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Cadmium (Cd) is among the most available and most toxic heavy metals taken up by plants from soil. Compared to the classic plant-animal food chains, the host-parasitic plant food chains have, thus far, been largely overlooked in the studies of Cd trophic transfer. To investigate the pattern of Cd transfer during the infection of parasitic plants on Cd-contaminated hosts, we conducted a controlled experiment that grew soybeans parasitized by Chinese dodders (Cuscuta chinensis) in soil with different levels of Cd treatment, and examined the concentration, accumulation, allocation and transfer coefficients of Cd within this parasitic system. Results showed that among all components, dodders accounted for more than 40% biomass of the whole system but had the lowest Cd concentration and accumulated the least amount of Cd. The transfer coefficient of Cd between soybean stems and dodders was much lower than 1, and was also significantly lower than that between soybean stems and soybean leaves. All these features were continuously strengthened with the increase of Cd treatment levels. The results suggested no evidence of Cd biomagnification in dodders parasitizing Cd-contaminated hosts, and implied that the Cd transfer from hosts to dodders may be a selective process.

Seed dispersal plays critical roles in determining species survival and community structures. Since the dispersal is biologically under maternal control, it is hypothesized that intraspecific variation of dispersal potential and associated traits of seeds (diaspores) should be influenced by maternal habitat quality. We tested this hypothesis by examining the effects of maternal environmental light condition on morphological traits and descending performance of nearly 1800 wind-dispersed samaras collected from maple species Acer palmatum. Results showed that samaras produced by trees from shaded microhabitats had greater dispersal potential, in terms of slower terminal velocity of descent, than those produced in open microhabitats. This advantage was largely attributed to morphological plasticity. On average, samaras produced in shaded microhabitats, as compared to those produced in open habitats, had lower wing loading by only reducing weight but not area. In allometric details, in the large size range, samaras from shaded microhabitats had larger areas than those from open microhabitats; in the small size range, samaras from shaded microhabitats had wider wings. These findings suggest that greater dispersal potential of samaras in response to stressful maternal light environment reflected an active maternal control through the morphological allometry of samaras.

Abstract Recent studies have demonstrated that plants can determine the identity of neighbouring roots (e.g., self and non-self, kin and non-kin), but whether they can discriminate by sex remains an open question. Here, we predict that dioecious plants can modulate their root performance in response to local root conditions related to sex. Female and male Populus cathayana cuttings were planted in a greenhouse in root-owner (one individual without a root neighbour) or root-sharer pairs (two individuals with roots neighbouring each other) with equal amounts of nutrients and space per plant in three combinations (females–females, males–males or females–males); root morphology, biomass and allocation were investigated. P. cathayana root-sharers altered their root growth in same-sex but not in different-sex combinations. Females enhanced root growth and allocation but decreased root proliferation (greater diameter with reduced branching and specific root length) in the presence of a female root neighbour, while males reduced root growth but increased root morphological proliferation in contact with another male. Therefore, the effect of a neighbour of the same sex differed from that of a neighbour of the opposite sex, which suggests that these plants can recognize the sexual identity of their neighbours.

Plants can detect the presence of their neighbors belowground, often responding with changes in root growth for resource competition. Recent evidence also implies that perception of neighbors may also elicit defense responses, however, the associated metabolic activities are unclear. We investigated primary and defense-related secondary metabolisms and hormone expressions in tobaccos (Nicotiana rustica) grown either with own roots or roots of another conspecifics in hydroponic condition. The results showed that non-self root interaction significantly reduced photosynthetic activity and assimilate production, leading to a reduction of growth. Non-self interaction also modified plant phenylpropanoids metabolism, yielding higher lignin content (i.e., structural resistance) at whole plant level and higher phenolics accumulation (i.e., chemical defense) in roots. All these metabolic responses were associated with enhanced expressions of phytohormones, particularly jasmonic acid, salicylic acid and cytokinin in roots and abscisic acid in leaves, at the early stage of non-self interaction. Since the presence of neighbors often increase the probability of attacks from, e.g., pathogens and pests, this defense activation may act as an adaptation of plants to these possible upcoming attacks.

