Stomatal response to VPD in C4 plants with different biochemical sub-pathways.

C4 NAD-malic enzyme (NAD-ME) species occurs in drier regions and exhibit different drought responses compared to C4 NADP-malic enzyme (NADP-ME) species. However, a physiological mechanism explaining the geographical discrepancies remains uncertain. This study examined gas exchange patterns that might explain different distributions observed between two subtypes of C4 photosynthesis. We measured the response of leaf gas exchange to vapour pressure deficit (VPD) and CO2 in plants from six distinct C4 clades having closely related NAD-ME and NADP-ME species using a Li-Cor 6400 gas exchange system. We found that NAD-ME species exhibited greater relative reductions in stomatal conductance with increases in VPD than NADP-ME species but observed no consistent subtype differences in C4 cycle activity as indicated by the initial slope of the A response to intercellular CO2 concentration. Based on these results, we hypothesise the greater response of gs to increasing VPD may enable NAD-ME plants to outperform NADP-ME plants in hot, dry environments where VPD is normally high.

Efficient AAV9 Purification Using a Single-Step AAV9 Magnetic Affinity Beads Isolation.

Adeno-associated viruses (AAVs) have emerged as promising tools for gene therapy due to their safety and efficacy in delivering therapeutic genes or gene editing sequences to various tissues and organs. AAV serotype 9 (AAV9), among AAV serotypes, stands out for its ability to efficiently target multiple tissues, thus holding significant potential for clinical applications. However, existing methods for purifying AAVs are cumbersome, expensive, and often yield inconsistent results. In this study, we explore a novel purification strategy utilizing Dynabeads™ CaptureSelect™ magnetic beads. The AAV9 magnetic beads capture AAV9 with high specificity and recovery between 70 and 90%, whereas the AAVX magnetic beads did not bind to the AAV9. Through continuous interaction with AAVs in solution, these beads offer enhanced clearance of genomic DNA and plasmids even in the absence of endonuclease. The beads could be regenerated at least eight times, and the used beads could be stored for up to six months and reused without a significant reduction in recovery. The potency of the AAV9-purified vectors in vivo was comparable to that of iodixanol purified vectors.

First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model.

The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4-5-week-old Laron dwarf mice (GHR-/-) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 × 1010 vector genome per mouse. Serum growth hormone (GH) levels decreased, and GH-responsive IGF1, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS) increased. There was a significant but limited increase in body weight and length, similar to the response to rhIGF1 treatment in LS patients. All the major organs increased in weight except the brain. Our study is the first to use gene therapy to treat GH-receptor deficiency. We propose that gene therapy with AAV-GHR may eventually be useful for the treatment of human LS.

Landslide Susceptibility Mapping with Integrated SBAS-InSAR Technique: A Case Study of Dongchuan District, Yunnan (China).

Landslide susceptibility maps (LSM) are often used by government departments to carry out land use management and planning, which supports decision makers in urban and infrastructure planning. The accuracy of conventional landslide susceptibility maps is often affected by classification errors. Consequently, they become less reliable, which makes it difficult to meet the needs of decision-makers. Therefore, it is proposed in this paper to reduce classification errors and improve LSM reliability by integrating the Small Baseline Subsets-Interferometric Synthetic Aperture Radar (SBAS-InSAR) technique and LSM. By using the logistic regression model (LR) and the support vector machine model (SVM), experiments were conducted to generate LSM in the Dongchuan district. It was classified into five classes: very high susceptibility, high susceptibility, medium susceptibility, low susceptibility, and very low susceptibility. Then, the surface deformation rate of the Dongchuan area was obtained through the ascending and descending orbit sentinel-1A data from January 2018 to January 2021. To correct the classification errors, the SBAS-InSAR technique was integrated into LSM under the optimal model by constructing the contingency matrix. Finally, the LSMs obtained before and after correction were compared. Moreover, the correction results were validated and analyzed by combining remote sensing images, InSAR deformation results, and field surveys. According to the research results, the susceptibility class of 66,094 classification error cells (59.48 km2) was significantly improved in the LSM after the integration of the SBAS-InSAR correction. The enhanced susceptibility classes and the spectral characteristics of remote sensing images are highly consistent with the trends of InSAR cumulative deformation and the results of field investigation. It is suggested that integrating SBAS-InSAR and LSM is effective in correcting classification errors and further improving the reliability of LSM for landslide prediction. The LSM obtained by using this method plays an important role in guiding local government departments on disaster prevention and mitigation, which is conducive to eliminating the risk of landslides.

