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Since the beginning of the 21st century, vegetation greening in China has continuously increased and ranks among the top globally, especially in the western and northern regions of the country. This study analyzed the characteristics of the greening rates of different vegetation types in China's arid and semi-arid regions in the northwest, using satellite-derived Normalized Difference Vegetation Index (NDVI) data from 2002 to 2021. Furthermore, the study explored the response of greening rates to climate change and its temporal effect. The study found that in the past two decades, the vegetation greening rates in the southeastern region of China's arid and semi-arid areas are higher than that in the northwest. Vegetation change in the arid and semi-arid regions of China exhibits significant spatial heterogeneity in response to climate change. The vegetation greening rates in the southeast of the study area increases with precipitation, while in the northwest, it is promoted by daytime temperature and day-night temperature difference. The greening rates of cultivated vegetation, grassland, and meadow thicket is mainly affected by precipitation, while the greening rates of alpine grassland is mainly affected by day-night temperature difference. In addition, the response of vegetation greening rates to climate in China's arid and semi-arid regions has significant time lag and cumulative effects. Climate changes before the growing season (February to May) can also affect vegetation greening rates during the growing season (June to September). The cumulative climate changes over four months have a greater impact on vegetation greening rate than those over two months. Our study quantified the contribution of climate change to the greening rates of different vegetation types, which can provide references for predicting the dynamic changes of vegetation under future climate change.

Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was reported to contain an “inhibitor cocktail”, including phospholipase A2 inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges on S. annularis using venoms from Deinagkistrodon acutus, Agkistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLIα, PLIβ, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. annularis (LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of “natural immunity” in snakes, namely, the “antivenom”, which consists of an inhibitor proteome or cocktail.

The sloping seabed affects the bearing capacity and failure mechanism of soil, which may compromise the stability and safety of offshore structures such as jack-up platforms. This paper employs a coupled model combining the material point method and finite element method (MPM-FEM) to analyze the impact of sloping seabeds on the three-dimensional soil-spudcan interaction. The MPM-FEM model implements the B¯ approach to solve the challenge of volumetric locking due to the incompressibility constraints imposed by yield criterion. It is validated against the centrifuge results. The effects of sloping seabeds on penetration resistance, soil flow pattern, lateral response, stress distribution, and failure mechanism are discussed. The soil mainly undergoes overall failure when the ratio of penetration depth to spudcan diameter (i.e. DP/D) is between 0 and 0.25. As the slope angle increases, the soil on the side of lower slope is expelled further, resulting in an asymmetric stress distribution and a larger horizontal sliding force of soil. When DP/D increases to 0.75, the soil transitions to localized plastic flow failure, and the range of soil flow affected by the spudcan penetration decreases. The results show that, when the slope angle increases, the lateral displacement and stress distribution on the lower slope of a sloping seabed is significantly larger than that of a horizontal seabed, impacting the spudcan and surrounding soil behavior. The study suggests that the seabed slope significantly affects the range of soil flow and failure at shallow penetration, indicating that the slope angle should be taken into account in the design and installation of offshore jack-up rigs, particularly in areas with sloping seabeds.

Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p

The cast-in-place (CIP) pile is a type of deep foundation that has been widely used in various soils. However, the performance of CIP pile in dynamically compacted (DC) soil-rock mixtures has been rarely investigated. This study presents a field investigation on the performance of CIP piles in DC treated soil-rock mixtures. First, a 30-meter-thick soil-rock mixture layer on site was improved using DC (maximum energy level =10,000 kN·m) on grouting area and non-grouting area. Second, two groups of six CIP piles with a diameter of 1.2 m and a length of 34 m were constructed. After that, static pile load tests (SPLT) were carried out to evaluate the performance of CIP piles. The testing results suggest that the compressive bearing capacity of CIP pile in grouting area is identical to that installed in non-grouting area. The pile displacement in grouting area, however, was reduced over 40% under an applied load of 12,000 kN compared to non-grouting case. The DC treatment mobilized the shaft resistance in upper part of test piles (0 ∼ 10 m). The applied load shared by shaft resistance mobilized at depth of 0 ∼ 10 m is beyond 77% regardless of grouting, and the smaller the applied load, the higher the shared ratio. It indicated that the DC can significantly eliminate collapsibility within the main influence depth from water injection test. The grouting can eliminate the potential collapsibility and negative frictional resistance of pile side, which is especially beneficial in reducing pile displacement, improving the strength of thick soil-rock mixtures, and increasing bearing capacity of the CIP piles.