Yunbin Xiao,1,* Zuan Tao Lin,2,* Yanmei Chen,1 He Wang,1 Ya Li Deng,2 D Elizabeth Le,3 Jianguo Bin,1 Meiyu Li,1 Yulin Liao,1 Yili Liu,1 Gangbiao Jiang,2 Jianping Bin1 1State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People’s Republic of China; 3Cardiovascular Division, Oregon Health and Science University, Portland, OR, USA *These authors contributed equally to this work Abstract: Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors. Keywords: superparamagnetic iron oxide, magnetic resonance imaging, polymeric micelles, folate receptors, tumor-targeted MRI, N-palmitoyl chitosan

High power short-pulse lasers presently reach peak powers of a few hundred Terawatts up to a Petawatt, and routinely reach focal intensities of 1018 - 1021 W/cm2 . These lasers are able to produce various secondary radiation, from relativistic electrons and multi-MeV/nucleon ions to high-energetic X-rays and γ-rays. In many laboratories world-wide large efforts are presently devoted to a rapid development of this novel tool of particle acceleration, targeting nuclear, fundamental and high-field physics studies as well as various applications. Based on the Radiation Pressure Acceleration mechanism, laser-accelerated ion beams can be generated with solid-state density, thus exceeding beams from conventional accelerators by about 14 orders of magnitudes. This opens the perspective of a novel reaction scheme called ’f ssion-fusion’, where in a first step f ssion is induced both in laser-accelerated f ssile projectiles from a ’production target’ and in a second ’reaction target’ again from f ssile material hit by the accelerated projectiles. Due to the unprecedented ion density, (neutron-rich) light f ssion fragments from projectile and target can fuse again, forming extremely exotic species approaching the region of the N = 126 waiting point of the r-process. Within the next 5 years a new EU-funded large-scale research infrastructure (ELI: Extreme Light Infrastructure) will be constructed, with one of its four pillars exclusively devoted to nuclear physics based on high intensity lasers (ELI-Nuclear Physics, to be built in Magurele/Bucharest). Studies of laser-induced nuclear reactions like the ’f ssion-fusion’ mechanism will be amongst the experimental f agship projects pursued there.

Access to finance is perceived as one of the major problems facing businesses in Sub-Saharan Africa, as well as the structures that support them in their development. This paper aims to measure the probability that a support structure with given characteristics, specific services to entrepreneurs and some technical capacities will face large-scale financial problems. We estimate a multinomial logistic model using a pool of disaggregated data collected by the Nkafu Policy Institute in a survey of 80 business support structures in Burkina Faso, Cameroon and Ghana in 2021. Our results show that the financial health of a business support structure is not fundamentally dependent on the duration of support, but rather on other factors related to the quality of services offered to entrepreneurs. [ABSTRACT FROM AUTHOR]

Abstract Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P

Abstract Embryonal carcinoma (EC), characterized by a high degree of stemness similar to that of embryonic stem cells, is the most malignant subtype within non-seminomatous testicular germ cell tumors (TGCTs). However, the mechanisms underlying its malignancy remain unknown. In this study, we employed single-cell RNA sequencing to analyze four non-seminoma samples. Our differential expression analysis revealed high expression of SERPINB9 in metastatic EC cells. We conducted in vitro experiments to further investigate SERPINB9’s role in the progression of EC. Functionally, the knockdown of SERPINB9 in NCCIT and NTERA-2 leads to a diminished migratory capability and decreased cis-platin resistance, as demonstrated by Transwell migration assay and drug sensitivity assay. Moreover, embryoid bodies showed reduced size and lower OCT4 expression, alongside heightened expression of differentiation markers AFP, ACTA2, and CD57 in shSERPINB9 cells. In vivo, the role of SERPINB9 in maintaining cancer stemness was validated by the limiting dilution assay. Mechanistically, Bulk RNA-seq further showed downregulation of ERK1/2 signaling and WNT signaling pathways with concomitant upregulation of differentiation pathways subsequent to SERPINB9 knockdown. Additionally, the analysis indicated increased levels of cytokines linked to tertiary lymphoid structures (TLS), such as IL6, IL11, IL15, CCL2, CCL5, and CXCL13 in shSERPINB9 cells, which were further validated by ELISA. Our research indicates that SERPINB9 plays a key role in driving tumor progression by enhancing tumor stemness and suppressing TLS. This study stands as the first to elucidate the molecular signature of non-seminomas at a single-cell level, presenting a wealth of promising targets with substantial potential for informing the development of future therapeutic interventions.