Feature Analysis of Scanning Point Cloud of Structure and Research on Hole Repair Technology Considering Space-Ground Multi-Source 3D Data Acquisition.

As one of the best means of obtaining the geometry information of special shaped structures, point cloud data acquisition can be achieved by laser scanning or photogrammetry. However, there are some differences in the quantity, quality, and information type of point clouds obtained by different methods when collecting point clouds of the same structure, due to differences in sensor mechanisms and collection paths. Thus, this study aimed to combine the complementary advantages of multi-source point cloud data and provide the high-quality basic data required for structure measurement and modeling. Specifically, low-altitude photogrammetry technologies such as hand-held laser scanners (HLS), terrestrial laser scanners (TLS), and unmanned aerial systems (UAS) were adopted to collect point cloud data of the same special-shaped structure in different paths. The advantages and disadvantages of different point cloud acquisition methods of special-shaped structures were analyzed from the perspective of the point cloud acquisition mechanism of different sensors, point cloud data integrity, and single-point geometric characteristics of the point cloud. Additionally, a point cloud void repair technology based on the TLS point cloud was proposed according to the analysis results. Under the premise of unifying the spatial position relationship of the three point clouds, the M3C2 distance algorithm was performed to extract the point clouds with significant spatial position differences in the same area of the structure from the three point clouds. Meanwhile, the single-point geometric feature differences of the multi-source point cloud in the area with the same neighborhood radius was calculated. With the kernel density distribution of the feature difference, the feature points filtered from the HLS point cloud and the TLS point cloud were fused to enrich the number of feature points in the TLS point cloud. In addition, the TLS point cloud voids were located by raster projection, and the point clouds within the void range were extracted, or the closest points were retrieved from the other two heterologous point clouds, to repair the top surface and façade voids of the TLS point cloud. Finally, high-quality basic point cloud data of the special-shaped structure were generated.

Test and Analysis of Vegetation Coverage in Open-Pit Phosphate Mining Area around Dianchi Lake Using UAV-VDVI.

This work aimed to detect the vegetation coverage and evaluate the benefits of afforestation and ecological protection. Unmanned aerial vehicle (UAV) aerial survey was adopted to obtain the images of tailings area at Ma'anshan near the Dianchi Lake estuary, so as to construct a high-resolution Digital Orthophoto Map (DOM) and high-density Dense Image Matching (DIM) point cloud. Firstly, the optimal scale was selected for segmentation by considering the terrain. Secondly, the visible-band difference vegetation index (VDVI) of the classified vegetation information of the tail mining area was determined from the index gray histogram, ground class error analysis, and the qualitative and quantitative analysis of the bimodal index. Then, the vegetation information was extracted by combining the random forest (RF) classification algorithm. Finally, the extracted two-dimensional (2D) vegetation information was mapped to the three-dimensional (3D) point cloud, and the redundant data was eliminated. Fractional vegetation cover (FVC) was counted in the way of surface to point and human-machine combination. The experimental results showed that the vegetation information extracted from the 2D image was mapped to the 3D point cloud in the form of surface to point, and the redundant bare ground information was eliminated. The statistical FVC was 36.06%. The field survey suggested that the vegetation information in the turf dam area adjacent to the open phosphate deposit accumulation area research area was sparse. Relevant measures should be taken in the subsequent mining to avoid ecological damage caused by expanded phosphate mining. In general, applying UAV measurement technology and related 2D and 3D products to detect the vegetation coverage in an open phosphate mine area was of practical significance and unique technical advantages.

Roxarsone transformation and its impacts on soil enzyme activity in paddy soils: A new insight into water flooding effects.

