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Abstract Chemoresistance remains a significant challenge for effective breast cancer treatment which leads to cancer recurrence. CRISPR-directed gene editing becomes a powerful tool to reduce chemoresistance by reprogramming the tumor microenvironment. Previous research has revealed that Chinese herbal extracts have significant potential to overcome tumor chemoresistance. However, the therapeutic efficacy is often limited due to their poor tumor targeting and in vivo durability. Here we have developed a tumor microenvironment responsive nanoplatform (H-MnO2(ISL + DOX)-PTPN2@HA, M(I + D)PH) for nano-herb and CRISPR codelivery to reduce chemoresistance. Synergistic tumor inhibitory effects were achieved by the treatment of isoliquiritigenin (ISL) with doxorubicin (DOX), which were enhanced by CRISPR-based gene editing to target protein tyrosine phosphatase non-receptor type 2 (PTPN2) to initiate long-term immunotherapy. Efficient PTPN2 depletion was observed after treatment with M(I + D)PH nanoparticles, which resulted in the recruitment of intratumoral infiltrating lymphocytes and an increase of proinflammatory cytokines in the tumor tissue. Overall, our nanoparticle platform provides a diverse technique for accomplishing synergistic chemotherapy and immunotherapy, which offers an effective treatment alternative for malignant neoplasms. Graphical Abstract

Abstract To understand the mechanical response pattern of the existing structure and ground due to the construction of metro tunnels underneath, the finite difference method is adopted to study the torsional deformation and stress variation of the existing structure and the effect of underground carriageway structures on the surface subsidence. The curves of the maximum differential subsidence, torsion angle, and distortion of the cross‐section of the existing structure show two peaks in succession during traversing of two metro tunnels beneath it. The torsion angle of the existing structure changes when the two tunnels traverse beneath it in opposite directions. The first traversing of the shield tunnel mainly induces the magnitude variation in torsional deformation of the existing structure, but the second traversing of the subsurface tunnel may cause a dynamic change in the magnitude and form of torsional deformation in the existing structure. The shielding effect can reduce the surface subsidence caused by metro tunnel excavation to a certain extent, and the development trend of subsidence becomes slower as the excavation continues.

Targeting androgen receptor (AR) has shown great therapeutic potential in triple-negative breast cancer (TNBC), yet its efficacy remains unsatisfactory. Here, we aimed to identify promising targeted agents that synergize with enzalutamide, a second-generation AR inhibitor, in TNBC. By using a strategy for screening drug combinations based on the Sensitivity Index (SI), we found that MK-8776, a selective checkpoint kinase1 (CHK1) inhibitor, showed favorable synergism with enzalutamide in AR-positive TNBC. The combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776, respectively. Furthermore, a nanoparticle-based on hyaluronic acid (HA)-modified hollow-manganese dioxide (HMnO2), named HMnE&M@H, was established to encapsulate and deliver enzalutamide and MK-8776. This HA-modified nanosystem managed targeted activation via pH/glutathione responsiveness. HMnE&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a carrier. Collectively, our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H, providing a potential therapeutic approach for the treatment of TNBC.

Abstract Background Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. Methods The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. Results We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. Conclusions The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.

The investigation of oil and gas migration plays a vital role in the field of oil and gas exploration and development. Determining the direction and path of crude oil migration is challenging due to factors such as crude oil viscosity, complex chemical composition, and geological influences. Molecular geochemical parameters are a valuable tool for studying petroleum migration, although they can be affected by factors like compound formation, distribution, and maturation. One approach involves simulating these parameters under controlled laboratory conditions to isolate their individual effects. This study establishes a sandy-packed system to simulate oil-driven experiments and uses a C18 solid-phase extraction column to analyze carbazole compound fractions at different migration distances. The findings indicate that certain carbazole parameters, such as 1-/4-MCA, 1, 8-/1, 7-DMCA, 1, 8-/2, 4-DMCA, 1, 8-/2, 5-DMCA, and 1, 8-/2, 7-DMCA, increase significantly with transport distances. Notably, fully shielded and fully exposed isomers like 1, 8-/2, 4-DMCA and 1, 8-/2, 5-DMCA show enrichment levels of up to 63.97% and 35.50%, making them potential indicators of oil migration. However, parameters related to benzo [a]/[c] carbazole show inconsistencies with previous findings, likely due to intrinsic configurations and varying geological conditions that must be taken into account. The experimental results presented in this study offer insights for assessing specific reservoirs, with a recommendation to also consider molecular kinetics when selecting molecular parameters.

