. The presence of the δ phase reduces the inhomogeneous deformation of nickel-based superalloys during compressive deformation at the mesoscopic scale.

This paper investigates the use of fractional-slot concentrated windings (FSCWs) in large-scale (MW level) offshore wind generators. It focuses specifically on a power rating of 3 MW and uses an existing direct-drive synchronous PM machine (DD-SPM) with 480s/160p and dual three-phase integer-slot winding (ISW) as a baseline. A multiple of the common 12s/10p FSCW machine is used that matches the electrical frequency of the ISW machine, yielding a 192s/160p dual three-phase machine. The hybrid star–delta connection has grown increasingly popular owing to its unique harmonic cancellation properties, which can help reduce rotor and PM eddy current losses in FSCW machines. In this paper, two dual three-phase star–delta-wound machines are scaled to 3 MW and included in the investigation. Specifically, a 384s/160p dual three-phase and dual star–delta winding machine, which is a multiplication of the 24s/10p machine, and a 192s/176p dual three-phase and dual star–delta winding machine, which is a multiplication of the 24s/22p machine, are used. These machines are investigated using finite element analysis (FEA) and compared on the basis of their air-gap flux density harmonics, open-circuit electro-motive force (EMF), torque performance, and losses and power. It is found that the proposed 384s/160p dual star–delta winding machine has the best electromagnetic performance of all, with a stator power that is 1.2% greater than that of the baseline ISW machine. However, this machine has a coil pitch of 2 and so loses the manufacturing and fault-tolerant advantage of having concentrated windings. If concentrated windings are desired, then the proposed 192s/176p dual star–delta winding machine is the best choice, with the stator power only 2.6% less than that of the baseline ISW machine, but unfortunately still has significant rotor and PM eddy current losses.

Wire arc additive manufacturing (WAAM) technology enables the fabrication of functionally graded materials (FGMs) by adjusting the wire feed speed of different welding wires in a layer-by-layer manner. This study aimed to produce SS 316L/Inconel 625 FGMs with varying transition compositions using dual-wire arc additive manufacturing (D-WAAM). An optimization strategy for transition gradients was implemented to exclude component regions that are prone to defect formation (notably cracking), as well as to retain other component regions, thereby enhancing the overall mechanical properties of FGMs. The study revealed grain boundary cracking and demonstrated the lowest microhardness and tensile properties within a 20 wt.% Inconel 625 transition gradient zone, which negatively impacts the overall mechanical properties of FGMs. Then, as the content of Inconel 625 in the first transition region increased, cracks disappeared, microhardness increased and better tensile properties were obtained. The most optimal mechanical properties were enriched at 50 wt.% Inconel 625 content. In conclusion, the compositional gradient optimization strategy proves efficacious in eliminating component regions with poor mechanical properties and microdefects, ensuring excellent overall mechanical characteristics of FGMs.

SHP2, a pivotal component downstream of both receptor and non-receptor tyrosine kinases, has been underscored in the progression of various human cancers and neurodevelopmental disorders. Allosteric inhibitors have been proposed to regulate its autoinhibition. However, oncogenic mutations, such as E76K, convert SHP2 into its open state, wherein the catalytic cleft becomes fully exposed to its ligands. This study elucidates the dynamic properties of SHP2 structures across different states, with a focus on the effects of oncogenic mutation on two known binding sites of allosteric inhibitors. Through extensive modeling and simulations, we further identified an alternative allosteric binding pocket in solution structures. Additional analysis provides insights into the dynamics and stability of the potential site. In addition, multi-tier screening was deployed to identify potential binders targeting the potential site. Our efforts to identify a new allosteric site contribute to community-wide initiatives developing therapies using multiple allosteric inhibitors to target distinct pockets on SHP2, in the hope of potentially inhibiting or slowing tumor growth associated with SHP2.