The aromatic arsenical roxarsone (ROX) has been used as feed additive for decades worldwide. The past or present application of animal manure containing ROX in paddy fields results in arsenic (As) accumulation in rice grain. However, the degradation and transformation mechanisms of ROX in paddy soil which determine As bioavailability and uptake by rice are still unclear. The current study investigated the variation of As speciation and soil enzyme activities in ROX-treated soils under flooded and non-flooded conditions for six months. Our results showed that 70.2% of ROX persisted in non-flooded paddy soils after 180 d while ROX degraded completely within 7 d in flooded soils. The rapid degradation of ROX under flooded conditions owed to the enhanced biotic transformation that was caused by the low Eh and the predominant presence of Clostridium spp. and Bacillus spp. ROX was not only transformed to As(III) and As(V) in non-flooded soils but also to 3-amino-4-hydroxyphenylarsonic acid and methyl arsenicals in flooded soils. The degradation products significantly inhibited soil enzyme activities for 7-30 d, but the inhibition effects disappeared after 90 d due to the sorption of transformed As products to amorphous Fe oxides. This study provides new insights into the flooding effect on ROX fate in paddy fields, which is important for the management of animal waste and risk control on polluted sites.

Studies on Three-Dimensional (3D) Accuracy Optimization and Repeatability of UAV in Complex Pit-Rim Landforms As Assisted by Oblique Imaging and RTK Positioning.

Unmanned Aerial Vehicles (UAVs) are a novel technology for landform investigations, monitoring, as well as evolution analyses of long-term repeated observation. However, impacted by the sophisticated topographic environment, fluctuating terrain and incomplete field observations, significant differences have been found between 3D measurement accuracy and the Digital Surface Model (DSM). In this study, the DJI Phantom 4 RTK UAV was adopted to capture images of complex pit-rim landforms with significant elevation undulations. A repeated observation data acquisition scheme was proposed for a small amount of oblique-view imaging, while an ortho-view observation was conducted. Subsequently, the 3D scenes and DSMs were formed by employing Structure from Motion (SfM) and Multi-View Stereo (MVS) algorithms. Moreover, a comparison and 3D measurement accuracy analysis were conducted based on the internal and external precision by exploiting checkpoint and DSM of Difference (DoD) error analysis methods. As indicated by the results, the 3D scene plane for two imaging types could reach an accuracy of centimeters, whereas the elevation accuracy of the orthophoto dataset alone could only reach the decimeters (0.3049 m). However, only 6.30% of the total image number of oblique images was required to improve the elevation accuracy by one order of magnitude (0.0942 m). (2) An insignificant variation in internal accuracy was reported in oblique imaging-assisted datasets. In particular, SfM-MVS technology exhibited high reproducibility for repeated observations. By changing the number and position of oblique images, the external precision was able to increase effectively, the elevation error distribution was improved to become more concentrated and stable. Accordingly, a repeated observation method only including a few oblique images has been proposed and demonstrated in this study, which could optimize the elevation and improve the accuracy. The research results could provide practical and effective technology reference strategies for geomorphological surveys and repeated observation analyses in sophisticated mountain environments.

Periodontal disease and the risk of prostate cancer: a meta-analysis of cohort studies.

BACKGROUND: Periodontal disease is reportedly associated with the risk of various systemic diseases, including pancreatic and lung cancers. However, its association with prostate cancer remains inconclusive. Herein, we explored the association of periodontal disease with the risk of prostate cancer through a meta-analysis. MATERIALS AND METHODS: MEDLINE, Embase, Web of Sciences and Cochrane Library databases were searched for eligible publications up to April 2020. Multivariate adjusted risk estimates with corresponding 95% confidence intervals (CIs) were extracted and calculated using random- or fixed-effect models. RESULTS: Nine cohort studies involving 3.353 prostate cancer cases with 440.911 participants were identified and included in the meta-analysis. We found that periodontal disease significantly increased the risk of prostate cancer by 1.40-fold (hazard ratio [HR]=1.40, 95% CI: 1.16-1.70; P=0.001; I2=76.1%) compared with normal condition. Interestingly, the risk of developing prostate cancer was not significant in patients treated with periodontal therapy (HR=1.22, 95% CI: 0.86-1.73; P=0.272; I2=65.2%). The results of subgroup analyses were also consistent and significant when stratified by study design and follow-up period, whereas conflicting results were observed in periodontal disease ascertainment stratification. These findings were robust as indicated by sensitivity analyses. CONCLUSIONS: Periodontal disease was associated with the increased risk of prostate cancer, whereas no significant association was observed in patients treated with periodontal therapy. Hence, the awareness and importance for maintaining oral health should be improved, and the underlying mechanisms linking periodontal disease and prostate cancer should be fully explored in future research.

Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis.

