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AIM: To describe the characteristics of peripapillary hyperreflective ovoid mass-like structure (PHOMS) in myopic children and to investigate factors associated with PHOMS. METHODS: This retrospective observational study included 101 eyes of 101 children (age ≤17y) with myopia. All included patients underwent comprehensive clinical examination. Optic nerve canal parameters, including disc diameter, optic nerve head (ONH) tilt angle, and border tissue angle were measured using serial enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Based on the optic disc drusen consortium's definition of PHOMS, eyes were classified as PHOMS group and non-PHOMS group. PHOMS was categorized according to height. RESULTS: Sixty-seven (66.3%) eyes were found with PHOMS. Small PHOMS could only be detected by optical coherence tomography (OCT). Medium PHOMS could be seen with blurred optic disc borders corresponding to OCT. The most frequent location of PHOMS was at the nasosuperior (91%, 61 of 67 eyes) to ONH disc. The axial length and spherical equivalent were more myopic in the PHOMS group than in the non-PHOMS group (both P

Background: Hypoxic pulmonary hypertension (HPH) is the main pathological change in vascular remodeling, a complex cardiopulmonary disease caused by hypoxia. Some research results have shown that ginsenoside Rg1 (Rg1) can improve vascular remodeling, but the effect and mechanism of Rg1 on hypoxia-induced pulmonary hypertension are not clear. The purpose of this study was to discuss the potential mechanism of action of Rg1 on HPH. Methods: C57BL/6 mice, calpain-1 knockout mice and Pulmonary artery smooth muscle cells (PASMCs) were exposed to a low oxygen environment with or without different treatments. The effect of Rg1 and calpain-1 silencing on inflammation, fibrosis, proliferation and the protein expression levels of calpain-1, STAT3 and p-STAT3 were determined at the animal and cellular levels. Results: At the mouse and cellular levels, hypoxia promotes inflammation, fibrosis, and cell proliferation, and the expression of calpain-1 and p-STAT3 is also increased. Ginsenoside Rg1 administration and calpain-1 knockdown, MDL-28170, and HY-13818 treatment showed protective effects on hypoxia-induced inflammation, fibrosis, and cell proliferation, which may be associated with the downregulation of calpain-1 and p-STAT3 expression in mice and cells. In addition, overexpression of calpain 1 increased p-STAT3 expression, accelerating the onset of inflammation, fibrosis and cell proliferation in hypoxic PASMCs. Conclusion: Ginsenoside Rg1 may ameliorate hypoxia-induced pulmonary vascular remodeling by suppressing the calpain-1/STAT3 signaling pathway.

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was

The family is the first classroom for children and adolescents to learn and grow, and parents’ behavior plays an important role in influencing their children’s development, which is also evident in the process of sport participation. The main purpose of this study is to summarise the specific theoretical and practical experiences of parents in sport parenting based on a comprehensive review of the types and functions that constitute parental involvement in sport parenting and the process of their practice. To this end, this study used narrative research as the main research method and searched the literature related to parents’ involvement in parenting through sport using the Web of Science database. Using the theoretical underpinnings of parents’ implementation of sport parenting and their role practice, studies were screened and 39 pieces of literature were finally obtained. The study found that in terms of theoretical underpinnings, the existing types of parental involvement in sport parenting can be broadly categorized into four types: authoritative, authoritarian, permissive and rejecting-neglecting. The functions of parental involvement in sport education have two dimensions: promoting sport development and promoting socialization. Based on a review of their theories, we further summarise and conclude the consequences of action and appropriate practices of parental practices in three scenarios: on the sports field, on the way home and in the private space. It is assumed that parents, when participating in sports parenting, need to: (I) regulate their own behavior in order to avoid psychological pressure on their children due to inappropriate behavior; (II) play different roles at different stages of their children’s sports development; (III) should not put too much pressure on their children’s performance. Based on these reviews of the theory and practice of parental involvement in sport parenting, this study further examines the theoretical limitations of the established research. It is argued that future research should pay attention to the differences between the identities and expectations of parents or children of different genders about their sport parenting, in addition to the differences in parental involvement in sport parenting and different practices in different cultural contexts.

Photocatalytic reactions, achieving chemical synthesis in a more sustainable manner than thermal reactions, have been demonstrated to become more efficient, greener and easier to scale up when combined with continuous microflow technology. Nevertheless, the report on the kinetics measurement for photocatalytic reactions in continuous microflow, especially in a fully automated way, is very rare. In this work, two challenging parameters, i.e., the reaction order with respect to oxygen (2.48) and photoreaction activation energy (-16.83 kJ/mol) of the photocatalytic oxidation of 9,10-diphenylanthracene, were acquired in an automated continuous flow platform using the Steady-state Method. Moreover, the Ramping Method was also successfully implemented in the automated continuous flow photoreaction platform, exhibiting a predictive accuracy of 4.42 %, with 64.3 % less time and 58.0 % less material consumption than the Steady-state Method. And it was found that the improvement in the residence time distribution of the microreactor could improve the accuracy of the Ramping Method. The automated continuous flow process developed in this work could offer an efficient and accurate way to attain the reaction kinetics information for homogeneous photocatalytic reactions.

Objective To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. Methods High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. Results The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. Conclusion ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

The miscibility of flue gas and different types of light oils is investigated through slender-tube miscible displacement experiment at high temperature and high pressure. Under the conditions of high temperature and high pressure, the miscible displacement of flue gas and light oil is possible. At the same temperature, there is a linear relationship between oil displacement efficiency and pressure. At the same pressure, the oil displacement efficiency increases gently and then rapidly to more than 90% to achieve miscible displacement with the increase of temperature. The rapid increase of oil displacement efficiency is closely related to the process that the light components of oil transit in phase state due to distillation with the rise of temperature. Moreover, at the same pressure, the lighter the oil, the lower the minimum miscibility temperature between flue gas and oil, which allows easier miscibility and ultimately better performance of thermal miscible flooding by air injection. The miscibility between flue gas and light oil at high temperature and high pressure is more typically characterized by phase transition at high temperature in supercritical state, and it is different from the contact extraction miscibility of CO2 under conventional high pressure conditions.

