Precisely Self-Cooperative Nanoassembly Enables Photothermal/Ferroptosis Synergistic Tumor Eradication.

Ferroptosis is identified as a potential target for anticancer therapy. However, most conventional ferroptosis inducers not only fail to trigger intracellular lipid peroxidation storm, but are also prone to cause ferroptosis-related toxicity through off-target destruction of intracellular antioxidant defense systems. Therefore, a potent and highly tumor-specific ferroptosis induction modality is desired. Herein, a self-cooperative nanomedicine for imaging-guided photothermal ferrotherapy, which is fabricated based on molecular nanoassembly (NA) of DiR (a photothermal probe) and ferrocene (Fc, a reactant of the Fenton reaction), is elaborately exploited. DiR-elicited hyperthermia induces both photothermal therapy (PTT) and a significant acceleration of the kinetics of the Fc-involved Fenton reaction, collaboratively causing a lipid peroxidation storm in tumor cells. In turn, plenty of lipid peroxides boost PTT through the downregulation of heat shock protein 90. As expected, such a self-cooperative NA demonstrates synergetic tumor eradication in the 4T1 breast tumor-bearing mice xenograft model. This study offers a novel nanotherapeutic paradigm for precise multimodal cancer therapy.

Association of Retinal Neurovascular Impairment with Disease Severity in Patients with Major Depressive Disorder: An Optical Coherence Tomography Angiography Study.

Background: Identifying the fundus objective biomarkers for the major depressive disorders (MDD) may help promote mental health. The aim of this study was to evaluate retinal neurovascular changes and further investigate their association with disease severity in MDD. Methods: This cross-sectional study conducted in the hospital enrolled patients with MDD and healthy controls.The retinal neurovascular parameters for all subjects, including vessel density (VD), thickness of ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL), and optic nerve head (ONH) eg are automatically calculated by the software in optical coherence tomography angiography (OCTA). The severity of MDD including depressive symptoms, anxiety, cognition, and insomnia was assessed by Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), and Insomnia Severity Index (ISI) respectively. Results: This study included 74 MDD patients (n=74 eyes) and 60 healthy controls (HCs) (n=60 eyes). MDD patients showed significantly decreased VD of superficial and deep capillary plexus, thickness of GCC and RNFL, and volume of ONH (all p<0.05) and increased vertical cup-to-disc ratio and global loss volume (GLV) (all p<0.05) compared to HCs. Positive associations were found between HAMD scores and cup area (r=0.30, p=0.035), cup volume (r=0.31, p=0.029), and disc area (r=0.33, p=0.020) as well as ISI scores and RNFL thickness (r=0.34, p=0.047). Conclusion: We found the retinal neurovascular impairment and its association with disease severity in MDD patients. OCTA showed promise as a potential complementary assessment tool for MDD.

Genomic basis determining root system architecture in maize.

KEY MESSAGE: A total of 389 and 344 QTLs were identified by GWAS and QTL mapping explaining accumulatively 32.2-65.0% and 23.7-63.4% of phenotypic variation for 14 shoot-borne root traits using more than 1300 individuals across multiple field trails. Efficient nutrient and water acquisition from soils depends on the root system architecture (RSA). However, the genetic determinants underlying RSA in maize remain largely unexplored. In this study, we conducted a comprehensive genetic analysis for 14 shoot-borne root traits using 513 inbred lines and 800 individuals from four recombinant inbred line (RIL) populations at the mature stage across multiple field trails. Our analysis revealed substantial phenotypic variation for these 14 root traits, with a total of 389 and 344 QTLs identified through genome-wide association analysis (GWAS) and linkage analysis, respectively. These QTLs collectively explained 32.2-65.0% and 23.7-63.4% of the trait variation within each population. Several a priori candidate genes involved in auxin and cytokinin signaling pathways, such as IAA26, ARF2, LBD37 and CKX3, were found to co-localize with these loci. In addition, a total of 69 transcription factors (TFs) from 27 TF families (MYB, NAC, bZIP, bHLH and WRKY) were found for shoot-borne root traits. A total of 19 genes including PIN3, LBD15, IAA32, IAA38 and ARR12 and 19 GWAS signals were overlapped with selective sweeps. Further, significant additive effects were found for root traits, and pyramiding the favorable alleles could enhance maize root development. These findings could contribute to understand the genetic basis of root development and evolution, and provided an important genetic resource for the genetic improvement of root traits in maize.