Abstract Background Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking. Methods Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (

Abstract Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Cornus officinalis, a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis, both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl4, while in vitro HSCs were exposed to transforming growth factor-β (TGF-β). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl4-induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. small interfering RNA (siRNA) experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Abstract To comprehensively understand the characteristics of the GH3 gene family in tea plants (Camellia sinensis), we identified 17 CsGH3 genes and analyzed their physicochemical properties, phylogenetic relationships, gene structures, promoters, and expression patterns in different tissues. The study showed that the 17 CsGH3 genes are distributed on 9 chromosomes, and based on evolutionary analysis, the CsGH3 members were divided into three subgroups. Gene duplication analysis revealed that segmental duplications have a significant impact on the amplification of CsGH3 genes. In addition, we identified and classified cis-elements in the CsGH3 gene promoters and detected elements related to plant hormone responses and non-biotic stress responses. Through expression pattern analysis, we observed tissue-specific expression of CsGH3.3 and CsGH3.10 in flower buds and roots. Moreover, based on predictive analysis of upstream regulatory transcription factors of CsGH3, we identified the potential transcriptional regulatory role of gibberellin response factor CsDELLA in CsGH3.14 and CsGH3.15. In this study, we found that CsGH3 genes are involved in a wide range of activities, such as growth and development, stress response, and transcription. This is the first report on CsGH3 genes and their potential roles in tea plants. In conclusion, these results provide a theoretical basis for elucidating the role of GH3 genes in the development of perennial woody plants and offer new insights into the synergistic effects of multiple hormones on plant growth and development in tea plants.

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78 × 10−7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 down-regulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

Background: The impact of climate on zoonotic infectious diseases (or can be referred to as climate-sensitive zoonotic diseases) is confirmed. Yet, research on the association between brucellosis and climate is limited. We aim to understand the impact of meteorological factors on the risk of brucellosis, especially in northeastern China. Methods: Monthly incidence data for brucellosis from 2005 to 2019 in Jilin province was obtained from the China Information System for Disease Control and Prevention (CDC). Monthly meteorological data (average temperature (°C), wind velocity (m/s), relative humidity (%), sunshine hours (h), air pressure (hPa), and rainfall (mm)) in Jilin province, China, from 2005 to 2019 were collected from the China Meteorological Information Center (http://data.cma.cn/). The Spearman's correlation was used to choose among the several meteorological variables. A distributed lag non-linear model (DLNM) was used to estimate the lag and non-linearity effect of meteorological factors on the risk of brucellosis. Results: A total of 24,921 cases of human brucellosis were reported in Jilin province from 2005 to 2019, with the peak epidemic period from April to June. Low temperature and low sunshine hours were protective factors for the brucellosis, where the minimum RR values were 0.50 (95 % CI = 0.31–0.82) for −13.7 °C with 1 month lag and 0.61 (95 % CI = 0.41–0.91) for 110.5h with 2 months lag, respectively. High temperature, high sunshine hours, and low wind velocity were risk factors for brucellosis. The maximum RR values were 2.91 (95 % CI = 1.43–5.92, lag = 1, 25.7 °C), 1.85 (95 % CI = 1.23–2.80, lag = 2, 332.6h), and 1.68 (95 % CI = 1.25–2.26, lag = 2, 1.4 m/s). The trends in the impact of extreme temperature and extreme sunshine hours on the transmission of brucellosis were generally consistent. Conclusion: High temperature, high sunshine hours, and low wind velocity are more conducive to the transmission of brucellosis with an obvious lag effect. The results will deepen the understanding of the relationship between climate and brucellosis and provide a reference for formulating relevant public health policies.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.

In response to the problem of excessive power consumption during the furrowing operation of orchard furrowing fertilizer machines, an optimization experiment of furrowing operation parameters for orchard furrowing fertilizer machine was conducted based on discrete element simulations. This research focused on the impact of furrowing device operation parameters on furrowing power consumption under full machine operating conditions. Firstly, a kinematics analysis of the soil granules during cutting was done. The mathematical model of soil granules through three movement processes of rising, detachment, and falling was established to determine the main factors affecting the power consumption of furrowing. Secondly, in assessing the furrowing power consumption, the stability coefficient of the furrowing depth, and the percentage of soil cover, alongside the key parameters of furrowing depth, forward propulsion velocity, and furrowing blade rotation speed, a comprehensive quadratic orthogonal rotation regression experiment was meticulously conducted. It was established that test metrics and test parameters regress. Finally, the test parameters were comprehensively optimized after analyzing each factor's impact on the test metrics. The orchard furrowing fertilizer machine's optimal operating parameters were determined, and the verification test was performed. According to the field test findings, the forward propulsion velocity was 785 m/h, and the furrowing blade rotation speed was 190 r/min when the furrowing depth was 275 mm. At this point, the furrowing power consumption was 2.39 kW, the soil cover percentage was 69.06%, and the furrowing depth stability coefficient was 95.08%. These results were in line with the requirements of orchard furrowing operation. The findings of the study can be utilized as a guide for structural changes to orchard furrowing equipment and the management of furrowing operation parameters.