OBJECTIVE: This study aims to design a novel semirigid ureterorenoscope with irrigation and vacuum suction system and a modified ureteral access sheath (UAS) named Sotn ureterorenoscope® (Sotn=ShuoTong Medical Company) to overcome the deficiencies of the current procedure and to improve the efficiency and safety of using Sotn ureterorenoscope® for treatment of upper urinary calculi. MATERIALS AND METHODS: Fifty-eight patients, comprising 31 males and 27 females, were evaluated. The medical records of 58 patients with upper urinary calculi treated with Sotn ureterorenoscope® from March 2015 to June 2017 were retrospectively reviewed at the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and one month after treatment. The secondary outcome was postoperative complication rate. RESULTS: The mean and SD of operative duration was 78.5 (30.4) min, and the mean and SD of stone size was 15.6 (5.6) mm. The primary overall SFR was 89.7% (52/58) and 100% at 1 month follow-up. Complication, which was Clavien I (minor fever managed by antipyretic therapy), was detected in 1.7% (1/58) of the patients. CONCLUSIONS: Sotn ureterorenoscope® is technically feasible, efficacious and safe for treatment of upper urinary calculi because of its advantages of high SFR and low complication rates.

Immunosuppression overcomes insulin- and vector-specific immune responses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice.

We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days. Euglycaemia was also restored in spontaneously diabetic NOD mice, although these mice required a 7-10-fold higher dose of vector to achieve similar efficacy as the C57BL/6 mice and the immunodeficient NODscid mice. We detected CD8+ T cell reactivity to insulin and mild inflammatory infiltration in the livers of gene therapy recipient NOD mice, neither of which were observed in the treated C57BL/6 mice. Efficacy of the gene therapy in NOD mice was partially improved by targeting the immune system with anti-CD4 antibody treatment, while transfer of NOD mouse AAV2/8-reactive serum to recipients prevented successful restoration of euglycaemia in AAV2/8-HLP-hINSco-treated NODscid mice. Our data indicate that both immune cells and antibodies form a barrier to successful restoration of euglycaemia in autoimmune diabetic recipient mice with insulin gene therapy, but that this barrier can be overcome by increasing the dose of vector and by suppressing immune responses.

Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.

BACKGROUND: Diabetes mellitus is caused by a partial or complete lack of insulin production in the body. We have previously shown that a single injection of an adeno-associated virus serotype 8 (AAV8) vector carrying a modified and codon optimized human insulin gene induced hepatic production of insulin and corrected streptozotocin (STZ)-induced diabetes in mice for more than 1 year. Insulin production was constitutive, analogous to long-acting insulin therapy. METHODS: We have developed a single AAV8 vector with a Tet-Off regulatable system as a safety mechanism to turn off insulin secretion should hypoglycaemia develop in vector-treated diabetic mice. We first transfected HepG2 cells or freshly isolated rat hepatocytes in vitro with the Tet-Off system (pAAV-Tetoffbidir -Alb-luc) regulating a luciferase reporter gene. We subsequently incorporated a furin-cleavable codon-optimised human proinsulin cDNA into pAAV-Tetoffbidir backbone to form the doxycycline inducible pAAV-Tetoffbidir -Alb-hINSco. RESULTS: Using STZ-induced diabetic mice, we were able to switch off insulin secretion repeatedly with doxycycline administration, and showed full restoration of insulin secretion on withdrawing doxycycline. CONCLUSIONS: The present study provides proof of concept that, under circumstances when inappropriate basal insulin secretion is a safety concern, insulin secretion from AAV8 gene therapy can be turned off reversibly with doxycycline.

Report: Cytotoxic activity of phytochemicals from the stem bark of Calophyllum castaneum.

Phytochemical investigation on the dichloromethane stem bark extract of Calophyllum castaneum resulted in the isolation of five compounds, namely isoblancoic acid (1), blancoic acid (2), euxanthone (3), friedelin (4) and friedelinol (5). All these compounds were isolated for the first time from this plant. Their chemical structures were elucidated based on the spectroscopic analyses. The cytotoxicity of compounds 1-5 was assessed on a panel of cancer cell lines including bone (Saos-2, mg63), colorectal (HT29, Caco-2, HCC2998, SW48, HCT116, KM12), liver (HepG2), lung (H1299, Calu-3), and brain (C6), using 5-fluorouracil as positive control. Pronounced antiproliferative activities were observed for compound 1 which exhibited a comparable activity with the positive control, against brain (C6) and colorectal (SW48, KM12, HCT116) cancer cell lines showing IC50 values in the range of 14 to 65µM. Meanwhile, compound 5 displayed a greater cytotoxic effect showing at least 2-fold more strongly than the positive control, against C6 brain cancer cells. The assay findings have unveiled the therapeutic value of phytochemicals from Calophyllum castaneum as anti-cancer agents.