Global, regional, and national burden of blindness and vision loss attributable to high fasting plasma glucose from 1990 to 2019, and forecasts to 2030: A systematic analysis for the Global Burden of Disease Study 2019.

AIMS: To systematically clarify the spatiotemporal trends, and age-sex-specific blindness and vision loss (BVL) burden due to high fasting plasma glucose (HFPG) from 1990 to 2019, and project this burden over the next decade. MATERIALS AND METHODS: We obtained the number and rate of years lived with disability (YLDs) for the BVL burden attributable to HFPG by age, sex, socio-demographic index (SDI), and location between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 database. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of HFPG-attributable BVL burden. The Bayesian age-period-cohort model was used to predict the HFPG-attributable BVL burden. RESULTS: In 2019, the global number and age-standardized rate (ASR) for YLDs of BVL attributable to HFPG were 673.13 (95% UI: 159.52 to 1565.34) thousand and 8.44 (95% UI: 2.00 to 19.63) per 100,000 people, respectively. The highest burdens were found in Oceania, South Asia, and Southeast Asia, and the BVL burden due to HFPG was higher in the elderly and lower SDI regions. From 1990 to 2019, the global ASR of HFPG-attributable BVL gradually increased with AAPC (95% CI) being 0.80 (0.74 to 0.86). In addition, the HFPG-attributable BVL burden will slightly increase in the future decade. CONCLUSIONS: The HFPG remains the important cause of BVL worldwide, placing a substantial disease burden. From 1990 to 2019, the age-standardized burden of BVL due to HFPG increased, and will consistently increase in the future decade, particularly in the elderly and in regions with middle SDI or below.

Synthesis and Preliminary Evaluation of an ASGPr-Targeted Polycationic ß-Cyclodextrin Carrier for Nucleosides and Nucleotides.

Most antiviral and anticancer nucleosides are prodrugs that require stepwise phosphorylation to their triphosphate nucleotide form for biological activity. Monophosphorylation may be rate-limiting, and the nucleotides may be unstable and poorly internalized by target cells. Effective targeting and delivery systems for nucleoside drugs, including oligonucleotides used in molecular therapeutics, could augment their efficacy. The development of a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor (ASGPr) is now reported. In this work, the polycationic, polygalactosyl drug delivery carrier heptakis[6-amino-6-deoxy-2-O-(3-(1-thio-ß-D-galactopyranosyl)-propyl)]-ß-cyclodextrin hepta-acetate salt (GCyDAc), potentially a bifunctional carrier of (poly)nucleotides, was modeled by molecular docking in silico as an ASGPr-ligand, then synthesized for testing. The antivirals arabinosyl adenine (araA, vidarabine, an early generation antiviral nucleoside), arabinosyl adenine 5'-monophosphate (araAMP), and 12-mer-araAMP (p-araAMP) were selected for individual formulation with GCyDAc to develop this concept. Experimentally, beta cyclodextrin was decorated with seven protonated amino substituents on the primary face, and seven thiogalactose residues on its secondary face. AraA, araAMP, and p-araAMP were individually complexed with GCyDAc and complex formation for each drug was confirmed by differential scanning calorimetry (DSC). Finally, the free drugs and their GCyDAc complexes were evaluated for antiviral activity using ASGPr-expressing HepAD38 cells in cell culture. In this model, araA, araAMP, and p-araAMP showed relative antiviral potencies of 1.0, 1.1, and 1.2, respectively. In comparison, GCyDAc-complexes of araA, araAMP, and p-araAMP were 2.5, 1.3, and 1.2 times more effective than non-complexed araA in suppressing viral DNA production. The antiviral potencies of these complexes were minimally supportive of the hypothesis that ASGPr-targeted, CyD-based charge-association complexation of nucleosides and nucleotides could effectively enhance antiviral efficacy. GCyDAc was non-toxic to mammalian cells in cell culture, as determined using the MTS proliferation assay.

Linkage and association mapping in multi-parental populations reveal the genetic basis of carotenoid variation in maize kernels.