Abstract Background There has been a significant surge in the global prevalence of diabetes mellitus (DM), which increases the susceptibility of individuals to ovarian cancer (OC). However, the relationship between DM and OC remains largely unexplored. The objective of this study is to provide preliminary insights into the shared molecular regulatory mechanisms and potential biomarkers between DM and OC. Methods Multiple datasets from the GEO database were utilized for bioinformatics analysis. Single cell datasets from the GEO database were analysed. Subsequently, immune cell infiltration analysis was performed on mRNA expression data. The intersection of these datasets yielded a set of common genes associated with both OC and DM. Using these overlapping genes and Cytoscape, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then conducted on these core targets. Additionally, advanced bioinformatics analyses were conducted to construct a TF-mRNA-miRNA coregulatory network based on identified core targets. Furthermore, immunohistochemistry staining (IHC) and real-time quantitative PCR (RT-qPCR) were employed for the validation of the expression and biological functions of core proteins, including HSPAA1, HSPA8, SOD1, and transcription factors SREBF2 and GTAT2, in ovarian tumors. Results The immune cell infiltration analysis based on mRNA expression data for both DM and OC, as well as analysis using single-cell datasets, reveals significant differences in mononuclear cell levels. By intersecting the single-cell datasets, a total of 119 targets related to mononuclear cells in both OC and DM were identified. PPI network analysis further identified 10 hub genesincludingHSP90AA1, HSPA8, SNRPD2, UBA52, SOD1, RPL13A, RPSA, ITGAM, PPP1CC, and PSMA5, as potential targets of OC and DM. Enrichment analysis indicated that these genes are primarily associated with neutrophil degranulation, GDP-dissociation inhibitor activity, and the IL-17 signaling pathway, suggesting their involvement in the regulation of the tumor microenvironment. Furthermore, the TF-gene and miRNA-gene regulatory networks were validated using NetworkAnalyst. The identified TFs included SREBF2, GATA2, and SRF, while the miRNAs included miR-320a, miR-378a-3p, and miR-26a-5p. Simultaneously, IHC and RT-qPCR reveal differential expression of core targets in ovarian tumors after the onset of diabetes. RT-qPCR further revealed that SREBF2 and GATA2 may influence the expression of core proteins, including HSP90AA1, HSPA8, and SOD1. Conclusion This study revealed the shared gene interaction network between OC and DM and predicted the TFs and miRNAs associated with core genes in monocytes. Our research findings contribute to identifying potential biological mechanisms underlying the relationship between OC and DM.

A flexible and stable optical fiber sensor based on the Sagnac loop is proposed and experimentally demonstrated for the measurement of salinity and temperature, simultaneously. The sensing unit consists of a tapered polarization maintaining fiber (tPMF) and a fiber Bragg grating (FBG) connected in series in the Sagnac loop. The temperature response comes from the high birefringence of PMF inside Sagnac loop, and the salinity response is enabled by the high-order modes excited in the tapered area of PMF. Besides, the FBG is for temperature compensation. We have succeeded in implementing dual-parameter measurements with the sensitivities of 0.356 nm/‰ for salinity and 0.616 nm/°C for temperature, respectively. The designed sensor has the potential for long-term monitoring of real ocean states.

Objective To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). Methods Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4+ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. Results CD4+ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4+ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/106 CD4+ T cell′s respectively. Conclusion The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

SiC/Cu composites were prepared by hot-pressing powder metallurgy with Al and Mg elements, and the effect of SiC volume percentage on the properties of SiC/Cu composites was studied. X-ray diffraction, Archimedes drainage method, three-point bending method and scanning electron microscope were used to analyze the phase composition, relative density, mechanical properties and micro-morphology of the composite samples, and the thermal conductivity and thermal expansion coefficient were measured. The thermal expansion coefficient of the composite was predicted by ROM mixing law and Turner model. Experimental results show that AlCuMg phase is formed in the matrix of the sample, and the strength is greatly increased, and the mixed fracture is the main type of the sample. The SiC particles are uniformly dispersed in the matrix when the SiC content is low. The density, bending strength, thermal conductivity and thermal expansion coefficient of SiC/Cu composites are 98.81%, 478 MPa, 254.76 W/(m·K) and 11.84 × 10−6/K respectively when the SiC content is 35%. When the content of SiC increases, the agglomeration of SiC particles is serious, and the density, bending strength, thermal conductivity and thermal expansion coefficient of the composites decrease. Its hardness increases at first and then decreases, and reaches the maximum value of 110 HRB when the SiC content is 45%. The Turner model is the closest to the measured values of composites.

In order to investigate the mechanism of extracellular polysaccharide (EPS) synthesis in Lactobacillus plantarum, a strain of Lactobacillus plantarum YZH81 with high EPS production was selected for the study of extracellular polysaccharide synthesis gene cluster (cps). After whole-genome sequencing, alignment and analysis, it was determined that the genome of YZH81 contained two cps gene clusters, one of which (cps1) had yet to be identified in terms of structure and function, while the other (cps2) was highly homologous to other reported Lactobacillus plantarum strains. The conclusions in this study, the cps1 gene cluster resulted 52.28% reduction in EPS production, accelerated self-aggregation, reduced adhesion and 32.42% reduction in the ability to generated 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH·) in the YZH81∆cps1 strain compared to the wild-type YZH81 strain. The results suggested that the cps1 gene cluster of strain YZH81 was associated with EPS synthesis and established favorable conditions for further studies on the mechanism of EPS biosynthesis in this strain.

Aquatic biodiversity monitoring relies on species recognition from images. While deep learning (DL) streamlines the recognition process, the performance of these method is closely linked to the large-scale labeled datasets, necessitating manual processing with expert knowledge and consume substantial time, labor, and financial resources. Semi-supervised learning (SSL) offers a promising avenue to improve the performance of DL models by utilizing the extensive unlabeled samples. However, the complex collection environments and the long-tailed class imbalance of aquatic species make SSL difficult to implement effectively. To address these challenges in aquatic species recognition within the SSL scheme, we propose a Wavelet Fusion Network and the Consistency Equilibrium Loss function. The former mitigates the influence of data collection environment by fusing image information at different frequencies decomposed through wavelet transform. The latter improves the SSL scheme by refining the consistency loss function and adaptively adjusting the margin for each class. Extensive experiments are conducted on the large-scale FishNet dataset. As expected, our method improves the existing SSL scheme by up to 9.34% in overall classification accuracy. With the accumulation of image data, the improved SSL method with limited labeled data, shows the potential to advance species recognition for aquatic biodiversity monitoring and conservation.

Abstract Microgravity is one of the most common causes counting for the bone loss. Mesenchymal stem cells (MSCs) contribute greatly to the differentiation and function of bone related cells. The development of novel MSCs biomarkers is critical for implementing effective therapies for microgravity induced bone loss. We aimed to find the new molecules involved in the differentiation and function of MSCs in mouse simulated microgravity model. We found CD226 was preferentially expressed on a subset of MSCs. Simulation of microgravity treatment significantly increased the proportion of CD226+Lin−CD117−Sca1+ MSCs. The CD226+ MSCs produced higher IL‐6, M‐CSF, RANKL and lower CD200 expression, and promoted osteoclast differentiation. This study provides pivotal information to understand the role of CD226 in MSCs, and inspires new ideas for prevention of bone loss related diseases.

SiCp/Al composites were prepared by hot-pressing sintering method, and the effect of sintering temperature on the properties of the composites was studied. The phase compositions, relative density, mechanical properties and micro morphology of the composite samples were analyzed through X-ray diffraction, Archimedes drainage method, the three-point bending method and scanning electron microscope. Additionally, the thermal conductivity and thermal expansion coefficient were measured. The results show that SiCp/Al composites are composed of SiC, Al and Mg2Si phases. The addition of Mg improves the wettability between the matrix and SiC particles. With the increase of sintering temperature, the hardness and bending strength of the composites first increase and then decrease, reaching the maximum values of 98 HRB and 275 MPa at 700 ℃, respectively. The thermal conductivity of the composites first increases and then decreases, and the thermal expansion coefficient first decreases and then increases, reaching the maximum value of 218.187 W/(m·K) and the minimum value of 8.6 × 10−6 K−1 at 700 ℃, respectively.