National population-based data on the incidence, prevalence, and psychiatric comorbidity of eating disorders in Taiwanese adolescents and young adults.

OBJECTIVE: Nationwide data on eating disorders (EDs) among East Asian populations are scarce. This study aimed to estimate the prevalence, incidence, and psychiatric comorbidities of EDs in Taiwan. METHOD: Drawing from the National Health Research Institute database, we identified the study subjects aged 11-34 years who received an ED diagnosis during ambulatory visits or hospitalization from 2001 to 2012. We analyzed the subjects by age and gender. Diagnoses for comorbid psychiatric disorders were entered in the analysis only if they occurred within 1 year before or after the ED diagnosis date. Rates were age- and sex-adjusted to the average population within the study period. RESULTS: The estimated mean annual incidence was approximately 11.11 (95% CI 10.51-11.72) per 100,000 residents, and the 1 year prevalence was 20.87 (95% CI 20.05-21.70) per 100,000 residents, with evidence of female predominance (female/male ratio = 10.95, 95% CI = 8.97-13.36). Incidence and prevalence peaked at ages 20-24 in females and at ages 25-29 in males. Both rates nearly doubled within a decade. Specifically, the anorexia nervosa trend recently stabilized in females and decreased in males, while that for bulimia nervosa increased in both females and males. The most common comorbid diagnoses were anxiety (53%) and major depressive disorders (22%). DISCUSSION: The incidence and prevalence of EDs were lower in Taiwan than in Western countries. However, these rates were rapidly rising, notably in males. The majority of Taiwanese ED patients also received a diagnosis for various psychiatric comorbidities, a finding worthy of clinical attention.

Promoter optimisation of lentiviral vectors for efficient insulin gene expression in canine mesenchymal stromal cells: potential surrogate beta cells.

BACKGROUND: The lack of an ideal cell type that can be easily acquired, modified to produce insulin, and re-implanted has been a limitation for ex vivo insulin gene therapy. Canine diabetes is currently treated with human insulin and is a good model for human diabetes. Mesenchymal stromal cells (MSCs) are a promising candidate cell type for gene therapy. In the present study, we optimised insulin production using lentiviral transduced canine MSCs (cMSCs), aiming to evaluate their ability for use as surrogate beta cells. METHODS: Canine MSCs were derived from bone marrow and validated by measuring the expression of MSC lineage specific markers. Lentivirus vectors encoding the proinsulin gene (with or without a Kozak sequence) under the control of spleen focus forming virus, cytomegalovirus, elongation factor 1α and simian virus 40 promotors were generated and used to transduce primary cMSCs and a hepatocyte cell line. The insulin-producing capacity of transduced primary cMSCs was assessed by measuring the concentration of C-peptide produced. RESULTS: Primary cMSC could be readily expanded in culture and efficiently transduced using lentiviral vectors encoding proinsulin. Increasing the multiplicity of infection from 3 to 20 led to an increase in C-peptide secretion (from 1700 to 4000 pmol/l). The spleen focus forming virus promoter conferred the strongest transcriptional ability. CONCLUSIONS: The results of the present study suggest that optimised lentiviral transduction of the insulin gene into primary cMSCs renders these cells capable of secreting insulin over both the short- and long-term, in sufficient quantities in vitro to support their potential use in insulin gene therapy.

Deterioration of left ventricular systolic function in extended Pacing to Avoid Cardiac Enlargement (PACE) trial: the predictive value of early systolic dyssynchrony.