Abstract Clinical proteomics analysis is of great significance for analyzing pathological mechanisms and discovering disease-related biomarkers. Using computational methods to accurately predict disease types can effectively improve patient disease diagnosis and prognosis. However, how to eliminate the errors introduced by peptide precursor identification and protein identification for pathological diagnosis remains a major unresolved issue. Here, we develop a powerful end-to-end deep learning model, termed “MS1Former”, that is able to classify hepatocellular carcinoma tumors and adjacent non-tumor (normal) tissues directly using raw MS1 spectra without peptide precursor identification. Our model provides accurate discrimination of subtle m/z differences in MS1 between tumor and adjacent non-tumor tissue, as well as more general performance predictions for data-dependent acquisition, data-independent acquisition, and full-scan data. Our model achieves the best performance on multiple external validation datasets. Additionally, we perform a detailed exploration of the model’s interpretability. Prospectively, we expect that the advanced end-to-end framework will be more applicable to the classification of other tumors.

V and Cr bimetals are utilized as interlayers in the vacuum diffusion bonding of TA2 Ti and 20# steel to prevent the formation of Ti–Fe intermetallic compounds and improve the interface compatibility. The microstructure and mechanical properties of the diffusion-bonded joints are investigated using optical microscopy, scanning electron microscopy combined with energy dispersive spectroscopy, transmission electron microscopy, X-ray diffraction, nanoindentation, and tensile testing. The results indicate that the V/Cr bimetallic interlayer effectively inhibits the formation of Ti–Fe intermetallic compounds, with solid solutions without these compounds present at the Ti/V and steel/Cr interfaces. However, a 1–3-μm-thick continuous, hard, brittle vanadium carbide layer with hardness and elastic modulus value of 6.66 GPa and 201.55 GPa is unexpectedly discovered at the interface between V and Cr. The fracture morphology analysis reveals that the continuous carbide layer at the V/Cr interface is the primary cause of joint failure. The tensile strength of the joint remains relatively stable with an increase in the bonding temperature, whereas the elongation gradually decreases. A maximum tensile strength of 252 MPa is achieved with an elongation of 4.3%.

The AlN particles reinforced Mg-10Gd-3Y–1Zn (GWZ) composites were prepared by mixing AlN/Al particles using ball milling followed by stirring casting method. The influence of AlN/Al particles on the microstructural evolution and high-temperature mechanical properties of GWZ alloys were revealed and discussed. With AlN/Al particles added into the as-cast alloys, the Mg3RE phase was transformed into lamellar LPSO phase, while the content of Al2RE and LPSO phase increased. Since the Al2RE and AlN were effective nucleation sites for α-Mg, the grain size of AlN/Al-GWZ composites was reduced obviously from 126.1 to 39.8 μm. After homogenization, due to the coherent lattice matching relationships between 18R-LPSO phase and Al2RE or AlN particles, the 18R-LPSO phase nucleated on the Al2RE and AlN particles. After ageing treatment, the 2AlN/Al-GWZ composite showed the optimum mechanical properties at 250 °C, with the yield strength, ultimate tensile strength and elongation of 247.1 MPa, 265.5 MPa and 4.0%, respectively. The strengthening effect was primarily originated from the AlN particles, Al2RE and LPSO phases in the 2AlN/Al-GWZ composite. Besides, the composites can achieve the enhancement of high-temperature strength without the sacrifice of plasticity due to the coordinated deformation of AlN particles as well as the refinement of grains.

Abstract Background Thymoma is a primary tumor of the thymus, commonly located in the anterior mediastinum. Most thymomas are benign or low‐grade malignant, but they can invade surrounding organs or metastasize. The primary treatment for thymoma is surgical resection. Traditional methods involve open thoracotomy, but it is traumatic, with slow recovery and many complications. In recent years, with the development of thoracoscopic techniques, thoracoscopic total thymectomy has gradually become the preferred method for small size thymomas due to its minimally invasive, safe, and effective. Methods This paper introduces a thoracoscopic extend thymectomy technique, the subxiphoid video–assisted thoracoscopic extend thymectomy with sternal suspension. This method involves placing hooks at the upper and lower ends of the sternum to suspend the sternum upward, increasing the thoracic cavity space and facilitating thoracoscopic operations. This research reviews the clinical data of 59 patients with early‐stage thymomas treated with this technique at our center since 2020 and analyzes the perioperative therapeutic efficacy and safety. It also compares the outcomes with those of 17 patients who underwent thoracoscopic approaches. Results The results show that subxiphoid video–assisted thoracoscopic total thymectomy with sternal suspension is an innovative and effective surgical method, achieving the same tumor eradication as other thoracic surgeries. The flexible switching of observation ports provides a more comprehensive surgical field, reduces surgical trauma and complications, and improves the surgical outcomes and quality of life for patients.