Carotenoids are indispensable to plants and critical components of the human diet. The carotenoid metabolic pathway is conserved across plant species, but our understanding of the genetic basis of carotenoid variation remains limited for the seeds of most cereal crops. To address this issue, we systematically performed linkage and association mapping for eight carotenoid traits using six recombinant inbred line (RIL) populations. Single linkage mapping (SLM) and joint linkage mapping (JLM) identified 77 unique additive QTLs and 104 pairs of epistatic QTLs. Among these QTLs, we identified 22 overlapping hotspots of additive and epistatic loci, highlighting the important contributions of some QTLs to carotenoid levels through additive or epistatic mechanisms. A genome-wide association study based on all RILs detected 244 candidate genes significantly associated with carotenoid traits, 23 of which were annotated as carotenoid pathway genes. Effect comparisons suggested that a small number of loci linked to pathway genes have substantial effects on carotenoid variation in our tested populations, but many loci not associated with pathway genes also make important contributions to carotenoid variation. We identified ZmPTOX as the causal gene for a QTL hotspot (Q10/JLM10/GWAS019); this gene encodes a putative plastid terminal oxidase that produces plastoquinone-9 used by two enzymes in the carotenoid pathway. Natural variants in the promoter and second exon of ZmPTOX were found to alter carotenoid levels. This comprehensive assessment of the genetic mechanisms underlying carotenoid variation establishes a foundation for rewiring carotenoid metabolism and accumulation for efficient carotenoid biofortification.

Integrated analyses reveal unexpected complex inversion and recombination in RH genes.

Phenotype D-- is associated with severe hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. It is typically caused by defective RHCE genes. In this study, we identified a D-- phenotype proband and verified RH phenotypes of other six family members. However, inconsistent results between the phenotypic analysis and Sanger sequencing revealed intact RHCE exons with no mutations in the D-- proband, but the protein was not expressed. Subsequent Oxford Nanopore Technologies whole-genome sequencing of the proband revealed an inversion with ambiguous breakpoints in the intron 2 and intron 7 and copy number variation loss in the RHCE gene region. Given that the RHCE gene is highly homologous to the RHD gene, we conducted a comprehensive analysis using Pacific Biosciences long-read target sequencing, Bionano optical genome mapping, and targeted next-generation sequencing. Our findings revealed that the proband had two novel recombinant RHCE haplotypes, RHCE*Ce(1-2)-D(3-10) and RHCE*Ce(1-2)-D(3-10)-Ce(10-8)-Ce(3-10), with clear-cut breakpoints identified. Furthermore, the RH haplotypes of the family members were identified and verified. In summary, we made a novel discovery of hereditary large inversion and recombination events occurring between the RHD and RHCE genes, leading to lack of RhCE expression. This highlights the advantages of using integrated genetic analyses and also provides new insights into RH genotyping.

The outcome of early screening and treatment of developmental dysplasia of the hip in infants and toddlers in the Northern Guizhou region.

This study is an observation of the early screening and treatment effect of infant developmental dysplasia of the hip (DDH) in an area in China. From January 2016 to December 2017, we selected infants and toddlers with high-risk factors for DDH, such as asymmetric gluteal folds, unequal length of lower limbs, and limited hip joint abduction, who visited the Department of Child Health Care and the Outpatient Clinic of Pediatric Orthopedics at the Affiliated Hospital of Zunyi Medical University. In total, 1485 cases were divided into age groups, examined using Graf ultrasound and X-ray, and the results were analyzed. Meanwhile, early interventions were actively adopted for cases with abnormalities during the screening. The detection rates of DDH were 24.0%, 2.8%, 9.3%, and 12.2% among those with 0 to 6 months, 7 to 12 months, 13 to 18 months, and 19 to 24 months of age, respectively. Early and individualized corrective conservative treatment was considered for children with abnormalities, and the cure rates were 87.0%, 65.7%, 41.0%, and 16.7% among those with 0 to 6 months, 7 to 12 months, 13 to 18 months, and 19 to 24 months of age, respectively. There was a statistically significant difference in the detection and cure rates of DDH in infants and toddlers of different ages (P < .01).

Global burden of all cause-specific injuries among children and adolescents from 1990 to 2019: a prospective cohort study.