Abstract Aim To explore the status quo of self‐management among young adults with type 2 diabetes mellitus (T2DM) and the determinants of self‐management under the guidance of social cognitive theory. Design A cross‐sectional study. Methods In total, 227 young adults (18–44 years old) with T2DM at two hospitals in Beijing completed the questionnaires. The Summary of Diabetes Self‐care Activities (SDSCA) was used, along with additional questionnaires about diabetes self‐efficacy, attitude, diabetes distress, diabetes knowledge, coping styles and social support. Univariate analysis and multiple linear regression were used to explore the related factors of self‐management among the young patients. Results The scores for the SDSCA in diet, exercise, blood‐glucose testing, foot care and medication taking were (4.16 ± 1.51), (3.46 ± 2.50), (2.28 ± 2.24), (1.08 ± 1.84) and (6.09 ± 1.88), respectively. Stepwise multiple linear regression showed that fasting blood‐glucose value was significantly associated with self‐management behaviours of diet, exercise, blood‐glucose testing and medication taking. Self‐efficacy was significantly associated with self‐management behaviours of diet, exercise and foot care. Diabetes distress, diabetes‐related social activity, confrontation, education, duration of T2DM, treatment modalities and diabetes knowledge were associated with the one or two dimensions of SDSCA in the young adults with T2DM.

The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse β-fold (residues 441–456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors.

The dopaminergic system is susceptible to dysfunction in numerous neurological diseases, including Parkinson’s disease (PD). In addition to motor symptoms, some PD patients may experience non-motor symptoms, including cognitive and memory deficits. A possible explanation for their manifestation is a disturbed pattern of dopamine release in brain regions involved in learning and memory, such as the hippocampus. Therefore, investigating neuropathological alterations in dopamine release prior to neurodegeneration is imperative. This study aimed to characterize evoked hippocampal dopamine release and assess the impact of the neurotoxin MPP+ using a genetically encoded dopamine sensor and gene expression analysis. Additionally, considering the potential neuroprotective attributes demonstrated by apoptosis signal-regulating kinase 1 (Ask1) in various animal-disease-like models, the study also aimed to determine whether Ask1 knockdown restores MPP+-altered dopamine release in acute hippocampal slices. We applied variations of low- and high-frequency stimulation to evoke dopamine release within different hippocampal regions and discovered that acute application of MPP+ reduced the amount of dopamine released and hindered the recovery of dopamine release after repeated stimulation. In addition, we observed that Ask1 deficiency attenuated the detrimental effects of MPP+ on the recovery of dopamine release after repeated stimulation. RNA sequencing analysis indicated that genes associated with the synaptic pathways are involved in response to MPP+ exposure. Notably, Ask1 deficiency was found to downregulate the expression of Slc5a7, a gene encoding a sodium-dependent high-affinity choline transporter that regulates acetylcholine levels. Respective follow-up experiments indicated that Slc5a7 plays a role in Ask1 deficiency-mediated protection against MPP+ neurotoxicity. In addition, increasing acetylcholine levels using an acetylcholinesterase inhibitor could exacerbate the toxicity of MPP+. In conclusion, our data imply that the modulation of the dopamine-acetylcholine balance may be a crucial mechanism of action underlying the neuroprotective effects of Ask1 deficiency in PD.

Extreme climate events can have severe impacts on both vegetation and the carbon cycle. However, whether land management exacerbates or mitigates the effects of extreme climate events on vegetation remains unknown. We investigated the case of an extreme precipitation event that occurred in a region dominated by double–cropping (DC) systems located in the Yangtze–Huai plain in China. Waterlogging disasters were triggered by an extreme precipitation event in October 2016, which severely affected the sowing and seedling emergence of winter crops (mainly winter wheat). The lack of sowing and low seedling emergence rate subsequently led to months of low growth, as evidenced by negative enhanced vegetation index (EVI) anomalies, especially from March to May 2017. Local agricultural meteorological monthly reports, government announcements, and winter wheat data based on statistics and remote sensing confirmed the reduced yields. The influence on vegetation ended in June 2017, when summer crops were planted. Our results demonstrate that, in such a DC system, when extreme events occur during the key sowing period, the impacts will continue through the entire crop growth period, until the next sowing. More generally, agricultural land management could extend the duration and magnitude of the impacts of extreme climate events on vegetation.

Abstract Deformable superstructures are man‐made materials with large deformation properties that surpass those of natural materials. However, traditional deformable superstructures generally use conventional materials as substrates, limiting their applications in multi‐mode reconfigurable robots and space‐expandable morphing structures. In this work, amine‐acrylate‐based liquid crystal elastomers (LCEs) are used as deformable superstructures substrate to provide high driving stress and strain. By changing the molar ratio of amine to acrylate, the thermal and mechanical properties of the LCEs are modified. The LCE with a ratio of 0.9 exhibited improved polymerization degree, elongation at break, and toughness. Besides an anisotropic finite deformation model based on hyperelastic theory is developed for the LCEs to capture the configuration variation under temperature activation. Built upon these findings, an LCE‐based paper‐cutting structure with negative Poisson's ratio and a 2D lattice superstructure model are combined, processed, and molded by laser cutting. The developed superstructure is pre‐programmed to the configuration required for service conditions, and the deformation processes are analyzed using both experimental and finite element methods. This study is expected to advance the application of deformable superstructures and LCEs in the fields of defense and military, aerospace, and bionic robotics.

Primary and acquired therapy resistance is a major problem in patients with BRAF-mutant melanomas being treated with BRAF and MEK inhibitors (BRAFI, MEKi). Therefore, development of alternative therapy regimes is still required. In this regard, new drug combinations targeting different pathways to induce apoptosis could offer promising alternative approaches. Here, we investigated the combination of proteasome and Kv1.3 potassium channel inhibition on chemo-resistant, BRAF inhibitor-resistant as well as sensitive human melanoma cells. Our experiments demonstrated that all analyzed melanoma cell lines were sensitive to proteasome inhibitor treatment at concentrations that are not toxic to primary human fibroblasts. To further reduce proteasome inhibitor-associated side effects, and to foster apoptosis, potassium channels, which are other targets to induce pro-apoptotic effects in cancer cells, were blocked. In support, combined exposure of melanoma cells to proteasome and Kv1.3 channel inhibitor resulted in synergistic effects and significantly reduced cell viability. On the molecular level, enhanced apoptosis correlated with an increase of intracellular Kv1.3 channels and pro-apoptotic proteins such as Noxa and Bak and a reduction of anti-apoptotic proteins. Thus, use of combined therapeutic strategies triggering different apoptotic pathways may efficiently prevent the outgrowth of drug-resistant and -sensitive BRAF-mutant melanoma cells. In addition, this could be the basis for an alternative approach to treat other tumors expressing mutated BRAF such as non-small-cell lung cancer.