BackgroundPrevious observational studies have demonstrated a correlation between metabolic syndrome related diseases and an elevated susceptibility to ulcers of lower limb. It has been suggested that this causal relationship may be influenced by the presence of peripheral artery disease (PAD). Nevertheless, the precise contribution of these factors as determinants of ulcers of lower limb remains largely unexplored.MethodThis research incorporated information on hypertension, BMI, hyperuricemia, type 2 diabetes, PAD, and ulcers of lower limb sourced from the GWAS database. Univariate Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to assess the association between metabolic syndrome related diseases, including hypertension, obesity, hyperuricemia, and type 2 diabetes, as well as to investigate whether this association was influenced by PAD.ResultsUnivariate Mendelian randomization analysis showed that genetically predicted hypertension, BMI, and type 2 diabetes were associated with an increased risk of PAD and ulcers of lower limb, and PAD was associated with an increased risk of ulcers of lower limb, but there is no causal relationship between hyperuricemia and ulcers of lower limb. The results of multivariate Mendelian randomization showed that PAD mediated the causal relationship between hypertension, obesity and ulcers of lower limb, but the relationship between type 2 diabetes and ulcers of lower limb was not mediated by PAD.ConclusionHypertension, BMI and type 2 diabetes can increase the risk of ulcers of lower limb, and PAD can be used as a mediator of hypertension and obesity leading to ulcers of lower limb, These findings may inform prevention and intervention strategies directed toward metabolic syndrome and ulcers of lower limb.

Users of the digital image correlation method are faced with the problem of poor operability, low repeatability, and lack of standardized specifications for spraying speckles. To solve the problem, the research proposed a rock deformation measurement method that obviates the need to spray speckles. A local binary model was established by using the local binary pattern (LBP) operator based on deep texture features on rock surfaces. The resulting LBP digital speckle pattern can substitute artificial speckle patterns and demonstrates high quality and strong applicability. Based on the LBP digital speckle pattern, the target tracking algorithm was employed to achieve non-contact measurement of the dynamic displacements of rocks. The feasibility and effectiveness of the algorithm in practical application were verified by conducting shear tests on granite and siltstone. Test results show that the deformation characteristics in the displacement nephograms are in line with the measured data pertaining to rock fracturing and conform to the basic characteristics of the shear failure of rocks. The deformation measurement method based on surface texture information can realize non-contact displacement measurement of rocks under conditions without speckles: this obviates the influence of the quality of sprayed speckles on the accuracy of the measurement of deformation.

Abstract Background Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. Methods The paraffin‐embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high‐frequency mutation genes, copy‐number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non‐metastatic groups were compared. It helped to search for potential targets. Results C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low‐grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high‐grade rectal NECs/MiNENs. These genes helped in distinguishing poorly‐differentiated or well‐differentiated rectal NENs. Alterations in P53, Wnt and TGFβ signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well‐differentiated and early‐stage tumors with less metastasis (p = 0.000). Conclusions This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high‐frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow‐up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

As urban underground spaces continue to develop, new engineering projects are increasingly closer to existing operating tunnels. This study focuses on the impact of excavation work, such as a new tunnel or deep excavation, on an existing shield tunnel. However, few studies have examined the simultaneous effects of excavation and over-crossing tunneling on operational tunnels. This paper presents a case study of Section 2 of Hangzhou Metro Line 7, employing MIDAS GTS to simulate the settlement of the existing tunnel and analyze the data collected through automatic measurements. Both methods demonstrated that excavating a foundation pit near the existing tunnel results in the tunnel’s settlement while over-crossing tunneling of the new tunnels leads to the uplift of the existing tunnel. The excavation prompted the existing tunnel to move horizontally toward the foundation pit, whereas over-crossing tunneling pushed it horizontally away. The numerical simulation revealed minor vertical displacement but significant horizontal displacement, aligning closely with the measured data. The impacts of foundation pit excavation and over-crossing tunneling on the vertical and horizontal displacement of existing tunnels are contrary, suggesting that the two construction stages will offset each other.

The exploration of catalysts for the oxygen evolution reaction (OER) with high activity and acceptable price is essential for water splitting to hydrogen generation. High-entropy materials (HEMs) have aroused increasing interest in the field of electrocatalysis due to their unusual physicochemical properties. In this work, we reported a novel FeCoNiMoZn-OH high entropy hydroxide (HEH)/nickel foam (NF) synthesized by a facile pulsed electrochemical deposition method at room temperature. The FeCoNiMoZn-OH HEH displays a 3D porous nanosheet morphology and polycrystalline structure, which exhibits extraordinary OER activity in alkaline media, including much lower overpotential (248 mV at 10 mA cm−2) and Tafel slope (30 mV dec−1). Furthermore, FeCoNiMoZn-OH HEH demonstrates excellent OER catalytic stability. The enhanced catalytic performance of the FeCoNiMoZn-OH HEH primarily contributed to the porous morphology and the positive synergistic effect between Mo and Zn. This work provides a novel insight into the design of HEMs in catalytic application.