Solubility enhancement of poorly aqueous-soluble drugs, like Terbinafine (TBN), is a critical challenge in formulating effective dosage forms. This study focused on developing β-cyclodextrin (β-CD) and polyacrylamide (PAM)-based microgels to address the solubility issue of TBN, classified as a biopharmaceutics classification system class II drug. The microgels were crafted through free radical polymerization, employing methylene bisacylamide as a cross-linker and methacrylic acid as a monomer, initiated by ammonium persulfate. Comprehensive characterizations, including Fourier transform infrared, thermo-gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, powder X-ray diffractometry analysis, Zeta size, and Zeta potential, were conducted. In vitro studies, such as drug release and swelling, were performed at pH 1.2. Toxicity analysis in rabbits revealed zero toxicity. These β-CD/PAM microgels successfully enhanced the solubility of TBN.

Androgen‐regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone‐sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)‐homology splicing regulatory protein known as far upstream element‐binding protein 2 (KHSRP) is an RNA‐binding protein that can attach to AU‐rich elements in the 3′ untranslated region (3′‐UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen‐regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP‐regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA‐seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD‐dependent protein deacetylase sirtuin‐7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP‐regulated mRNA decay of the DDR‐related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration‐resistant PCa.

Mg–3Y/Al composites were produced through accumulated rolling bonding. During annealing, Al–Y precipitates were synthesized in-situ within the Mg–3Y/Al composites through solid diffusion reactions. In these composites, the volume fraction of the interface layer containing abundant Al–Y precipitates can reach approximately 74% after three passes of accumulated rolling bonding and diffusion annealing. At room temperature, the Mg–3Y/Al composite exhibits increased strength (∼273.9 MPa) but reduced ductility (∼3.5%) compared to the base Mg–3Y alloy (∼191.0 MPa, ∼30%), due to the presence of numerous Al–Y precipitates and residual dislocations. These Al–Y precipitates display remarkable thermal stability, maintaining their size without significant coarsening even after annealing at 400 °C for 1–4 h, thereby contributing to the exceptional thermal stability observed in Mg–3Y/Al samples. After annealing at 400 °C for 4 h, the tensile strength of the Mg–3Y/Al samples remained unchanged, while the ductility increased to 8.5%. At 300 °C, the Mg–3Y/Al composite demonstrates exceptional high-temperature strength (179.9 MPa), significantly surpassing that of the original Mg–3Y alloy (110.6 MPa). Moreover, compared to the original Mg–3Y alloy and magnesium alloys reported in the literature, the Mg–3Y/Al composite exhibits a higher RE-equivalent strength at 300 °C. This enhanced strength is primarily attributed to precipitation strengthening induced by fine Al–Y precipitates. These findings underscore that introducing fine Al–Y precipitates through a solid diffusion reaction is an effective approach for achieving outstanding high-temperature strength in magnesium alloys.

Abstract The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD–ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.

Abstract Head pose estimation is an especially challenging task due to the complexity nonlinear mapping from 2D feature space to 3D pose space. To address the above issue, this paper presents a novel and efficient head pose estimation framework based on particle swarm optimized contrastive learning and multimodal entangled graph convolution network. Firstly, a new network, the region and difference‐aware feature pyramid network (RD‐FPN), is proposed for 2D keypoints detection to alleviate the background interference and enhance the feature expressiveness. Then, particle swarm optimized contrastive learning is constructed to alternatively match 2D and 3D keypoints, which takes the multimodal keypoints matching accuracy as the optimization objective, while considering the similarity of cross‐modal positive and negative sample pairs from contrastive learning as a local contrastive constraint. Finally, multimodal entangled graph convolution network is designed to enhance the ability of establishing geometric relationships between keypoints and head pose angles based on second‐order bilinear attention, in which point‐edge attention is introduced to improve the representation of geometric features between multimodal keypoints. Compared with other methods, the average error of our method is reduced by 8.23%, indicating the accuracy, generalization, and efficiency of our method on the 300W‐LP, AFLW2000, BIWI datasets.