Taking the construction management of green water conservancy projects combined with BIM as the research background, we analyzed the application of BIM technology in green construction management. The results also showed that the overall trend of green construction management research is on the rise, the research on green construction management at home and abroad is relatively close, and the research directions tend to be intelligent and informative, but there is relatively little research on water conservancy engineering. Combining the current green construction standards of water conservancy projects, the related literature, and the current situation of the application of BIM technology in water conservancy project construction management, the concept of green construction of water conservancy projects and the core requirements of BIM technology for whole-life-cycle green construction are proposed. The new green construction technology was applied in combination with BIM to form a collaborative and scaled multiparty management structure map for the whole process area, build a framework system for green construction management of water conservancy projects, and design a specific implementation process for the application of real-time green construction simulation systems in BIM.

In order to determine the influence of measurement rack on local airflow deflection angle of the direction field in low-speed wind tunnel flow field calibration, the design parameters of different measurement racks were studied by numerical simulations. By comparing the numerical simulations and test results under the same working conditions, the effectiveness of the numerical calculation method was verified. Based on the verified numerical calculation method, influence para-meters such as blocking degree of measurement rack, distance from the center line of test section, installation angle and length of the test probe on the measurement of local airflow deflection angle were studied. The corresponding influence law was obtained, and the influence model was established. The results show that the rack blocking degree, distance from the center line of test section, installation angle and length of the test probe have obvious effects on test angle of local airflow deflection angle. If the test design or test method is improper, it will directly lead to a large error in test results, and ultimately affect the accuracy of the direction field quality evaluation results.

Abstract Background Laparoscopic surgery has been a milestone for minimally invasive surgeries. But safe removal of large uterine tissue is a challenge for minimally invasive procedures, and there still exists concern about the dissemination of benign or occult malignant uterine tissue during the use of the morcellator. Different tissue containment systems have been used in laparoscopic power morcellation. However, a risk of leakage still exists in clinical practice. In this study, we aimed to evaluate leakage and tissue dissemination associated with a new detachable multi-hard-port containment system for tissue removal during laparoscopic myomectomy morcellation. Methods Beef tongue specimens were stained with methylene blue solution and morcellated in a plastic trainer box under laparoscopic guidance. The morcellation test in vitro conditions comprised two different containment systems to simulate laparoscopic power morcellation, specifically a polyurethane bag with two pipes (control group) and a detachable multi-hard-port containment system (experimental group). Insufflation pressure was set at 14 mmHg. Three methods are used to detect the leakage The procedure times were recorded. Thirty trials were performed using a multi-port approach and the two tissue containment systems. Results The leakage rate was 0.03% (n = 30) for the experimental group and 26.6% (n = 30) for the control group (p

Abstract For comprehensive studies of the brain structure and function, fluorescence imaging of the whole brain is essential. It requires large-scale volumetric imaging in cellular or molecular resolution, which could be quite challenging. Recent advances in tissue clearing technology (e.g. CLARITY, PACT) provide new solutions by homogenizing the refractive index of the samples to create transparency. However, it has been difficult to acquire high quality results through immunofluorescence (IF) staining on the cleared samples. To address this issue, we developed TSA-PACT, a method combining tyramide signal amplification (TSA) and PACT, to transform samples into hydrogel polymerization frameworks with covalent fluorescent biomarkers assembled. We show that TSA-PACT is able to reduce the opacity of the zebrafish brain by more than 90% with well-preserved structure. Compared to traditional method, TSA-PACT achieves approximately tenfold signal amplification and twofold improvement in signal-to-noise ratio (SNR). Moreover, both the structure and the fluorescent signal persist for at least 16 months with excellent signal retention ratio. Overall, this method improves immunofluorescence signal sensitivity, specificity and stability in the whole brain of juvenile and adult zebrafish, which is applicable for fine structural analysis, neural circuit mapping and three-dimensional cell counting.

Abstract Oral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine remains the most effective treatment for Parkinson’s disease (PD). However, unlike the continuous and steady dopamine signaling in normal neurons, oral Dopa induces dramatic fluctuations in plasma Dopa levels, leading to Dopa-induced dyskinesia. Herein, we report a functional nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production. FNA-Fe3O4 can cross the blood-brain barrier and target diseased neurons relying on transferrin receptor aptamer. Then, FNA-Fe3O4 responds to overexpressed α-synuclein mRNA in diseased neurons for antisense oligonucleotide treatment and fluorescence imaging, while converting to tyrosine aptamer-based artificial enzyme (Apt-Fe3O4) that mimics tyrosine hydroxylase for in situ continuous Dopa production. In vivo FNA-Fe3O4 treatment results in recovery of Dopa and dopamine levels and decrease of pathological overexpressed α-synuclein in PD mice model, thus ameliorating motor symptoms and memory deficits. The presented functional nucleic acid-based responsive artificial enzyme strategy provides a more neuron friendly approach for the diagnosis and treatment of PD.

Abstract Background Despite the extensive research on data mining algorithms, there is still a lack of a standard protocol to evaluate the performance of the existing algorithms. Therefore, the study aims to provide a novel procedure that combines data mining algorithms and simplified preprocessing to establish reference intervals (RIs), with the performance of five algorithms assessed objectively as well. Methods Two data sets were derived from the population undergoing a physical examination. Hoffmann, Bhattacharya, Expectation Maximum (EM), kosmic, and refineR algorithms combined with two-step data preprocessing respectively were implemented in the Test data set to establish RIs for thyroid-related hormones. Algorithm-calculated RIs were compared with the standard RIs calculated from the Reference data set in which reference individuals were selected following strict inclusion and exclusion criteria. Objective assessment of the methods is implemented by the bias ratio (BR) matrix. Results RIs of thyroid-related hormones are established. There is a high consistency between TSH RIs established by the EM algorithm and the standard TSH RIs (BR = 0.063), although EM algorithms seems to perform poor on other hormones. RIs calculated by Hoffmann, Bhattacharya, and refineR methods for free and total triiodo-thyronine, free and total thyroxine respectively are close and match the standard RIs. Conclusion An effective approach for objectively evaluating the performance of the algorithm based on the BR matrix is established. EM algorithm combined with simplified preprocessing can handle data with significant skewness, but its performance is limited in other scenarios. The other four algorithms perform well for data with Gaussian or near-Gaussian distribution. Using the appropriate algorithm based on the data distribution characteristics is recommended.