AIMS: Biventricular (BiV) pacing was superior to right ventricular apical (RVA) pacing at extended follow-up in the Pacing to Avoid Cardiac Enlargement (PACE) trial. Early pacing-induced systolic dyssynchrony (DYS) might be related to mid-term result. However, it remains unknown whether early pacing-induced DYS can predict long-term reduction of left ventricular (LV) systolic function. METHODS AND RESULTS: Patients with standard pacing indications and normal LV ejection fraction (LVEF) were randomized either to BiV (n = 89) or RVA (n = 88) pacing. Seventy-four patients in the RVA group and 72 in the BiV pacing group completed follow-up longer than 2 years. Serial echocardiography was performed with DYS assessed by tissue Doppler imaging, and the early pacing-induced DYS was defined as >33 ms by using standard deviation of the time to peak systolic velocity (Dyssynchrony Index) in a 12-segment model of LV at 1 month. There were 46 (32%) patients having early pacing-induced DYS that was more prevalent in the RVA pacing group than that in the BiV pacing group (50.7 vs. 12.3%, χ(2) = 25.1, P < 0.001) despite the similar DYS between the two groups at baseline (30 ± 13 vs. 26 ± 11 ms, P = 0.051). At a median follow-up of 4.8 years, patients developing early DYS had lower LVEF (53.2 ± 9.4 vs. 60.9 ± 8.0%, P < 0.001) and larger LV end-systolic volume (40.3 ± 23.7 vs. 29.3 ± 13.4 mL, P < 0.001) than those without DYS. Significant EF reduction (defined as ≥5%) occurred in 71.7% (33 in 46) of patients with DYS, but only in 30% (30 in 100) in those without DYS (χ(2) = 22.4, P < 0.001). Further analysis showed that both DYS at 1 month [odds ratio (OR): 3.113, P = 0.013] and RVA pacing (OR: 7.873, P < 0.001) independently predicted the deterioration of LV systolic function with pacing period of 4.8 years. CONCLUSION: Early pacing-induced DYS is a significant predictor of reduction of LV systolic function for long-term pacing, which could be prevented by BiV pacing at relatively long-period follow-up. CLINICAL TRIAL REGISTRATION: Centre for Clinical Trials number, CUHK_CCT00037 (URL: http://www.cct.cuhk.edu.hk/Registry/publictrialrecord.aspx?trialid=CUHK_CCT00037).

Human Wharton's jelly stem cells and its conditioned medium enhance healing of excisional and diabetic wounds.

Wound healing is a major problem in diabetic patients and current treatments have met with limited success. We evaluated the treatment of excisional and diabetic wounds using a stem cell isolated from the human umbilical cord Wharton's jelly (hWJSC) that shares unique properties with embryonic and adult mesenchymal stem cells. hWJSCs are non-controversial, available in abundance, hypo-immunogenic, non-tumorigenic, differentiate into keratinocytes, and secrete important molecules for tissue repair. When human skin fibroblasts (CCD) in conventional scratch-wound assays were exposed to hWJSC-conditioned medium (hWJSC-CM) the fibroblasts at the wound edges migrated and completely covered the spaces by day 2 compared to controls. The number of invaded cells, cell viability, total collagen, elastin, and fibronectin levels were significantly greater in the hWJSC-CM treatment arm compared to controls (P < 0.05). When a single application of green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs) or hWJSC-CM was administered to full-thickness murine excisional and diabetic wounds, healing rates were significantly greater compared to controls (P < 0.05). Wound biopsies collected at various time points showed the presence of green GFP-labeled hWJSCs, positive human keratinocyte markers (cytokeratin, involucrin, filaggrin) and expression of ICAM-1, TIMP-1, and VEGF-A. On histology, the GFP-hWJSCs and hWJSC-CM treated wounds showed reepithelialization, increased vascularity and cellular density and increased sebaceous gland and hair follicle numbers compared to controls. hWJSCs showed increased expression of several miRNAs associated with wound healing compared to CCDs. Our studies demonstrated that hWJSCs enhance healing of excisional and diabetic wounds via differentiation into keratinocytes and release of important molecules.

[Xiaojiang River Basin Ecological Environmental Quality Spatiotemporal Pattern and Evolutionary Trend Analysis Using GEE from 1990 to 2022].