Background: Diabetic foot ulcers (DFUs) are among the most prevalent and dangerous complications of diabetes. Angiogenesis is pivotal for wound healing; however, its role in the chronic wound healing process in DFU requires further investigation. We aimed to investigate the pathogenic processes of angiogenesis in DFU from a molecular biology standpoint and to offer insightful information about DFU prevention and therapy. Methods: Differential gene and weighted gene co-expression network analyses (WGCNA) were employed to screen for genes related to DFU using the downloaded and collated GSES147890 datasets. With the goal of identifying hub genes, an interaction among proteins (PPI) network was constructed, and enrichment analysis was carried out. Utilizing a variety of machine learning techniques, including Boruta, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), we were able to determine which hub genes most strongly correspond to DFU. This allowed us to create an ideally suited DFU forecasting model that was validated via an external dataset. Finally, by merging 36 angiogenesis-related genes (ARGs) and machine learning models, we identified the genes involved in DFU-related angiogenesis. Results: By merging 260 genes located in the green module and 59 differentially expressed genes (DEGs), 35 candidate genes highly associated with DFU were found for more investigation. 35 candidate genes were enriched in epidermal growth factor receptor binding, nuclear division regulation, fluid shear stress, atherosclerosis, and negative regulation of chromosomal structure for the enrichment study. Fifteen hub genes were found with the aid of the CytoHubba plug. The LASSO method scored better in terms of prediction performance (GSE134341) (LASSO:0.89, SVM:0.65, Boruta:0.66) based on the validation of the external datasets. We identified thrombomodulin (THBD) as a key target gene that potentially regulates angiogenesis during DFU development. Based on the external validation dataset (GSE80178 and GSE29221), receiver operating characteristic (ROC) curves with higher efficiency were generated to confirm the potential of THBD as a biomarker of angiogenesis in DFU. Furthermore supporting this finding were the results of Western blot and real-time quantitative polymerase chain reaction (RT-qPCR), which showed decreased THBD expression in human umbilical vein endothelial cells (HUVECs) cultivated under high glucose. Conclusions: The findings implicate that THBD may influence DFU progression as a potential target for regulating angiogenesis, providing a valuable direction for future studies.

The prevention of diabetic foot ulcers (DFU) precedes treatment, in that early prevention significantly reduces the incidence of foot ulcers. The main objectives of this study were to examine the current prevalence of proactive foot ulcer examinations among diabetic patients and analyze influencing factors, in order to provide a scientific reference for the prevention of DFU in diabetic patients. The National Health and Nutrition Examination Survey (NHANES) 2011–2018 (n = 1278) data were utilized in this cross-sectional study. The dependent variable was whether patients underwent self-initiated foot ulcer inspections; risk factors that may lead to foot ulcers were included as independent variables. To explore the connection between the patient’s subjective motivation to inspect foot ulcers and risk variables, the weighted logistic regression model was further carried out. Among all risk factors, race, body mass index (BMI) and hypertension were statistically significant between whether patients were examined for foot ulcers or not. In the fully adjusted logistic regression model, only hypertension was positively correlated with diabetic patient-initiated examination for foot ulcers. This study suggests that there is still room for improvement in the knowledge and behavior of diabetic patients to be proactive in preventing DFU. Health care and community workers should conduct targeted training on diabetic foot prevention to reduce and prevent DFU by reinforcing knowledge to build positive attitudes and drive preventive behavior change.

ABSTRACTBalancing the potentially serious outcomes of asymptomatic brucellosis and “waiting” for treatment in clinical practice is an urgent issue. Therefore, we assessed the follow-up outcomes and epidemiological characteristics of asymptomatic brucellosis in the absence of treatment to provide evidence-based clinical clues. We searched eight databases in which 3610 studies from 1990 to 2021 were related to the follow-up outcomes of asymptomatic brucellosis. Thirteen studies, involving 107 cases, were finally included. Regarding the follow-up outcomes, we examined the presence or absence of symptoms and decreased serum agglutination test (SAT) titre. During the 0.5–18 months follow-up period, the pooled prevalence of appearing symptomatic was 15.4% (95% CI 2.1%–34.3%), cases that remained asymptomatic were 40.3% (95% CI 16.6%–65.8%), and decreased SAT titre was observed in 36.5% (95% CI 11.6%–66.1%). Subgroup analysis indicated that the pooled prevalence of appearing symptomatic with follow-up times of less than 6 months, 6–12 months, and 12–18 months was 11.5%, 26.4%, and 47.6%, respectively. The student subgroup had a higher prevalence of symptoms (46.6%) than the occupational and family populations. In conclusion, asymptomatic brucellosis has a high likelihood of appearing symptomatic and its severity may be underestimated. Active screening of occupational and family populations should be enhanced, and special attention should be paid to high-titre students for early intervention, if necessary. Additionally, future prospective, long-term, and large-sample follow-up studies are essential.

Objective This study was performed to evaluate the effect of a homemade autotransfusion pressure-control system on the regulation of negative pressure and to clarify the influence of different negative pressures on the recovered erythrocytes. Methods Fifty patients were randomly divided into five groups, and five different suction-generated negative pressures were applied. Before suction, 6 mL of blood was collected from the surgical field; after suction, 6 mL of blood was collected from the blood storage tank. The hemoglobin, hematocrit, mean corpuscular volume, newly generated standardized plasma free hemoglobin, and change in the hemolysis rate of erythrocytes before and after suction were compared. Additionally, the erythrocyte morphology was observed. Results The hemoglobin and hematocrit were significantly different before and after suction in all five groups. As the suction pressure increased, gradual increases were noted in the number of abnormal erythrocytes in the field of view, the newly generated standardized plasma free hemoglobin, and the change in the hemolysis rate. Conclusions The destruction rate of erythrocytes increased as the suction-generated negative pressure increased. When using a pressure-control system, a negative pressure of