Abstract Background This study aimed to develop cardiovascular disease (CVD) risk equations for Chinese patients with newly diagnosed type 2 diabetes (T2D) to predict 10-, 20-, and 30-year of risk. Methods Risk equations for forecasting the occurrence of CVD were developed using data from 601 patients with newly diagnosed T2D from the Da Qing IGT and Diabetes Study with a 30-year follow-up. The data were randomly assigned to a training and test data set. In the training data set, Cox proportional hazard regression was used to develop risk equations to predict CVD. Calibration was assessed by the slope and intercept of the line between predicted and observed probabilities of outcomes by quintile of risk, and discrimination was examined using Harrell’s C statistic in the test data set. Using the Sankey flow diagram to describe the change of CVD risk over time. Results Over the 30-year follow-up, corresponding to a 10,395 person-year follow-up time, 355 of 601 (59%) patients developed incident CVD; the incidence of CVD in the participants was 34.2 per 1,000 person-years. Age, sex, smoking status, 2-h plasma glucose level of oral glucose tolerance test, and systolic blood pressure were independent predictors. The C statistics of discrimination for the risk equations were 0.748 (95%CI, 0.710–0.782), 0.696 (95%CI, 0.655–0.704), and 0.687 (95%CI, 0.651–0.694) for 10-, 20-, and 30- year CVDs, respectively. The calibration statistics for the CVD risk equations of slope were 0.88 (P = 0.002), 0.89 (P = 0.027), and 0.94 (P = 0.039) for 10-, 20-, and 30-year CVDs, respectively. Conclusions The risk equations forecast the long-term risk of CVD in patients with newly diagnosed T2D using variables readily available in routine clinical practice. By identifying patients at high risk for long-term CVD, clinicians were able to take the required primary prevention measures.

Aim of study: Understanding the carbon budget and meteorological factor impacts of farmland ecosystems is helpful for scientific assessment of carbon budget and low-carbon agricultural production practices. Area of study: The Songnen Plain, NE China, in 2019. Material and methods: Based on eddy-related flux and soil heterotrophic respiration observations from a typical maize farmland ecosystem, using mathematical statistics and carbon balance equation methods, were analyzed. Main results: Soil respiration rate (Rs) and composition were influenced and controlled by the synergistic effect of surface soil temperature (Ts) and water content (Wcs). Ts played a leading role, while Wcs played an important role. Ts and Wcs had the greatest influence on the heterotrophic respiration rate (Rh), followed by Rs and autotrophic respiration rate (Ra). Daily variations of net ecosystem productivity were correlated with daily mean air temperature, latent heat flux, and sensible heat flux. Annual carbon revenue was 1139.67 g C m-2, annual carbon expenditure was 456.14 g C m-2, and annual carbon budget was -683.53 g C m-2 in 2019. While considering that maize grain yield (-353.44 g C m-2) was moved out of the field at harvest, the net ecosystem carbon balance was -330.09 g C m-2; then it was carbon sink in 2019. By fully utilizing climate resources and improving agricultural managements, carbon sink is increased in farmland ecosystems. Research highlights: Soil respiration rate and composition were influenced and controlled by the synergistic effect of soil temperature and water content; the maize farmland ecosystem is carbon sink.

Angiogenesis plays a key role in the pathological process of inflammation and invasion of the synovium, and primarily drives the progression of rheumatoid arthritis (RA). Recent studies have demonstrated that the Notch signaling may represent a new therapeutic target of RA. Although the Notch signaling has been implicated in the M1 polarization of macrophages and the differentiation of lymphocytes, little is known about its role in angiogenesis in RA. In this review, we discourse the unique roles of stromal cells and adipokines in the angiogenic progression of RA, and investigate how epigenetic regulation of the Notch signaling influences angiogenesis in RA. We also discuss the interaction of the Notch-HIF signaling in RA’s angiogenesis and the potential strategies targeting the Notch signaling to improve the treatment outcomes of RA. Taken together, we further suggest new insights into future research regarding the challenges in the therapeutic strategies of RA.

ABSTRACT Purpose: To investigate the Shikonin (SHI) induce autophagy of hypertrophic scar-derived fibroblasts (HSFs) and the mechanism of which in repairing hypertrophic scar. Methods: This study showed that SHI induced autophagy from HSFs and repaired skin scars through the AMPK/mTOR pathway. Alamar Blue and Sirius red were used to identify cell activity and collagen. Electron microscopy, label-free quantitative proteomic analysis, fluorescence and other methods were used to identify autophagy. The differences in the expression of autophagy and AMPK/mTOR pathway-related proteins after SHI treatment were quantitatively analyzed by Western blots. A quantitative real-time polymerase chain reaction assay was used to detect the expression of LC3, AMPK and ULK after adding chloroquine (CQ) autophagy inhibitor. Results: After treatment with SHI for 24 hours, it was found that the viability of HSFs was significantly reduced, the protein expression of LC3-II/LC3-I and Beclin1 increased, while the protein expression of P62 decreased. The expression of phosphorylated AMPK increased and expression of phosphorylated mTOR decreased. After the use of CQ, the cell autophagy caused by SHI was blocked. The key genes LC3 and P62 were then reexamined by immunohistochemistry using a porcine full-thickness burn hypertrophic scar model, and the results verified that SHI could induce autophagy in vivo. Conclusions: These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.

BackgroundWith the early initiation of antiretroviral therapy (ART) in China, the demographics of treatment-naïve people living with HIV (PLWH) are moving closer to those of the general population, which is characterized by a gradual increase in metabolic indicators. However, the epidemic trends of overweight and obesity over the past decade in treatment-naïve PLWH ready to initiate ART have not yet been investigated.MethodsA cross-sectional study was conducted, including 12,135 consecutive treatment-naïve PLWH ready to initiate ART in Shenzhen, using data retrieved from the China National Free Antiretroviral Treatment Program database from 2014 to 2020. The chi-square test was used to examine the trends of overweight and obesity between age groups, and multivariate logistic regression was used to identify the association of overweight and obesity with hyperglycemia and dyslipidemia.ResultsDuring the 7-year study period, 12,135 treatment-naïve PLWH ready to initiate ART were included, among whom 1,837 (15.1%) were overweight and 388 (3.2%) were obese. The prevalence of overweight rose from 11.4 to 17.3% (Z = −4.58, P for trend 35 years compared to prevalence in other age groups during the period 2014–2020. Compared with those who were not overweight or obese, PLWH who were overweight or obese were more likely to have hyperglycemia (aOR 1.84, 95% CI: 1.37–2.49 for overweight; aOR 2.68, 95% CI: 1.62–4.44 for obesity), higher ALT level (aOR 2.70, 95% CI: 2.33–3.13 for overweight; aOR 3.85, 95% CI: 2.93–5.05 for obesity), higher TG levels (aOR 1.89, 95% CI 1.63–2.19 for overweight; aOR 2.56, 95% CI 1.97–3.32 for obesity), and lower HDL levels (aOR 1.67, 95% CI 1.44–1.95 for overweight; aOR 2.06, 95% CI 1.54–2.77 for obesity).ConclusionThe prevalence of overweight and obesity in treatment-naive PLWH increased steadily from 2014 to 2020 in Shenzhen. Overweight and obese in treatment-naive PLWH ready to initiate ART were associated with dyslipidemia and hyperglycemia. Public health authorities should take proactive steps to address these issues by implementing targeted screening, intervention programs including lifestyle modifications, and integrated healthcare services.