BACKGROUND: To assess the burden and change in incidence, death, and disability-adjusted life years (DALYs) for all-cause-specific injuries among children and adolescents in 204 countries and territories between 1990 and 2019. MATERIALS AND METHODS: Data were extracted from the Global Burden of Disease, Injury, and Risk Factor Study 2019 (GBD 2019). Global, regional, and country-level age-standardized rate (per 100 000) of incidence (ASRI), mortality (ASRM), and DALYs (ASRD) with 95% uncertainty interval (95% UI) of injuries were estimated by age, sex, socio-demographic index (SDI), and all-cause-specific injuries from 1990 to 2019. RESULTS: Overall, the ASRI, ASRM, and ASRD of injury were 9006.18 (95% UI: 7459.74-10 918.04), 23.04 (20.00-26.50), and 2020.19 (1759.47-2318.64) among children and adolescents worldwide in 2019, respectively. All the above indicators showed a downward trend from 1990 to 2019. In level 2 cause of injury, both the global transport injury and unintentional injury declined during the study years, while self-harm and interpersonal violence-related injury showed an increasing trend. High SDI regions had higher ASRI of injuries, but low SDI regions had higher ASRM and ASRD of injuries globally in 2019. Males had a higher burden of injuries than those in females. The ASRI of injuries is higher in adolescents aged 15-19 years, whereas the mortality and DALYs rate are higher among children under 5 years old. Moreover, adolescents aged 15-19 years and individuals living in Central Asia, Middle East, and Africa had higher ASRI, ASRM, and ASRD of injuries owing to self-harm and interpersonal violence. Generally, falls and road traffic injuries are the leading cause of injury among the population aged 0-19 years worldwide, but self-harm, interpersonal violence, and conflict and terrorism are also leading types of injuries in some regions, particularly in Low-Income Countries and Middle-Income Countries. CONCLUSIONS: Injury remains a major global public health problem among children and adolescents, although its burden at the worldwide level showed a decreasing trend from 1990 to 2019. Of concern, the burden of injuries caused by transport injuries, and unintentional injuries has shown a downward trend in most countries, while the burden caused by self-harm and interpersonal violence has shown an upward trend in most countries. These findings suggest that more targeted and specific strategies to prevent the burden of injuries should be reoriented, and our study provides important findings for decision-makers and healthcare providers to reduce injury burden among children and adolescents.

Cytoophidia: a conserved yet promising mode of enzyme regulation in nucleotide metabolism.

Nucleotide biosynthesis encompasses both de novo and salvage synthesis pathways, each characterized by significant material and procedural distinctions. Despite these differences, cells with elevated nucleotide demands exhibit a preference for the more intricate de novo synthesis pathway, intricately linked to modes of enzyme regulation. In this study, we primarily scrutinize the biological importance of a conserved yet promising mode of enzyme regulation in nucleotide metabolism-cytoophidia. Cytoophidia, comprising cytidine triphosphate synthase or inosine monophosphate dehydrogenase, is explored across diverse biological models, including yeasts, Drosophila, mice, and human cancer cell lines. Additionally, we delineate potential biomedical applications of cytoophidia. As our understanding of cytoophidia deepens, the roles of enzyme compartmentalization and polymerization in various biochemical processes will unveil, promising profound impacts on both research and the treatment of metabolism-related diseases.

Spatiotemporal heterogeneity and long-term impact of meteorological, environmental, and socio-economic factors on scrub typhus in China from 2006 to 2018.

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.

Effect of fire needle combined with traditional Chinese medicine on psoriasis: A systematic review and meta-analysis.