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

Liver fibrosis and hepatocellular carcinoma (HCC) have been worldwide threats nowadays. Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage. In pathological liver, excessive H2O2 is generated and accumulated, which impacts the functionality of hepatocytes, Kupffer cells (KCs) and hepatic stellate cells (HSCs), leading to genesis of fibrosis and HCC. H2O2 accumulation is associated with overproduction of superoxide anion (O2•−) and abolished antioxidant enzyme systems. Plenty of therapeutics focused on H2O2 have shown satisfactory effects against liver fibrosis or HCC in different ways. This review summarized the reasons of liver H2O2 accumulation, and the role of H2O2 in genesis of liver fibrosis and HCC. Additionally, nanotherapeutics targeting H2O2 were summarized for further consideration of antifibrotic or antitumor therapy.

Abstract Cancer treatment by inducing tumor cell immunogenic cell death (ICD) is critical for tumor therapy. However, ICD activation by single pathway is often limited in practical application due to its low efficiency. In addition, the low pH and anoxic microenvironments in solid tumors greatly limit the effective activation of ICD. Herein, hollow manganese dioxide (H-MnO2) nanomaterials were selected to load both Mitoxantrone (MTZ) and Chlorin e6 (Ce6) due to its hollow structure and ability to release drugs in the acidic environments. Thus, the synergy of photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy can induce the process of immunogenic cell death, stimulate the maturation of dendritic cells (DCs), and activate the immune response to kill tumor cells dramatically. Efficient immunotherapeutic effects were obtained when MnO2-C/M-HA was given intravenously to 4T1 tumor-bearing BALB/c mice with 660 nm near-infrared laser irradiation. This study overcame the limitations of monotherapy and provided a multifunctional platform for tumor immunotherapy.

Enhanced anti-fibrotic effect on the liver is achieved by a multifunctional nanosystem combining CAT-like MnO2 and anti-fibrosis Saikosaponin b1

Can haze pollution effectively influence local government debt? This study uses data from 285 Chinese cities at the prefecture level or above from 2006 to 2019, and uses annual average sunny days as an instrumental variable to systematically analyze the impact of haze pollution on local government debt from both theoretical and empirical perspectives. The main conclusions of this study are: (1) there is a positive correlation between haze pollution and local government debt; (2) sub-sample analysis suggests that the impact of haze pollution on local government debt shows heterogeneous effects in different cities and at different times; and (3) the analysis of the relevant mechanism suggests that haze pollution can promote local government debt through industrial structure upgrading and green technology innovation. The research conclusions provide policy references for Chinese local governments to effectively respond to haze pollution.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19).MethodsA total of 420 confirmed COVID-19 patients were included in the study. According to the “Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)”, the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data.ResultsMale patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P

BackgroundThe treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis.MethodsWe searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes.ResultsThe meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter's test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results.ConclusionsIn the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.

Elucidating the effect of soil moisture on the adaptation of dominant plants in coastal wetlands is important for predicting the evolution of vegetation in the region. In this paper, Tamarix chinensis, a dominant species in the Yellow River Delta, was used as the object to study the changes of its growth and physiological parameters with increasing soil salinity under different moisture conditions (normal watering, persistent drought and persistent waterlogging). Different salt stress (2‰, 5‰, 8‰, 12‰, 16‰, and 20‰) using pot experiments was also used to reveal the mechanism of soil moisture on its salt tolerance. The results showed that the relative growth rate between 5‰-8‰ soil salinity was the largest, and growth was significantly inhibited above 20‰. Among different moisture conditions, the difference in relative growth rate under normal watering and persistent drought were nonsignificant, while both were significantly lower than those under persistent waterlogging. With increasing soil salinity, relative water content and total chlorophyll content significantly decreased, and cell membrane permeability (malondialdehyde), sodium ion, osmoregulatory substances (proline, soluble protein), and protective enzyme activity (SOD) significantly increased, while changes in non-structural carbohydrates (NSC) were not significant. Compared with normal watering and persistent waterlogging, persistent drought had the lowest leaf relative water content, total chlorophyll content, and sodium ions, and the highest cell membrane permeability, osmoregulatory substances and protective enzyme activity. With increasing treatment time, the relative leaf water content and total chlorophyll content significantly decreased, and cell membrane permeability, osmoregulatory substances and protective enzyme activity increased more significantly than normal watering and persistent waterlogging. NSC increased under normal watering and persistent waterlogging, while significantly decreased under persistent drought. Correlation analysis showed that the relationships between sodium ions, total chlorophyll content and malondialdehyde were various under different moisture conditions. Under persistent drough, malondialdehyde was significantly positively correlated with relative conductivity, superoxide dismutase, proline, soluble protein and soluble sugar. Total chlorophyll content was the key indicator reflecting the salt and waterlogging tolerance of T. chinensis under normal watering and persistent waterlogging, while cell membrane damage was under persistent drought. In summary, T. chinensis has strong salt and waterlogging tolerance, but persistent drought with salt stress can have serious impacts on its growth and survival.