Perinatal exposure to bifenthrin (BF) alters neurodevelopment. However, the most susceptible time period to BF exposure and the possible mechanisms are not clear. In the current study, pregnant female mice were treated with BF (0.5 mg/kg/d) at three different stages [gestational day (GD) 0–5, 6–15 and 16-birth (B)] and neurologic deficits were evaluated in offspring mice. BF exposure at GD 16-B significantly altered the locomotor activity and caused learning and memory impairments in 6-week-old offspring. Gestational BF exposure also caused neuronal loss in the region of cornu ammonis of hippocampi of 6-week-old offspring. Interestingly, neurobehavioral impairments and neuronal loss were not observed in offspring at 10-week-old. BF exposure at GD 16-B also decreased protein levels of VGluT1, NR1 and NR2A while increased the protein levels of NR2B and VGAT1, as well as the gene levels of Il-1β, Il-6 and Tnf-α in hippocampi of 6-week-old offspring. Collectively, these data demonstrate that gestational exposure to a low dose BF causes neurodevelopmental deficits that remit with the age and the late-stage of pregnancy is the most susceptible time window to BF exposure. Imbalance in excitatory/inhibitory neuronal transmission, altered expression levels of NMDA receptors and increased neural inflammation may be associated with BF prenatal exposure-triggered neurobehavioral impairments.

The use of oral agents that can modify the gut microbiota (GM) could be a novel preventative or therapeutic option for Parkinson’s disease (PD). Maslinic acid (MA), a pentacyclic triterpene acid with GM-dependent biological activities when it is taken orally, has not yet been reported to be effective against PD. The present study found both low and high dose MA treatment significantly prevented dopaminergic neuronal loss in a classical chronic PD mouse model by ameliorating motor functions and improving tyrosine hydroxylase expressions in the substantia nigra pars compacta (SNpc) and increasing dopamine and its metabolite homovanillic acid levels in the striatum. However, the effects of MA in PD mice were not dose-responsive, since similar beneficial effects for low and high doses of MA were observed. Further mechanism studies indicated that low dose MA administration favored probiotic bacterial growth in PD mice, which helped to increase striatal serotonin, 5-hydroxyindole acetic acid, and γ-aminobutyric acid levels. High dose MA treatment did not influence GM composition in PD mice but significantly inhibited neuroinflammation as indicated by reduced levels of tumor necrosis factor alpha and interleukin 1β in the SNpc; moreover, these effects were mainly mediated by microbially-derived acetic acid in the colon. In conclusion, oral MA at different doses protected against PD via distinct mechanisms related to GM. Nevertheless, our study lacked in-depth investigations of the underlying mechanisms involved; future studies will be designed to further delineate the signaling pathways involved in the interactive actions between different doses of MA and GM.

Abstract Traffic accident prediction on road levels and minute levels plays an important role in optimizing public safety and improving traffic infrastructure. However, there are still some challenges in this work. Firstly, the dynamic factors (e.g. traffic flow) affecting traffic accidents make the road network have dynamic spatio‐temporal dependency, which leads to biased prediction results. Secondly, the occurrence of traffic accidents is a small probability event, which brings about zero‐inflation problem. To address aforementioned problems, the authors propose a Multi‐Attention Dynamic Graph Convolution Network with Cost Sensitive Learning approach (MADGCN). Specifically, in the spatial dimension, MADGCN calculates the attention scores of different types of dynamic factors through attention mechanism to simulate the different influence degrees of different factors, and models dynamic inter‐road spatial correlation through Graph Convolution Network (GCN). In the temporal aspect, MADGCN adaptively models the dynamic temporal correlations through self‐attention blocks. In addition, MADGCN improves the loss function based on cost‐sensitive learning strategy to increase the cost of false classification of positive samples, so as to accurately mine sparse positive samples. Experimental results on two real‐world traffic accident datasets demonstrate the superiority of MADGCN. Compared with the existing state‐of‐the‐art methods, F1‐score of MADGCN on two real‐world traffic accident datasets is improved by 11.61% and 9.15%, respectively.

Background: Taxane-induced peripheral neuropathy (TIPN) is a debilitating adverse effect of cancer treatments with taxanes which may require a reduction or discontinuation chemotherapy and affect clinical and survival outcomes. A number of factors have contributed to the increasing prevalence of TIPN. Nonetheless, limited knowledge exists of potential prechemotherapy blood-based biochemical factors associated with TIPN development. Methods: We recruited breast cancer patients at seven cancer institutions in China. Participants aged 18 years or older with stage I to III breast cancer who scheduled to undergo primary neoadjuvant and adjuvant chemotherapy with taxanes were eligible. Eligible patients underwent patient-reported neuropathy assessments using the EORTC-CIPN20 questionnaire. Patients completed the questionnaire before commencing treatment and after every cycle. For every patient, we selected the highest TIPN toxicity score for analysis since the first cycle. The posttreatment TIPN severity was compared with blood-based biochemical factors within 30 days before commencing treatment. Independent samples t tests, Mann-Whitney U tests and linear regression were used to identify blood-based and clinical associations with TIPN development. Results: The study included 873 breast cancer participants who received paclitaxel, docetaxel or nanoparticle albumin-bound (nab)-paclitaxel. In the whole cohort, factors associated with higher TIPN toxicity scores were higher cumulative chemotherapy dose (β = 0.005; 95% CI, 0.004 to 0.006; P

Background: As the major pathophysiological feature of obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) is vital for the occurrence of cardiovascular complications. The activation of calpain-1 mediates the production of endothelial reactive oxygen species (ROS) and impairs nitric oxide (NO) bioavailability, resulting in vascular endothelial dysfunction (VED). Ginsenoside Rg1 is thought to against endothelial cell dysfunction, but the potential mechanism of CIH-induced VED remains unclear. Methods: C57BL/6 mice and human coronary artery endothelial cells (HCAECs) were exposed to CIH following knockout or overexpression of calpain-1. The effect of ginsenoside Rg1 on VED, oxidative stress, mitochondrial dysfunction, and the expression levels of calpain-1, PP2A and p-eNOS were detected both in vivo and in vitro. Results: CIH promoted VED, oxidative stress and mitochondrial dysfunction accompanied by enhanced levels of calpain-1 and PP2A and reduced levels of p-eNOS in mice and cellular levels. Ginsenoside Rg1, calpain-1 knockout, OKA, NAC and TEMPOL treatment protected against CIH-induced VED, oxidative stress and mitochondrial dysfunction, which is likely concomitant with the downregulated protein expression of calpain-1 and PP2A and the upregulation of p-eNOS in mice and cellular levels. Calpain-1 overexpression increased the expression of PP2A, reduced the level of p-eNOS, and accelerated the occurrence and development of VED, oxidative stress and mitochondrial dysfunction in HCAECs exposed to CIH. Moreover, scavengers of O2• −, H2O2, complex Ⅰ or mitoKATP abolished CIH-induced impairment in endothelial-dependent relaxation. Conclusion: Ginsenoside Rg1 may alleviate CIH-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.