BACKGROUND: The mechanism of action of fire acupuncture and Chinese medicine in psoriasis is unclear. In this paper, the efficacy of the 2 therapies was compared through a comprehensive analysis of their recurrence rates for clinical reference. METHODS: In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM data from the establishment of the databases to May 2023. The study proposed to use randomized controlled trial research methods, excluding published literature, unpublished literature, literature with incomplete or inadequate information, animal experiments, literature reviews and systematic studies. Data were processed using STATA 15.1 software. RESULTS: Our group previous study found that the clinical efficacy of the fire-acupuncture group was significantly improved compared to that of Chinese herbal medicine alone (RR = 1.20, 95% CI: 1.13-1.27). Also, there were significant reductions in Psoriasis Area and Severity Index (PASI) score (SMD = -1.04,95% CI: -1.48 to -0.60), area of skin damage (SMD = -0.40,95% CI: -0.75 to -0.04), and pruritus (SMD = -1.04,95% CI: -1.32 to -0.76). Our previous study found that Dermatology Life Quality Index (DLQI) was significantly lower in the fire acupuncture group compared to herbal medicine alone (SMD = -1.61,95% CI: -3.08 to -0.15). The combined analysis found that the recurrence rate was significantly lower in the fire-acupuncture group compared to herbal medicine alone (RR = 0.21,95% CI:0.07-0.60). CONCLUSION: Fire needle can improve the efficacy of TCM in the treatment of psoriasis, including the area, severity and itching of skin lesions, and reduce the recurrence rate, which is worthy of clinical promotion.

1,2-Dichloroethane induces testicular pyroptosis by activating piR-mmu-1019957/IRF7 pathway and the protective effects of melatonin.

1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.

Increased LL37 in psoriasis and other inflammatory disorders promotes LDL uptake and atherosclerosis.

Patients with chronic inflammatory disorders such as psoriasis have an increased risk of cardiovascular disease and elevated levels of LL37, a cathelicidin host defense peptide that has both antimicrobial and proinflammatory properties. To explore whether LL37 could contribute to the risk of heart disease, we examined its effects on lipoprotein metabolism and show that LL37 enhanced LDL uptake in macrophages through the LDL receptor (LDLR), scavenger receptor class B member 1 (SR-B1), and CD36. This interaction led to increased cytosolic cholesterol in macrophages and changes in expression of lipid metabolism genes consistent with increased cholesterol uptake. Structure-function analysis and synchrotron small-angle x-ray scattering showed structural determinants of the LL37-LDL complex that underlie its ability to bind its receptors and promote uptake. This function of LDL uptake is unique to cathelicidins from humans and some primates and was not observed with cathelicidins from mice or rabbits. Notably, Apoe-/- mice expressing LL37 developed larger atheroma plaques than did control mice, and a positive correlation between plasma LL37 and oxidized phospholipid on apolipoprotein B (OxPL-apoB) levels was observed in individuals with cardiovascular disease. These findings provide evidence that LDL uptake can be increased via interaction with LL37 and may explain the increased risk of cardiovascular disease associated with chronic inflammatory disorders.

The light and hypoxia induced gene ZmPORB1 determines tocopherol content in the maize kernel.

Tocopherol is an important lipid-soluble antioxidant beneficial for both human health and plant growth. Here, we fine mapped a major QTL-qVE1 affecting γ-tocopherol content in maize kernel, positionally cloned and confirmed the underlying gene ZmPORB1 (por1), as a protochlorophyllide oxidoreductase. A 13.7 kb insertion reduced the tocopherol and chlorophyll content, and the photosynthetic activity by repressing ZmPORB1 expression in embryos of NIL-K22, but did not affect the levels of the tocopherol precursors HGA (homogentisic acid) and PMP (phytyl monophosphate). Furthermore, ZmPORB1 is inducible by low oxygen and light, thereby involved in the hypoxia response in developing embryos. Concurrent with natural hypoxia in embryos, the redox state has been changed with NO increasing and H2O2 decreasing, which lowered γ-tocopherol content via scavenging reactive nitrogen species. In conclusion, we proposed that the lower light-harvesting chlorophyll content weakened embryo photosynthesis, leading to fewer oxygen supplies and consequently diverse hypoxic responses including an elevated γ-tocopherol consumption. Our findings shed light on the mechanism for fine-tuning endogenous oxygen concentration in the maize embryo through a novel feedback pathway involving the light and low oxygen regulation of ZmPORB1 expression and chlorophyll content.

Application of fractional carbon dioxide laser monotherapy in keloids: A meta-analysis.