Aluminum alloys have been widely used in engineering due to their high strength and low density. However, their poor corrosion and wear resistance have largely limited their application in marine equipment. This study successfully improved the corrosion and wear resistance of a typical 7075 Al alloy by depositing a high-performance TC4 titanium alloy coating using in-house annular laser cladding equipment. Microstructural investigations revealed that the defect-free TC4 coating is metallurgically bonded to the 7075 Al alloy substrate along with excellent bond strength. Electrochemical test results showed that compared to the hot-forged 7075 Al alloy and hot-forged double-phase TC4 bulk alloy, the TC4 coating exhibits superior corrosion resistance due to its net-basket α-single-phase microstructure. Further, wear testing results showed that the coefficient of friction and wear volume of the TC4 coating are far lower than that of 7075 Al alloy. The enhanced wear resistance is closely related to the high hardness of the TC4 coating and its excellent fatigue-wear resistance. Therefore, this work can serve as a reference to improve Aluminum alloys' corrosion and wear resistance by depositing Titanium alloy coatings using the annular laser cladding process, which shall widen the potential applications of Aluminum alloys in marine equipment.

Background/Aims: As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Materials and Methods: Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Results: Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Conclusion: Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Abstract Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

Abstract The concept of Yin-Yang, originating in ancient Chinese philosophy, symbolizes two opposing but complementary forces or principles found in all aspects of life. This concept can be quite fitting in the context of extracellular vehicles (EVs) and inflammatory diseases. Over the past decades, numerous studies have revealed that EVs can exhibit dual sides, acting as both pro- and anti-inflammatory agents, akin to the concept of Yin-Yang theory (i.e., two sides of a coin). This has enabled EVs to serve as potential indicators of pathogenesis or be manipulated for therapeutic purposes by influencing immune and inflammatory pathways. This review delves into the recent advances in understanding the Yin-Yang sides of EVs and their regulation in specific inflammatory diseases. We shed light on the current prospects of engineering EVs for treating inflammatory conditions. The Yin-Yang principle of EVs bestows upon them great potential as, therapeutic, and preventive agents for inflammatory diseases. Graphical Abstract

Abstract Background Children and families from priority populations experienced significant psychosocial and mental health issues to the COVID-19 pandemic. Yet they also faced significant barriers to service access, particularly families from culturally and linguistically diverse (CALD) backgrounds. With most child and family health nurse clinics ceasing in-person consultations due to the pandemic, many children missed out on health and developmental checks. The aim of this study was to investigate the perspectives and experiences of family members and service providers from an urban, CALD community regarding the implementation of a digital, developmental surveillance, Watch Me Grow-Electronic (WMG-E) program. Methods Semi-structured interviews were conducted with 17 family members, service navigators, and service providers in a multicultural community in South Western Sydney, Australia. This qualitative study is an implementation evaluation which formed as part of a larger, two-site, randomised controlled trial of the WMG-E program. A reflexive thematic analysis approach, using inductive coding, was adopted to analyse the data. Results Participants highlighted the comprehensive and personalised support offered by existing child and family health services. The WMG-E was deemed beneficial because the weblink was easy and quick to use and it enabled access to a service navigator who support family access to relevant services. However, the WMG-E was problematic because of technology or language barriers, and it did not facilitate immediate clinician involvement when families completed the weblink. Conclusions Families and service providers in this qualitative study found that using WMG-E empowered parents and caregivers to access developmental screening and learn more about their child’s development and engage with relevant services. This beds down a new and innovative solution to the current service delivery gap and create mechanisms that can engage families currently not accessing services, and increases knowledge around navigating the health and social care services. Notwithstanding the issues that were raised by families and service providers, which include accessibility challenges for CALD communities, absence of clinical oversight during screening, and narrow scope of engagement with available services being offered, it is worth noting that improvements regarding these implementation factors must be considered and addressed in order to have longevity and sustainability of the program. Trial registration. The study is part of a large randomised controlled trial (Protocol No. 1.0, Version 3.1) was registered with ANZCTR (registration number: ACTRN12621000766819) on July 21st, 2021 and reporting of the trial results will be according to recommendations in the CONSORT Statement.