Dynamic fault tree (DFT) and its related research methods have received extensive attention in safety analysis and reliability engineering. DFT can perform reliability modelling for systems with sequential correlation, resource sharing, and cold and hot spare parts. A technical modelling method of DFT is proposed for modelling ship collision accidents and loss-of-coolant accidents (LOCAs). Qualitative and quantitative analyses of DFT were carried out using the cutting sequence (CS)/extended cutting sequence (ECS) method. The results show nine types of dynamic fault failure modes in ship collision accidents, describing the fault propagation process of a dynamic system and reflect the dynamic changes of the entire accident system. The probability of a ship collision accident is 2.378 × 10−9 by using CS. This failure mode cannot be expressed by a combination of basic events within the same event frame after an LOCA occurs in a marine nuclear reactor because the system contains warm spare parts. Therefore, the probability of losing reactor control was calculated as 8.125 × 10−6 using the ECS. Compared with CS, ECS is more efficient considering expression and processing capabilities, and has a significant advantage considering cost.

Background: Several studies scatteredly identified the myelodysplastic syndromes’ transcriptomic profiles (MDS). However, the exploration of transcriptional signatures, key signalling pathways, and their association with prognosis and diagnosis in the integrated multiple datasets remains lacking. Methods: We integrated the GSE4619, GSE19429, GSE30195, and GSE58831 microarray datasets of CD34 + cells for identifying the differentially expressed genes (DEGs) in the MDS. The series of bioinformatics methods are applied to identify the key hub genes, gene clusters, prognostic hub genes, and genes associated with diagnostic efficacy. Finally, we validated the expression differences of hub genes in the GSE114922 dataset. Results: We explored the DEGs related to gene ontology enrichment and KEGG pathways. We identified significant hub genes, including 168 upregulated hub genes (such as STAT1, IFIH1, EPRS, GRB2, RAC2, MAPK14, CASP1, and SPI1) and 52 downregulated hub genes (such as CREBBP, HIF1A, PIK3CA, EZH2, PIK3R1, MDM2, IRF4, CXCR4, PCNA, and CD19) in the MDS. In addition, we identified six significant molecular complex detection (MCODE)-derived upregulated gene clusters and one downregulated gene cluster, respectively. Moreover, we found that the higher expression level of MX2, GBP2, PXN, IFI44, FDXR, PLCB2, ASS1, ERCC4, PML, and RRAGD and the lower expression level of CD19, PAX5, TCF3, LEF1, NUSAP1, and TIMELESS hub genes are significantly correlated with shorter survival times of MDS patients. Furthermore, the area value under the ROC curve (AUC) of PXN, FDXR, PLCB2, PML, CD19, PAX5, and LEF1 prognostic genes are more than 0.80, indicating that these genes could be effectively used for the diagnostic efficacy of MDS patients. Conclusions: Identifying key hub genes and their association with the prognosis and diagnostic efficacy may provide substantial clues for the treatment and diagnosis of MDS patients.

The deregulation of microRNAs (miRNAs) and genes in the bone marrow microenvironment have been involved with the pathogenesis of multiple myeloma (MM). However, the exploration of miRNA-mRNA regulatory networks in MM remains lacking. We used GSE125363, GSE125361, GSE47552, GSE2658, GSE136324, GSE16558, and GSE13591 datasets for this bioinformatics study. We identified 156 downregulated and 13 upregulated differentially expressed miRNAs (DEmiRs) in MM. The DEmiRs are associated with the enrichment of pathways mainly involved with cancers, cellular signaling, and immune regulations. We identified 112 hub genes associated with five significant clusters in MM. Moreover, we identified 9 upregulated hub genes (such as IGF1, RPS28, UBA52, CDKN1A, and CDKN2A) and 52 downregulated hub genes (such as TP53, PCNA, BRCA1, CCNB1, and MSH2) in MM that is targeted by DEmiRs. The expression of DEmiRs targeted two hub genes (CDKN2A and TP53) are correlated with the survival prognosis of MM patients. Furthermore, the expression level of CDKN2A is correlated with immune signatures, including CD4+ Regulatory T cells, T cell exhaustion, MHC Class I, immune checkpoint genes, macrophages, neutrophils, and TH2 cells in the TME of MM. Finally, we revealed the consistently deregulated expression level of key gene CDKN2A and its co-regulatory DEmiRs, including hsa-mir-192, hsa-mir-10b, hsa-mir-492, and hsa-mir-24 in the independent cohorts of MM. Identifying key genes and miRNA-mRNA regulatory networks may provide new molecular insights into the tumor immune microenvironment in MM.

Despite being a non-hematophagous leech, Whitmania pigra is widely used in traditional Chinese medicine for the treatment of antithrombotic diseases. In this study, we provide a high quality genome of W. pigra and based on which, we performed a systematic identification of the potential antithrombotic genes and their corresponding proteins. We identified twenty antithrombotic gene families including thirteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. Unexpectedly, a total of 79 antithrombotic genes were identified, more than a typical blood-feeding Hirudinaria manillensis, which had only 72 antithrombotic genes. In addition, combining with the RNA-seq data of W. pigra and H. manillensis, we calculated the expression levels of antithrombotic genes of the two species. Five and four gene families had significantly higher and lower expression levels in W. pigra than in H. manillensis, respectively. These results showed that the number and expression level of antithrombotic genes of a non-hematophagous leech are not always less than those of a hematophagous leech. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a non-hematophagous leech to date and will significantly enhance the investigation and utilization of leech derivatives in thrombosis therapy research and pharmaceutical applications.

The hippocampal formation, particularly the CA2 subregion, is critical for social memory formation and memory processing, relying on synaptic plasticity—a fundamental mechanism by which synapses strengthen. Given the role of the ubiquitin–proteasome system (UPS) in various nervous system processes, including learning and memory, we were particularly interested in exploring the involvement of RING-type ubiquitin E3 ligases, such as UHRF2 (NIRF), in social behavior and synaptic plasticity. Our results revealed altered social behavior in mice with systemic Uhrf2 knockout, including changes in nest building, tube dominance, and the three-chamber social novelty test. In Uhrf2 knockout mice, the entorhinal cortex-CA2 circuit showed significant reductions in synaptic plasticity during paired-pulse facilitation and long-term potentiation, while the inability to evoke synaptic plasticity in the Schaffer-collateral CA2 synapses remained unaffected. These changes in synaptic plasticity correlated with significant changes in gene expression including genes related to vesicle trafficking and transcriptional regulation. The effects of Uhrf2 knockout on synaptic plasticity and the observed gene expression changes highlight UHRF2 as a regulator of learning and memory processes at both the cellular and systemic levels. Targeting E3 ubiquitin ligases, such as UHRF2, may hold therapeutic potential for memory-related disorders, warranting further investigation.