BackgroundDiabetic osteoporosis exhibits heterogeneity at the molecular level. Ferroptosis, a controlled form of cell death brought on by a buildup of lipid peroxidation, contributes to the onset and development of several illnesses. The aim was to explore the molecular subtypes associated with ferroptosis in diabetic osteoporosis at the molecular level and to further elucidate the potential molecular mechanisms.MethodsIntegrating the CTD, GeneCards, FerrDb databases, and the microarray data of GSE35958, we identified ferroptosis-related genes (FRGs) associated with diabetic osteoporosis. We applied unsupervised cluster analysis to divide the 42 osteoporosis samples from the GSE56814 microarray data into different subclusters based on FRGs. Subsequently, FRGs associated with two ferroptosis subclusters were obtained by combining database genes, module-related genes of WGCNA, and differentially expressed genes (DEGs). Eventually, the key genes from FRGs associated with diabetic osteoporosis were identified using the least absolute shrinkage and selection operator (LASSO), Boruta, support vector machine recursive feature elimination (SVM ­ RFE), and extreme gradient boosting (XGBoost) machine learning algorithms. Based on ROC curves of external datasets (GSE56815), the model’s efficiency was examined.ResultsWe identified 15 differentially expressed FRGs associated with diabetic osteoporosis. In osteoporosis, two distinct molecular clusters related to ferroptosis were found. The expression results and GSVA analysis indicated that 15 FRGs exhibited significantly different biological functions and pathway activities in the two ferroptosis subclusters. Therefore, we further identified 17 FRGs associated with diabetic osteoporosis between the two subclusters. The results of the comprehensive analysis of 17 FRGs demonstrated that these genes were heterogeneous and had a specific interaction between the two subclusters. Ultimately, the prediction model had a strong foundation and excellent AUC values (0.84 for LASSO, 0.84 for SVM ­ RFE, 0.82 for Boruta, and 0.81 for XGBoost). IDH1 is a common gene to all four algorithms thus being identified as a key gene with a high AUC value (AUC = 0.698).ConclusionsAs a ferroptosis regulator, IDH1 is able to distinguish between distinct molecular subtypes of diabetic osteoporosis, which may offer fresh perspectives on the pathogenesis of the disease’s clinical symptoms and prognostic heterogeneity.

Abstract Background Superhydrophobic substrate modifications are an effective way to improve SERS sensitivity by concentrating analyte molecules into a small surface area. However, it is difficult to manipulate low-volume liquid droplets on superhydrophobic substrates. Results To overcome this limitation, we deposited a hydrophilic Ti3C2Tx film on a superhydrophobic ZnO nanorod array to create a SERS substrate with improved analyte affinity. Combined with its interfacial charge transfer properties, this enabled a rhodamine 6G detection limit of 10−11 M to be achieved. In addition, the new SERS substrate showed potential for detection of biological macromolecules, such as microRNA. Conclusion Combined with its facile preparation, the SERS activity of ZnO/Ti3C2Tx suggests it may provide an ultrasensitive environmental pollutant-monitoring and effective substrate for biological analyte detection. Graphical Abstract

Abstract Serious concerns have been raised about the negative effects of the COVID-19 pandemic on population psychological well-being. However, limited data exist on the long-term effects of the pandemic on incident psychiatric morbidities among individuals with varying exposure to the pandemic. Leveraging prospective data from the community-based UK Biobank cohort, we included 308,400 participants free of diagnosis of anxiety or depression, as well as 213,757 participants free of anxiolytics or antidepressants prescriptions, to explore the trends in incident diagnoses and drug prescriptions for anxiety and depression from 16 March 2020 to 31 August 2021, compared to the pre-pandemic period (i.e., 1 January 2017 to 31 December 2019) and across populations with different exposure statuses (i.e., not tested for COVID-19, tested negative and tested positive). The age- and sex-standardized incidence ratios (SIRs) were calculated by month which indicated an increase in incident diagnoses of anxiety or depression among individuals who were tested for COVID-19 (tested negative: SIR 3.05 [95% confidence interval 2.88–3.22]; tested positive: 2.03 [1.76–2.34]), especially during the first six months of the pandemic (i.e., March-September 2020). Similar increases were also observed for incident prescriptions of anxiolytics or antidepressants (tested negative: 1.56 [1.47–1.67]; tested positive: 1.41 [1.22–1.62]). In contrast, individuals not tested for COVID-19 had consistently lower incidence rates of both diagnoses of anxiety or depression (0.70 [0.67–0.72]) and prescriptions of respective psychotropic medications (0.70 [0.68–0.72]) during the pandemic period. These data suggest a distinct rise in health care needs for anxiety and depression among individuals tested for COVID-19, regardless of the test result, in contrast to a reduction in health care consumption for these disorders among individuals not tested for and, presumably, not directly exposed to the disease.