Abstract Aiming at the problem that face images are easily interfered by occlusion factors in uncontrollable environments, and the complex structure of traditional convolutional neural networks leads to low expression recognition rates, slow network convergence speed, and long network training time, an improved lightweight convolutional neural network is proposed for facial expression recognition algorithm. First, the dilation convolution is introduced into the shortcut connection of the inverted residual structure in the MobileNetV3 network to expand the receptive field of the convolution kernel and reduce the loss of expression features. Then, the channel attention mechanism SENet in the network is replaced by the two-dimensional (channel and spatial) attention mechanism SimAM introduced without parameters to reduce the network parameters. Finally, in the normalization operation, the Batch Normalization of the backbone network is replaced with Group Normalization, which is stable at various batch sizes, to reduce errors caused by processing small batches of data. Experimental results on RaFD, FER2013, and FER2013Plus face expression data sets show that the network reduces the training times while maintaining network accuracy, improves network convergence speed, and has good convergence effects.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell–derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1 G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1 G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1 G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy. Graphical abstract

Mitogenome data of Odonata is accumulating and widely used in phylogenetic analysis. However, noncoding regions, especially control region, were usually omitted from the phylogenetic reconstruction. In an effort to uncover the phylogenetic insights offered by the control region, we have amassed 65 Odonata mitogenomes and conducted an examination of their control regions. Our analysis discovered that species belonging to Anisoptera and Anisozygoptera exhibited a stem-loop structure, which was formed by a conserved polyC-polyG stretch located near the rrns gene (encoding 12S rRNA). Conversely, the polyC-polyG region was not a conserved fragment in Zygoptera. The length and number of repetitions within the control region were identified as the primary determinants of its overall length. Further, sibling species within Odonata, particularly those in the genus Euphaea, displayed similar patterns of repetition in their control region. Collectively, our research delineates the structural variations within the control region of Odonata and suggests the potential utility of this region in elucidating phylogenetic relationships among closely related species.

Abstract Background The effectiveness of telemedicine in aiding rehabilitation exercises among patients with rotator cuff (RC) disorders remains unknown. Therefore, this meta-analysis aimed to assess the effectiveness of telemedicine in patients with RC disorders. Methods Randomized clinical trials (RCTs) on the effectiveness of telemedicine in patients with RC disorders were summarized through a meta-analysis. A systematic search for these RCTs was conducted in PubMed, Cochrane, Embase, and Web of Science databases up to July 2024. Statistical analysis was performed using Stata 16. Publication bias was estimated with the funnel plot and Egger’s test. Results Ten studies involving 497 participants (telemedicine group = 248 and conventional group = 249) were enrolled, with follow-up durations ranging from 8 weeks to 48 weeks. Functional outcomes measured by the Constant-Murley score were markedly improved after treatment in the telemedicine group compared to the conventional group. Moreover, compared to conventional treatment, telemedicine significantly improved shoulder function evaluated by Quick Disabilities of the Arm, Shoulder, and Hand Score, relieved pain assessed by visual analog scale pain score, and improved range of motion after treatment and in the final follow-up period. Conclusion Telemedicine has demonstrated potential in alleviating pain and enhancing shoulder function and motion in patients with RC injuries. It may be a feasible intervention for rehabilitation exercises. Further research with a large sample size and standardized treatment is warranted to validate these findings.

Abstract. Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infections. Owing to the original antigenic sin (OAS), variant breakthrough infection or vaccination potentially induces a stronger antibody response against the ancestral strain than to subsequent variants, as in the case of influenza. Thus, overcoming OAS is important for the development of future vaccine designs. This review summarizes the recent findings on OAS in the antibody response to SARS-CoV-2 and its variants, with an emphasis on future vaccine designs.

Abstract Metabolomics plays a crucial role in understanding metabolic processes within biological systems. Using specific pulse sequences, NMR-based metabolomics detects small and macromolecular metabolites that are altered in blood samples. Here we proposed a method called spectral editing neural network, which can effectively edit and separate the spectral signals of small and macromolecules in 1H NMR spectra of serum and plasma based on the linewidth of the peaks. We applied the model to process the 1H NMR spectra of plasma and serum. The extracted small and macromolecular spectra were then compared with experimentally obtained relaxation-edited and diffusion-edited spectra. Correlation analysis demonstrated the quantitative capability of the model in the extracted small molecule signals from 1H NMR spectra. The principal component analysis showed that the spectra extracted by the model and those obtained by NMR spectral editing methods reveal similar group information, demonstrating the effectiveness of the model in signal extraction.