Carcinoembryonic antigen (CEACAM5), as a broad-spectrum tumor biomarker, plays a crucial role in analyzing the therapeutic efficacy and progression of cancer. Herein, we propose a novel biosensor based on specklegrams of tapered multimode fiber (MMF) and two-dimensional convolutional neural networks (2D-CNNs) for the detection of CEACAM5. The microfiber is modified with CEA antibodies to specifically recognize antigens. The biosensor utilizes the interference effect of tapered MMF to generate highly sensitive specklegrams in response to different CEACAM5 concentrations. A zero mean normalized cross-correlation (ZNCC) function is explored to calculate the image matching degree of the specklegrams. Profiting from the extremely high detection limit of the speckle sensor, variations in the specklegrams of antibody concentrations from 1 to 1000 ng/mL are measured in the experiment. The surface sensitivity of the biosensor is 0.0012 (ng/mL)−1 within a range of 1 to 50 ng/mL. Moreover, a 2D-CNN was introduced to solve the problem of nonlinear detection surface sensitivity variation in a large dynamic range, and in the search for image features to improve evaluation accuracy, achieving more accurate CEACAM5 monitoring, with a maximum detection error of 0.358%. The proposed fiber specklegram biosensing scheme is easy to implement and has great potential in analyzing the postoperative condition of patients.

BackgroundFalls are serious health events that can cause life-threatening injuries, especially among specific populations. This study assessed the risk factors associated with falls among inpatients with hematological diseases and explored the predictive value of fall risk assessment models.MethodsClinical data from 275 eligible hematology disease patients who visited Mianyang Central Hospital with or without falls from September 2019 to August 2022 were retrospectively analyzed. Fall risk scores were determined in all included patients. Clinical characteristics were compared between patients with and without falls. Binary logistic regression models were used to screen for potential fall-specific risk factors among hospitalized patients with hematology diseases.ResultsFalls occurred in 79 cases. Patients in the fall group had a higher Charlson Comorbidity Index (CCI), a higher incidence of diabetes mellitus, visual impairment, hematological malignancies, and maintenance of stable disease stage, higher glucose levels, and a greater proportion of dizziness, nocturnal defecation, and receipt of intensive chemotherapy than those in the non-fall group (all P < 0.05). Fall patients were also more likely to have used diuretics, laxatives, sedative-sleeping drugs, analgesics, albumin, and calcium, and to have had catheters placed. The Barthel Index, grade of nursing care, support of chaperones, body temperature, nutrition score, and pain score also differed significantly between the two groups (all P < 0.05). Multivariable logistic regression analysis showed that the maintenance of stable disease stage (OR = 4.40, 95% CI 2.11–9.18, P < 0.001), use of sedative and sleeping drugs (OR = 4.84, 95% CI 1.09–21.49, P = 0.038), use of diuretics (OR = 5.23, 95% CI 2.40–11.41, P < 0.001), and intensive chemotherapy (OR = 10.41, 95% CI 3.11–34.87, P < 0.001) were independent risk factors for falls. A high Barthel Index (OR = 0.95, 95% CI 0.93–0.97, P < 0.001), a high level of nursing care (OR = 0.19, 95% CI 0.04–0.98, P = 0.047), and availability of family accompaniment (OR = 0.15, 95% CI 0.06–0.34, P < 0.001) were protective factors for falls. A ROC curve analysis was used to evaluate the predictive value of different fall-specific risk scales among inpatients with hematological diseases. The Johns Hopkins Fall Risk Rating Scale had high sensibility and specificity with an area under the curve of 0.73 (95% CI 0.66–0.80, P < 0.001).ConclusionThe Johns Hopkins Fall Risk Scale had a strong predictive value for falls among hospitalized patients with hematology diseases and can be recommended as a valid tool for clinical use.

Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB’s hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas’ high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.

Abstract. Background:. Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen. Methods:. This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People's Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed. Results:. Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q1–Q3: 24.0–34.0 years); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only. Conclusions:. Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.

Abstract Machine learning methods are a novel way to predict and rank donors' willingness to donate blood and to achieve precision recruitment, which can improve the recruitment efficiency and meet the challenge of blood shortage. We collected information about experienced blood donors via short message service (SMS) recruitment and developed 7 machine learning-based recruitment models using PyCharm-Python Environment and 13 features which were described as a method for ranking and predicting donors’ intentions to donate blood with a floating number between 0 and 1. Performance of the prediction models was assessed by the Area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score in the full dataset, and by the accuracy in the four sub-datasets. The developed models were applied to prospective validations of recruiting experienced blood donors during two COVID-19 pandemics, while the routine method was used as a control. Overall, a total of 95,476 recruitments via SMS and their donation results were enrolled in our modelling study. The strongest predictor features for the donation of experienced donors were blood donation interval, age, and donation frequency. Among the seven baseline models, the eXtreme Gradient Boosting (XGBoost) and Support vector machine models (SVM) achieved the best performance: mean (95%CI) with the highest AUC: 0.809 (0.806–0.811), accuracy: 0.815 (0.812–0.818), precision: 0.840 (0.835–0.845), and F1 score of XGBoost: 0.843 (0.840–0.845) and recall of SVM: 0.991 (0.988–0.994). The hit rate of the XGBoost model alone and the combined XGBoost and SVM models were 1.25 and 1.80 times higher than that of the conventional method as a control in 2 recruitments respectively, and the hit rate of the high willingness to donate group was 1.96 times higher than that of the low willingness to donate group. Our results suggested that the machine learning models could predict and determine the experienced donors with a strong willingness to donate blood by a ranking score based on personalized donation data and demographical details, significantly improve the recruitment rate of blood donors and help blood agencies to maintain the blood supply in emergencies.

Abstract Aims/Introduction To estimate the prevalence, and patient clinical and demographic profile, as well as risk factors associated with obstructive sleep apnea syndrome (OSAS) in hospitalized patients with type 2 diabetes mellitus in Beijing, China. Materials and Methods Hospitalized adult patients with type 2 diabetes mellitus were consecutively screened and invited for an overnight polysomnography from four hospitals in Beijing, China, from May 2016 to February 2017. We used the American Academy of Sleep Medicine 2012 polysomnography recording techniques and scoring criteria to identify the type of apnea and the severity of OSAS. The χ2‐test was used to evaluate differences between groups regarding the prevalence, and demographic and other clinical parameters. Results A total of 735 patients were found eligible for the study, of whom 309 patients completed the overnight polysomnography. The mean age of the patients was 58.2 ± 10.9 years, and most (67.3%) were men. The prevalence of overall (apnea hypopnea index ≥5/h), moderate‐to‐severe (apnea hypopnea index ≥15/h) and severe (apnea hypopnea index ≥30/h) OSAS was 66.3% (95% confidence interval 60.8–71.6%), 35.6% (95% confidence interval 30.3–41.2%) and 16.5% (95% confidence interval 12.5–21.1%), respectively. Central and mixed apnea contributed 12% to all sleep‐disordered breathing. With the aggravation of OSAS, the combined prevalence for central, mixed and obstructive apnea increased from 57% to 70%. We found OSAS to be associated with older age, obesity, self‐reported snoring and apnea, and diabetes complications. Conclusions Guidelines on screening and treatment of OSAS among hospitalized patients with diabetes are needed to direct the routine practice for diabetes endocrinologists for optimal clinical care of such patients.