Chinese herbs have been used to treat small-cell lung cancer (SCLC) due to their low toxicity and significant efficacy. This study focused on oridonin, a natural compound extracted from Rabdosia rubescens, and aimed to investigate its potential antitumor activity on SCLC and to evaluate the synergistic effect of combining oridonin with other small molecules. In this study, oridonin exhibited a dual effect. At lower concentrations, it suppressed the cell viability of SCLC cells (H1688 and H446). At high concentrations, oridonin induced SCLC cell apoptosis, damaged HBE cells in vitro and compromised the function of the liver and heart in vivo. The lower concentration of oridonin induced autophagy by enhancing the expression of p62 and the LC3B-II/LC3B-I ratio. This phenomenon might be associated with the activation of the protein kinase RNA-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/growth arrest and DNA damage-inducible gene 153 (CHOP/GAD153) pathway. Therefore, the combined effect of oridonin with GSK2606414 or 3- methyladenine increased apoptosis in SCLC cells and reduced tumor growth. A similar phenomenon was observed after oridonin was combined with p62 or CHOP RNA interference treatment. Simultaneously, the combination of oridonin and GSK2606414 exhibited therapeutic efficacy without manifesting adverse effects. Our findings suggest that oridonin at lower concentrations can induce autophagy by activating the PERK/eIF2α/CHOP signaling pathway. The inhibition of the PERK/eIF2α/CHOP pathway could enhance oridonin therapeutic responses by triggering apoptosis. The novel therapeutic approach of combining oridonin with a PERK inhibitor is promising as a strategy for the treatment of SCLC.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Background: The cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, is predominantly produced by the choroid plexus of the ventricle. Although CSF-derived extracellular vesicles (CSF-EVs) may be utilized as diagnostic and prognostic indicators for illnesses of the central nervous system (CNS), it is uncertain if CSF-EVs may have an impact on neurological function after spinal cord injury (SCI). Methods: Here, we isolated EVs using ultracentrifugation after extracting CSF from Bama miniature pigs. We then combined CSF-EVs with hydrogel and put it on the spinal cord's surface. To determine if CSF-EVs had an impact on mice's neurofunctional recovery, behavioral evaluations were employed. Both in vitro and in vivo, the effect of CSF-EVs on angiogenesis was assessed. We investigated whether CSF-EVs stimulated the PI3K/AKT pathway to alter angiogenesis using the PI3K inhibitor LY294002. Results: CSF-EVs were successfully isolated and identified by transmission electron microscope (TEM), nano-tracking analysis (NTA), and western blot. CSF-EVs could be ingested by vascular endothelial cells as proved by in vivo imaging and immunofluorescence. We demonstrated that CSF-EVs derived from pigs with SCI (SCI-EVs) showed a better effect on promoting vascular regeneration as compared to CSF-EVs isolated from pigs receiving laminectomy (Sham-EVs). Behavioral assessments demonstrated that SCI-EVs could dramatically enhance motor and sensory function in mice with SCI. Western blot analysis suggested that SCI-EVs promote angiogenesis by activating PI3K/AKT signaling pathway, and the pro-angiogenetic effect of SCI-EVs was attenuated by the application of the LY294002 (PI3K inhibitor). Conclusion: Our study revealed that CSF-EVs could enhance vascular regeneration by activating the PI3K/AKT pathway, hence improving motor function recovery after SCI, which may offer potential novel therapeutic options for acute SCI. The translational potential of this article: This study demonstrated the promotion of vascular regeneration and neurological function of CSF-derived exosomes, which may provide a potential therapeutic approach for the treatment of spinal cord injury.

Dynamic compaction (DC) is an efficient ground treatment technique that has been widely used for different soil types, however, the investigation on performance of high energy level DC for soil-rock mixture backfills is rare so far. This study presents a field investigation of the effectiveness of DC with a maximum energy level of 10,000-kN·m on soil-rock mixtures in southwestern China. Field tests, including surface wave test (SWT), super heavy dynamic penetration test (SH-DPT), and plate load test (PLT) were conducted to evaluate the effectiveness of DC under different conditions. The effectiveness and improvement depth were discussed based on SWT and SH-DPT. The results showed that the ground bearing capacity increased significantly after DC treatment both under non-soaking and soaking conditions. For the testing site with a fill thickness of 10 m, the allowable ground bearing capacity exceeded 300 kPa after DC treatment. The deformation modulus was measured to be 15 MPa. However, the impact of DC on the site with a fill thickness of 30 m is limited, and additional ground improvement measures are required for design.