[Introduction] Compressed air energy storage (CAES) is a technology for storing electrical energy on a large scale, only second to pumped storage in terms of scale. The gas storage device is an important component of CAES. The gas storage facilities of compressed air energy storage power plants that have been put into commercial operation domestically and abroad are mostly natural geological structures such as salt caverns and abandoned mines. Large-scale, long-term compressed air energy storage requires more economical and widely applicable gas storage facilities. [Method] Artificial underground cavern gas storage facilities largely freed compressed air energy storage power plants from the reliance on specific geological conditions, becoming a strong support for the large-scale construction of long-term compressed air energy storage power plants. However, there were few research achievements in this field domestically and internationally. Understanding the research status at home and abroad, summarizing advanced experiences from other industries, and clarifying the challenges that need to be addressed urgently in this field had significant implications for the large-scale construction of compressed air energy storage power plants. [Result] There are significant differences in the operating characteristics between artificial underground caverns in compressed air energy storage power plants and conventional artificial caverns such as natural gas storage facilities and hydroelectric water conveyance tunnels, and there is a lack of mature design methods and regulations for this field, with many technological challenges still awaiting resolution. This paper reviews the characteristics and key research contents of underground artificial caverns in compressed air energy storage power plants. [Conclusion] Prioritizing safety, considering cost-effectiveness and fostering innovation provide a guarantee for the independent development of the underground hard rock gas storage facilities for compressed air energy storage power plants. This technology holds practical significance in enriching China's energy storage and power generation experiences, and improving new power systems. If this technology matures, it can provide strong support for the construction of a new power system in China.

Mg-2.2Gd-0.4Zr sheets were prepared using transverse gradient extrusion (TGE) technology to improve their formability. The effects of different TGE processes (inclination angles of the die are 15°, 30°, 37°, 45° and 49°) on the microstructure, texture, mechanical properties, and formability of extruded sheets were researched. Furthermore, the flow behaviors of Mg-2.2Gd-0.4Zr sheets during extrusion were analyzed by the finite element simulation method. For comparison, Mg-2.2Gd-0.4Zr sheets were processed by conventional extrusion (CE) process. Results showed that the texture of TGE sheets was effectively altered. With the increase of the TGE dies tilt angle, the deviation of the basal pole in the center region of the extruded sheet towards the extrusion direction (ED) increased, while in the 1/4 edge region the basal pole deviated towards the transverse direction (TD) along the ED. The multi-type textures formed in TGE sheets are mainly attributed to the extra flow velocity along the TD and the flow gradient along the ED during extrusion. High elongation of 45.6% and low yield stress of 98.9 MPa are obtained for TGE-45 sheets. In addition, the Erichsen value (IE) of the TGE-45 sheet is 5.46 mm, which is about 47% higher than the 3.72 mm of the CE Mg-2.2Gd-0.4Zr sheet. The improved formability is due to the effective coordination of multi-directional strains during the Erichsen test for the TGE sheets.

Abstract Background The heparin sensitivity index (HSI) is closely associated with perioperative ischemic events and increased blood loss in cardiac surgery. Previous studies have produced conflicting results. Therefore, this study aimed to investigate the relationship between HSI and postoperative blood loss specifically in Chinese patients undergoing elective off-pump coronary artery bypass grafting (OPCAB). Methods Patients underwent OPCAB between March 2021 and July 2022 were retrospectively included. Enrolled patients were classified into Low-HSI (HSILOW; HSI