Abstract Chemoresistance remains a huge challenge for effective treatment of non-small cell lung cancer (NSCLC). Previous studies have shown Chinese herbal extracts possess great potential in ameliorating tumor chemoresistance, however, the efficacy is clinically limited mainly because of the poor tumor-targeting and in vivo stability. The construction of nano-delivery systems for herbal extracts has been shown to improve drug targeting, enhance therapeutic efficacy and reduce toxic and side effects. In this study, a folic acid (FA)-modified nano-herb micelle was developed for codelivery of pristimerin (PRI) and paclitaxel (PTX) to enhance chemosensitivity of NSCLC, in which PRI could synergistically enhance PTX-induced growth inhibition of A549 cancer cell. PTX was firstly grafted with the FA-linked polyethylene glycol (PEG) and then encapsulated with PRI to construct the PRI@FA-PEG-PTX (P@FPP) nano-micelles (NMs), which exhibited improved tumor-targeting and in vivo stability. This active-targeting P@FPP NMs displayed excellent tumor-targeting characteristics without obvious toxicity. Moreover, inhibition of tumor growth and metastasis induced by P@FPP NMs were significantly enhanced compared with the combined effects of the two drugs (PRI in combination of PTX), which associated with epithelial mesenchymal transition inhibition to some extent. Overall, this active-targeting NMs provides a versatile nano-herb strategy for improving tumor-targeting of Chinese herbal extracts, which may help in the promotion of enhancing chemosensitivity of NSCLC in clinical applications.

Abstract Transparent physical models of real rocks fabricated using three-dimensional (3D) printing technology are used in photoelastic experiments to quantify the evolution of the internal stress and deformation fields of rocks. Therefore, they are rendered as an emerging powerful technique to quantitatively reveal the intrinsic mechanisms of rock failure. The mechanical behavior of natural rocks exhibits a significant size effect; however, limited research has been conducted on whether transparent physical models observe similar size effects. In this study, to make the transparent printed models accurately demonstrate the mechanical behavior of natural rocks and reveal the internal mechanism of the size effect in rock mechanical behavior, the size effect in 3D printed models of fractured and porous rocks under uniaxial compressive loading was investigated. Transparent cylindrical models with different sizes that contained different fractured and porous structures were printed using the fracture and porous characteristics extracted from natural coal and sandstone. The variation in uniaxial compressive strength and elastic modulus of fractured and porous models for increasing model sizes were obtained through uniaxial compression experiments. Finally, the influence of internal discontinuous structural features, such as fractures and pores, on the size effect pertaining to the mechanical behavior of the model was analyzed and elaborated by comparing it with the mechanical properties of the continuous homogeneous model without fractures and pores. The findings provided support and reference to analyze the size effect of rock mechanical behavior and the effect of the internal discontinuous structure using 3D printed transparent models.

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO2-x) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

With the increasing aging population, nursing care providers have been facing a substantial risk of work-related musculoskeletal disorders (WMSDs). Visual-based pose estimation methods, like OpenPose, are commonly used for ergonomic posture risk assessment. However, these methods face difficulty when identifying overlapping and interactive nursing tasks, resulting in missing and misidentified skeletons. To address this, we propose a skeleton compensation method using improved spatial temporal graph convolutional networks (ST-GCN), which integrates kinematic chain and action features to assess skeleton integrity and compensate for it. The results verified the effectiveness of our approach in optimizing skeletal loss and misidentification in nursing care tasks, leading to improved accuracy in calculating both skeleton joint angles and REBA scores. Moreover, comparative analysis against other skeleton compensation methods demonstrated the superior performance of our approach, achieving an 87.34% REBA accuracy score. Collectively, our method might hold promising potential for optimizing the skeleton loss and misidentification in nursing care tasks.

Healthcare services and rehabilitation equipment have entered a phase of rapid development driven by user requirements. However, the development of corresponding design models for rehabilitation equipment is lacking. A general framework and development process are urgently needed for neurorehabilitation physiotherapy equipment. To address problems such as inadequate knowledge representation in the design process and difficulties in modeling the functional structure of the product, we combined a decomposition topology model of neurorehabilitation physiotherapy equipment with the modular design method. We proposed a general model for the design of neurorehabilitation physiotherapy equipment comprising the following modules: requirements (R), function (F), principle workspace (W), behavior (B), and structure (S), i.e., the RFWBS model. Using the neurorehabilitation robotic glove as an example for design practice, in terms of kinematics, the mechanism is analyzed by establishing a Lagrangian coordinate system for resolution. The mechanism has three degrees of freedom and can achieve the natural flexion and extension angles of each finger joint. In terms of dynamics, during the entire finger extension, the angular acceleration is almost zero, and the average angular velocity is approximately 30~50°/s. This indicates that the mechanism is suitable for wearable use, validating the scientific and effective nature of the RFWBS expanded model.