Summary: Background: With the growing demand for breast screening in public health services and clinical care, ultrasound departments in China are facing tremendous challenges. Methods: A cross-sectional nationwide survey was conducted in 5,460 departments providing ultrasound diagnoses in mainland China from 2020 to 2021. The survey included general information about the ultrasound department, the characteristics of sonologists, the use of Breast Imaging Reporting and Data System (BI-RADS) templates, and the diagnostic accuracy rate of breast cancer ultrasound. Findings: There were on average 2.25 sonologists per 10,000 patients in mainland China per year. The average utilization rate of BI-RADS in Chinese hospitals was 87.02%. The GDP per capita of the province (P = 0.008), whether the hospital was specialized (P = 0.002) or a Tier 3 facility (P < 0.001), the percentage of doctors with master's and doctoral degrees (P < 0.001) and doctors ≤35 years (P = 0.005) were significantly and independently associated with the utilization rate of BI-RADS. The average diagnostic accuracy rate of breast cancer ultrasound in Chinese hospitals was 73.64%, and we observed significant positive associations between GDP per capita (P = 0.02), BI-RADS utilization rate (P = 0.019), and breast cancer ultrasound diagnostic accuracy. Interpretation: The utilization of BI-RADS templates effectively improved the diagnostic accuracy of ultrasound. Moreover, the survey summarized the current situation of departments and sonologists providing breast ultrasound diagnosis in mainland China, which helped monitor the development of the discipline and provide information for administrators to meet the growing demand. Funding: This work was supported by Natural Science Foundation of Beijing (7202156) and Foundation of ihecc (2019-C-0646-2).

Breast cancer has become the most common malignant tumor worldwide. However, the survival rate of breast cancer patients in China is 8% lower compared to that in European and American countries. Insufficient screening coverage and low rate of early detection are key problems. Therefore, it is imperative to develop a set of guidelines for breast cancer screening, early diagnosis, and treatment strategies suitable for Chinese women. The National Health Commission, the National Cancer Center, and the National Cancer Quality Control Center collectively organized a committee of specialists with multidisciplinary backgrounds in breast surgery, oncology, radiotherapy, diagnostic imaging, ultrasound, pathology, epidemiology, and health economics. The committee collectively published ''China Breast Cancer Screening, Early Diagnosis and Treatment Specification'', in which the committee outlined a set of strategies of breast cancer screening, early diagnosis, and treatment suitable for China's national conditions. The strategies were formulated based on clinical experience in breast cancer prevention and treatment, characteristics of breast cancer patients in China, and socioeconomic conditions. The purpose of this article is to provide an interpretation of the above guidelines as a reference for breast cancer screening.

Multiple objective assessments have been used to assess the activity of keloids to compare different therapeutic regimens and facilitate the best individual treatment choice for patients, but none of them are standardized. A multimodal photoacoustic/ultrasonic (PA/US) imaging system, including photoacoustic imaging, elastography, ultra-micro-angiography, and conventional US technologies (gray scale US, color Doppler US, and power Doppler US), was applied to evaluate keloids by a radiologist. Growing stages were defined by patients, and Vancouver Scar Scale (VSS) was assessed by a plastic surgeon. A comprehensive model based on multimodal ultrasound parameters (poor-echo pattern, high vascular density, decreased elasticity, and low SO2 within the keloid) and VSS might be a potential indicator of active keloids, comparing with VSS alone. The multimodal PA/US imaging system could be a promising technique for keloids assessment.

By providing complementary functional information, photoacoustic (PA) breast imaging based on the handheld ultrasound (US) probe has demonstrated promising potential for breast cancer diagnosis. However, the quantitative PA imaging primarily relies on the knowledge of the optical fluence distribution in the three-dimensional (3D) heterogeneous breast tissue. Previous studies based on the handheld system generally provided two-dimensional (2D) B-scan results, which contains limited anatomical information of the tissue and the lesion. This study proposed a method to perform 3D modeling of the photon transportation for dual-modality PA/US system based on the local 3D breast anatomical information by scanning US probe. Then the calculated optical fluence distribution can be used for PA imaging. Our phantom and clinical pilot study results demonstrated that this method has potential to improve the accuracy of the quantitative PA breast imaging, and it can also be used in other clinical implementations.

Wetlands have multiple functions such as biodiversity protection, hydrological regime reduction, pollution sediment filtration, and tourism service etc., though wetland areas have been shrunken and fragmented largely recently, especially where nearby cities. A great application significance can be offered by the application of stormwater resources to wetland landscape restoration, which gives help to deal with the challenge of global precipitation fluctuation, and to build a sustainable and harmonious society between human and nature. In this study, the Priority Index for Wetland Restoration model (PIWR model) and the Stormwater Resources Richness Index model (SRRI model) were established based on 1 km grid unit by taking a typical county scale in northern China as the study area. On this basis, three optimal areas with the PIWR values over 0.43 were evaluated as the targeted areas to receive local stormwater resources, while two areas with the richest stormwater resources of SRRI values over 0.65 were selected as the best water supply areas for the wetland restoration activity. Finally, the optimal and scientific approach was presented based on the proposed accessibility method for utilizing the potential stormwater resources to the planed restore wetland sites at the regional scale. The evaluation framework was supported by proximity analysis and spatial coupling analysis of hydrology and geomorphology based on the suggested multiple ecohydrological indicator matrix. This study presented a useful method framework to help wetland restoration by reducing regional flood disaster with a linkage between an ecological matrix and a hydrological matrix at the regional scale, which can be applied for those regions with a quick loss of wetlands due to the ecological water shortage, while challenged by more and more flooding disasters caused by the coming global climate change.