BACKGROUND: There is no evidence-based guidance on the use of fractional CO2 laser in the excision of scars. AIM: To explore the effectiveness and safety of fractional CO2 laser in the treatment of keloids. METHODS: In this meta-analysis, we searched the PubMed, Embase, and Cochrane databases from inception to April 2023. We only included studies reporting fractional CO2 laser treatment of keloids. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. RESULTS: The pooled results showed that the Vancouver Scar Scale (VSS) parameters of height weighted mean difference (WMD) = -1.10, 95% confidence interval (CI): -1.46 to -0.74), pigmentation (WMD = -0.61, 95% CI: -1.00 to -0.21), and pliability (WMD = -0.90, 95% CI: -1.17 to -0.63) were significantly improved after fractional CO2 laser treatment of keloids. However, vascularity did not significantly change. Additionally, the total VSS was significantly improved after treatment (WMD = -4.01, 95% CI: -6.22 to -1.79). The Patient Scars Assessment Scale was significantly improved after treatment (WMD = -15.31, 95% CI: -18.31 to -12.31). Regarding safety, the incidences of hyperpigmentation, hypopigmentation, pain, telangiectasia, and atrophy were 5%, 0%, 11%, 2% (95% CI: 0%-6%), and 0% (95% CI: 0%-4%), respectively. CONCLUSIONS: Fractional CO2 laser is effective in the treatment of keloids and can effectively improve the height, pigmentation, and pliability of scars, and patients are satisfied with this treatment. Further studies should explore the role of combination therapy.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.

Genome-wide identification of the MADS-box gene family in Avena sativa and its role in photoperiod-insensitive oat.

Background: Traditional spring-summer sown oat is a typical long-day crop that cannot head under short-day conditions. The creation of photoperiod-insensitive oats overcomes this limitation. MADS-box genes are a class of transcription factors involved in plant flowering signal transduction regulation. Previous transcriptome studies have shown that MADS-box genes may be related to the oat photoperiod. Methods: Putative MADS-box genes were identified in the whole genome of oat. Bioinformatics methods were used to analyze their classification, conserved motifs, gene structure, evolution, chromosome localization, collinearity and cis-elements. Ten representative genes were further screened via qRT‒PCR analysis under short days. Results: In total, sixteen AsMADS genes were identified and grouped into nine subfamilies. The domains, conserved motifs and gene structures of all AsMADS genes were conserved. All members contained light-responsive elements. Using the photoperiod-insensitive oat MENGSIYAN4HAO (MSY4) and spring-summer sown oat HongQi2hao (HQ2) as materials, qRT‒PCR analysis was used to analyze the AsMADS gene at different panicle differentiation stages under short-day conditions. Compared with HQ2, AsMADS3, AsMADS8, AsMADS11, AsMADS13, and AsMADS16 were upregulated from the initial stage to the branch differentiation stage in MSY4, while AsMADS12 was downregulated. qRT‒PCR analysis was also performed on the whole panicle differentiation stages in MSY4 under short-day conditions, the result showed that the expression levels of AsMADS9 and AsMADS11 gradually decreased. Based on the subfamily to which these genes belong, the above results indicated that AsMADS genes, especially SVP, SQUA and Mα subfamily members, regulated panicle development in MSY4 by responding to short-days. This work provides a foundation for revealing the function of the AsMADS gene family in the oat photoperiod pathway.

High crosstalk suppression in InGaAs/InP single-photon avalanche diode arrays by carrier extraction structure.

Crosstalk has become an urgent issue for single-photon avalanche diode arrays. In previous work, trenches were introduced between pixels to block the crosstalk optical path in planar InGaAs/InP single-photon avalanche diode arrays, since the optical crosstalk was considered as the main crosstalk mechanism. However, the crosstalk suppression effect of this solution is not satisfactory. Here, we demonstrate a carrier extraction structure to efficiently reduce crosstalk by electrically guiding photogenerated crosstalk holes in the non-pixel region to the surface, since we find that the optical-electrical crosstalk is the dominant crosstalk mechanism. Experimental measurements show that a narrow carrier extraction structure makes a 91.52% (96.22%) crosstalk reduction between the nearest neighbor pixels in arrays with 100 (50) µm pixel pitch, and it does not cause any etching damage. These results reveal the primary source of crosstalk in InGaAs/InP single-photon avalanche diode arrays and provide a practical route to fabricate low-crosstalk, high-pixel-density arrays for use in high-resolution three-dimensional imaging and quantum technologies.