With accelerating urbanization, Mount Tai is increasingly at risk of homogenization with other scenic spots, losing its landscape aesthetic characteristics as ‘the Most Revered of the Five Sacred Mountains’, which poses a growing threat to the long-term sustainable development of Mount Tai. Accordingly, this study takes texts written by different social groups as the research material and analyses the aesthetic themes and spatial distribution of the elements in the texts to determine the aesthetic characteristics of the Mount Tai landscape from multiple perspectives and long time series. This study complements the research on the Mount Tai landscape, which focuses on specific research material and time. The results of the study can help to raise awareness of the complexity and multiple values of Mount Tai landscapes and have implications for research and practice of other heritage landscapes.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown cause, and the involvement of fibroblasts in its pathogenesis is well recognized. However, a comprehensive understanding of fibroblasts’ heterogeneity, their molecular characteristics, and their clinical relevance in IPF is lacking. In this study, we aimed to systematically classify fibroblast populations, uncover the molecular and biological features of fibroblast subtypes in fibrotic lung tissue, and establish an IPF-associated, fibroblast-related predictive model for IPF. Herein, a meticulous analysis of scRNA-seq data obtained from lung tissues of both normal and IPF patients was conducted to identify fibroblast subpopulations in fibrotic lung tissues. In addition, hdWGCNA was utilized to identify co-expressed gene modules associated with IPF-related fibroblasts. Furthermore, we explored the prognostic utility of signature genes for these IPF-related fibroblast subtypes using a machine learning-based approach. Two predominant fibroblast subpopulations, termed IPF-related fibroblasts, were identified in fibrotic lung tissues. Additionally, we identified co-expressed gene modules that are closely associated with IPF-fibroblasts by utilizing hdWGCNA. We identified gene signatures that hold promise as prognostic markers in IPF. Moreover, we constructed a predictive model specifically focused on IPF-fibroblasts which can be utilized to assess disease prognosis in IPF patients. These findings have the potential to improve disease prediction and facilitate targeted interventions for patients with IPF.

The Mott insulator provides an excellent foundation for exploring a wide range of strongly correlated physical phenomena, such as high-temperature superconductivity, quantum spin liquid, and colossal magnetoresistance. A Mott insulator with the simplest degree of freedom is an ideal and highly desirable system for studying the fundamental physics of Mottness. In this study, we have unambiguously identified such an anticipated Mott insulator in a van der Waals layered compound Nb_{3}Cl_{8}. In the high-temperature phase, where interlayer coupling is negligible, density functional theory calculations for the monolayer of Nb_{3}Cl_{8} suggest a half-filled flat band at the Fermi level, whereas angle-resolved photoemission spectroscopy experiments observe a large gap. This observation is perfectly reproduced by dynamical mean-field theory calculations considering strong electron correlations, indicating a correlation-driven Mott insulator state. Since this half-filled band derived from a single 2a_{1} orbital is isolated from all other bands, the monolayer of Nb_{3}Cl_{8} is an ideal realization of the celebrated single-band Hubbard model. Upon decreasing the temperature, the bulk system undergoes a phase transition, where structural changes significantly enhance the interlayer coupling. This results in a bonding-antibonding splitting in the Hubbard bands, while the Mott gap remains dominant. Our discovery provides a simple and seminal model system for investigating Mott physics and other emerging correlated states.

There is a high risk of musculoskeletal discomfort and injury due to the lack of professional guidance and training in caregiving postures. This study aimed to develop a risk assessment and visualization method by analyzing caregiving postures. Participants with (n = 8) and without (n = 10) caregiving experience were recruited to simulate patient transfer from bed to wheelchair. The Rapid Entire Body Assessment (REBA) method lacked sensitivity in distinguishing the experienced and inexperienced groups. We found that the visualization of the center of gravity (COG) trajectory could represent distinct posture differences between the two groups. Based on this finding, we considered a modified REBA method combining the COG trajectory, load-bearing time, and asymmetric load parameters, named the Caregiving-REBA (C-REBA) method. Our results demonstrated that C-REBA could effectively distinguish experienced and inexperienced caregivers, especially in caregiving task Stages 2–4. In conclusion, the present work explored adjusting to the parameters of the REBA method. The proposed C-REBA method could be easily imbedded into the Internet of Things (IoT) device to assess the caregiving posture for providing visual guidance and warning of the risk of discomfort or injury.

The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, an RNA-based adaptive immune system found in bacteria and archaea, has catalyzed the development and application of a new generation of gene editing tools. Numerous studies have shown that this system can precisely target a wide range of human genes, including those associated with diseases such as cancer. In cancer research, the intricate genetic mutations in tumors have promoted extensive utilization of the CRISPR/Cas9 system due to its efficient and accurate gene editing capabilities. This includes improvements in Chimeric Antigen Receptor (CAR)-T-cell therapy, the establishment of tumor models, and gene and drug target screening. Such progress has propelled the investigation of cancer molecular mechanisms and the advancement of precision medicine. However, the therapeutic potential of genome editing remains underexplored, and lingering challenges could elevate the risk of additional genetic mutations. Here, we elucidate the fundamental principles of CRISPR/Cas9 gene editing and its practical applications in tumor research. We also briefly discuss the primary challenges faced by CRISPR technology and existing solutions, intending to enhance the efficacy of this gene editing therapy and shed light on the underlying mechanisms of tumors.