Mnaza Noreen,1 Muhammad Bilal,1,2 Muhammad Usman Qamar,3,4 Nasir Rasool,1 Abid Mahmood,5 Sobia Umar Din,1 Tawaf Ali Shah,6 Yousef A Bin Jardan,7 Mohammed Bourhia,8 Lahcen Ouahmane9 1Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan; 2School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, People’s Republic of China; 3Institute of Microbiology, Faculty of Life Sciences, Government College, University Faisalabad, Faisalabad, 38000, Pakistan; 4Division of Infectious Disease and Department of Medicine, University of Geneva, Geneva, Switzerland; 5Department of Pharmaceutical Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan; 6College of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo, 25500, People’s Republic of China; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 8Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, 70000, Morocco; 9Laboratory of Microbial Biotechnologies, Agrosciences and Environment (Biomage), Labeled Research Unit-CNRSTN° 4, Cadi Ayyad University, Marrakesh, 40000, MoroccoCorrespondence: Nasir Rasool; Mohammed Bourhia, Email nasirrasool@gcuf.edu.pk; m.bourhia@uiz.ac.maIntroduction: New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species.Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides ( 3a-c) by reacting 5-bromothiophene-2-sulfonamide ( 1) with various alkyl bromides ( 2) using LiH. We also synthesized a series of compounds ( 4a-g) from compound ( 3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56– 72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I.Results: The compound ( 3b) with favourable drug candidate status, MIC of 0.39 μg/mL, and MBC of 0.78 μg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions.Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option. Keywords: NDM-1, antibacterial, drug resistance, Klebsiella pneumoniae, ST, sulfonamides

For the estimation of global karst carbon sink, a few conventional methods usually require the parameters that are difficult to measure, resulting in the big cost. Moreover, under the constraints of incomplete and timeliness issues in the collection of data over a large region, it has remained a challenge for these methods to study global karst carbon sink. Therefore, this paper proposes estimating the global karst carbon sink, and analyzing the suitability of the response surface methodology and the fluctuating variation of karst carbon sink in global karst regions from 1951 to 2050. This paper shows that the proposed method can reduce the time of numerical calculation and is suitable for application in global weathering models; The global karst carbon sink in the future changes not only displays an upward trend but also exposures its fluctuating trend largely. This fluctuation is probably due to global warming.

Abstract Interactions between algae and bacteria are pivotal in transforming complex organics for microalgal-bacterial granular sludge process, but the intrinsic removal mechanisms have not been well understood. Here, we investigate the mechanisms by which complex organics are removed from municipal wastewater. Complex organics can be disposed during day-night cycles, significantly impacted by the carbon-to-nitrogen ratio in the influent. Upregulated gap2 and gpmA genes enhanced the conversion of complex organics into CO2, mediated by the interactions of Chlorophyceae with Acidobacteriae/Sumerlaeia/Fimbriimonadia, and the upregulated petH gene in Cyanobacteria strengthened the fixation of CO2 into biomass. The breakdown of starch, glycerol, and fatty acid were depended on Actinobacteriota, Chlorophyceae with Chloroflexia/Verrucomicrobiae, and Cyanobacteria with Desulfobacterota I, respectively. These findings provide new insights into the removal mechanisms of complex organics through microalgal-bacterial symbiosis and contribute to our understanding of the carbon cycle by microalgal-bacterial symbiosis in natural aquatic ecosystems.

Thermodynamic process between the ice and the ocean plays a critical role in the evolution of sea-ice growth and melting in marginal seas. At the ice-ocean interface, the oceanic heat flux and the conductive heat flux transmitted through the ice layer jointly determine the latent heat flux driving the phase change (i.e., ice freezing/melting). In this study, the determination of two important thermal parameters in the ice module of the HAMSOM ice-ocean coupled model, namely the mixed layer thickness and the heat exchange coefficient at the ice-ocean interface, has been adjusted to improve the model performance. Spatio-temporal variations of heat fluxes at the ice-ocean interface in the Bohai Sea are investigated, based on the validated sea ice simulation in the 2011/2012 ice season. The relationships between the interfacial heat fluxes and oceanic and atmospheric conditioning factors are identified. We found that the surface conductive heat flux through ice shows short-term fluctuations corresponding to the atmospheric conditions, the magnitude of these fluctuations decreases with depth in the ice layer, likely due to reduced influence from atmospheric conditions at greater depths. Atmospheric conditions are the key controlling factors of the conductive heat flux through ice, while the oceanic heat flux is mainly controlled by the oceanic conditions (i.e., mixed layer temperature). Spatially, the value of the oceanic heat flux is larger in the marginal ice zone with relatively thin ice than in the inner ice zone with relatively thick ice. In the Bohai Sea, when ice is growing, heat within the ice layer is transferred upward from the ice base, and the heat is losing at the ice-ocean interface. This heat loss in the inner ice zone is obviously greater than that in the marginal ice zone. Whereas when ice is melting, the opposite is true.