Assessment and monitoring of the quality of the ecological environment in the area is a very important fundamental task in the development of ecological civilization in the Xiaojiang River Basin in Yunnan Province, which serves as a demonstration area for ecological restoration in the upper reaches of the Yangtze River. The Landsat remote sensing images from 1990, 1995, 2000, 2005, 2010, 2014, 2018, and 2022 were chosen, and the four indexes of greenness （NDMVI）, humidity （WET）, dryness （NDBSI）, and heat （LST） were extracted. The remote sensing ecological index （RSEI） was created using the principal component analysis method, then the spatial and temporal patterns and trends of ecological quality in the Xiaojiang River Basin between 1990 and 2022 were examined using the GEE platform, ArcGIS 10.7 platform, and Python platform, combining the analysis methods of geographic information mapping, coefficient of variation, Mann-Kendall trend test, Sen's slope estimation, and Hurst's index. The findings demonstrated that： ① the ecological quality of the study area had more obvious geographic differentiation spatially, and by 2022, the areas with excellent and good ecological quality grades were primarily distributed in the areas with better alpine vegetation cover, and those with poor ecological quality were primarily distributed in the areas of the mudslide ravines with relatively low terrain. On a time scale, the study area's RSEI index increased from 0.41 in 1990 to 0.55 in 2022, with a fluctuating overall trend of ecological quality improvement and an average increase of 0.048（10 a） -1； this progress was directly related to a number of ecological construction initiatives that have been energetically carried out, such as converting farms to forests, preventing mudslides, saving soil and water, managing heavy metal contamination, etc. ② The RSEI was more appropriate for the evaluation of ecological quality in alpine ravine areas because, in comparison to the NDVI index, the NDVMI adopted in this study was more sensitive to vegetation information in topographic undulation areas, especially in shaded areas, and could more accurately and quantitatively describe the vegetation information. ③ The RSEI in the Xiaojiang River Basin had a mean coefficient of variation of 0.202. Overall, its volatility was low, and its high volatility was mostly concentrated in the mudslide gully area along both sides of the Xiaojiang River fracture zone, where the surface was made up of bare rocks and sediment that was easily impacted by the changing of the seasons, the climate, and human activity. ④ The quality of the ecological environment in the region was significantly improving, with the rising area reaching 85.72% of the total area and the declining area accounting for approximately 10.15% of the total area. The future trend of change will be dominated by ongoing improvement and future degradation, accounting for 44.75% and 39.97%, respectively. It is important to pay close attention to areas that could potentially degrade. The findings of this study can serve as a theoretical foundation for additional ecological environmental conservation, management, and sustainable development in the Xiaojiang River Basin.

Wireless sequential dual light delivery for programmed PDT in vivo.

Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

The safety and efficacy of Sotn ureteroscopy for renal and upper ureteral calculi: a prospective multicenter randomized controlled trial.

BACKGROUND: Sotn ureteroscopy is a new lithotripsy procedure developed on the basis of ureteroscopy and includes a rigid ureteral access sheath, standard mirror, lithotripsy mirror, and Sotn perfusion aspirator. Thus, we performed a prospective multicenter randomized controlled trial comparing the safety and efficacy of Sotn ureteroscopy in the treatment of renal and upper ureteral calculi. METHODS: In this study, 224 patients with renal and upper ureteral calculi were randomly divided equally into study and control groups from March 2018 to March 2022. All the patients were approved by the hospital ethics committee (proof number: ZF-2018-164-01 and ZF-2018-165-01) of the Second Affiliate Hospital of Guangzhou University of Chinese Medicine in China. The primary outcome was stone-free rate (SFR) assessed by computed tomography on the 1st day and month after treatment and operation duration. The secondary outcome was postoperative complication rate. RESULTS: In total, for upper ureteral calculi, the SFR of 1 day after operation of the Sotn ureteroscopy group was significantly higher than the rigid ureteroscopy group (83.6% vs. 60%, P=0.006). Moreover, operative time (33.7±1.80 vs. 52.9±2.73 min, P<0.005) of the Sotn ureteroscopy group was significantly lower than the rigid ureteroscopy group. Additionally, the SFR of 1 day after operation and operative time for the study group (Sotn ureteroscopy combined with flexible ureteroscopy) and the control group (flexible ureteroscopy alone) were 63.2% and 36.8% (P=0.005), 65.6±4.06 and 80.3±4.91 (P=0.023), respectively. However, there were no significant differences in the SFR of 1 month after operation, success rate of ureteral access sheath placement, and postoperative complications between the two groups (P>0.05). In subgroups with stone diameters ≥1.5 cm and stone CT values ≥1000 Hounsfield units, Sotn ureteroscopy showed more advantages in terms of the SFR of 1 day after operation. Importantly, complications such as ureteral injury, sepsis, fever, and severe hematuria were not statistically different between the two groups (P>0.05). CONCLUSIONS: For renal and upper ureteral calculi, Sotn ureteroscopy has the advantage of a higher SFR of 1 day after the operation and a shorter operative time, suggesting that the Sotn ureteroscopy may have further potential applications in clinics.