The joint impact of PM2.5 constituents on the risk of cerebrovascular diseases hospitalization: A large community-based cohort study.

Air pollution poses significant health risks to urban areas, with limited focus on the chronic association of PM2.5 and its constituents on cerebrovascular diseases (CERs), especially regarding the joint associations. This study explores the individual and joint associations between PM2.5 constituents and CER hospitalization risks through a cohort analysis of 36,271 adults in the Pearl River Delta, South China, from 2015 to 2020. Cox proportional hazards regression and quantile-based g-computation models were used to quantify the individual and joint associations of annual mean concentrations of PM2.5 constituents with hospitalization for CERs. 1151 participants were hospitalized due to CERs during the five-year follow-up period. Joint associations analyses identified that one quartile increase in co-exposure may result in hazard ratios of 1.530 (1.441-1.623), 1.840 (1.710-1.980), and 1.609 (1.491-1.737) for CERs, total, and ischemic stroke hospitalization, respectively. The adverse effect was primarily driven by organic matter and chlorine. Men, those with a history of tobacco or alcohol use or with low residential greenness, were more susceptible to CERs hospitalization following PM2.5 constituents co-exposure. Upcoming strategies should focus on monitoring and regulating PM2.5 constituents, encouraging healthy lifestyles, and enhancing urban greenery.

Mesoporous Graphene Oxide Nanocomposite Effective for Combined Chemo/Photo Therapy Against Non-Small Cell Lung Cancer.

Introduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC. Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model. Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment. Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC.

Comparative Analysis of Chloroplast Genomes in Cephaleuros and Its Related Genus (Trentepohlia): Insights into Adaptive Evolution.

Cephaleuros species are well-known as plant pathogens that cause red rust or algae spot diseases in many economically cultivated plants that grow in shady and humid environments. Despite their prevalence, the adaptive evolution of these pathogens remains poorly understood. We sequenced and characterized three Cephaleuros (Cephaleuros lagerheimii, Cephaleuros diffusus, and Cephaleuros virescens) chloroplast genomes, and compared them with seven previously reported chloroplast genomes. The chloroplast sequences of C. lagerheimii, C. diffusus, and C. virescens were 480,613 bp, 383,846 bp, and 472,444 bp in length, respectively. These chloroplast genomes encoded 94 genes, including 27 tRNA genes, 3 rRNA genes, and 64 protein-coding genes. Comparative analysis uncovered that the variation in genome size was principally due to the length of intergenic spacer sequences, followed by introns. Furthermore, several highly variable regions (trnY-GTA, trnL-TAG, petA, psbT, trnD-GTC, trnL-TAA, ccsA, petG, psaA, psaB, rps11, rps2, and rps14) were identified. Codon bias analysis revealed that the codon usage pattern of Cephaleuros is predominantly shaped by natural selection. Additionally, six chloroplast protein-coding genes (atpF, chlN, psaA, psaB, psbA, and rbcL) were determined to be under positive selection, suggesting they may play a vital roles in the adaptation of Cephaleuros to low-light intensity habitats.

Whole-tumoral metabolic heterogeneity in 18F-FDG PET/CT is a novel prognostic marker for neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB. METHODS: We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC). RESULTS: During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS. CONCLUSION: WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

CircZNF609 sponges miR-135b to up-regulate SEMA3A expression to alleviate ox-LDL-induced atherosclerosis.

The initiation and progression of atherosclerotic plaque caused by abnormal lipid metabolism is one of the main causes of atherosclerosis (AS). Lipid droplet accumulation has become a novel research pointcut for AS treatment in recent years. In AS patients, miR-135b level was up-regulated relative to the normal cases, which showed negative correlations with the levels of Semaphorin 3A (SEMA3A) and circZNF609, separately. The U937-derived macrophages were cultured with ox-LDL to establish AS models in vitro. After that, the lipid accumulation, inflammation, mitochondrial dysfunction and cell death were evaluated by ORO, ELISA, RT-qPCR, western blot, JC-1 and FCM assays respectively. Transfection of the circZNF609 expression vector notably declined lipid accumulation, attenuated inflammation, reduced mitochondrial dysfunction and inhibited cell death in ox-LDL-stimulated cells. The direct binding of miR-135b to circZNF609 in vitro was confirmed using RIP assay, and SEMA3A expression was up-regulated by circZNF609 overexpression. After manipulating the endogenous expressions of circZNF609, miR-135b and SEMA3A, the above damages in ox-LDL-stimulated cells were rescued by inhibition of miR-135b expression and overexpression of circZNF609 or SEMA3A. Besides, the AS mice model was built to demonstrate the excessive lipid accumulation, increasing inflammation and cell death in AS pathogenesis according to the results of HE staining, ELISA and IHC assays, while these damages were reversed after overexpression of circZNF609 or SEMA3A. In AS models, overexpressed circZNF609 prevents the AS progression through depleting miR-135b expression and subsequent up-regulation of SEMA3A expression to overwhelm lipid accumulation, mitochondrial dysfunction and cell death.

GateView: A Multi-Omics Platform for Gene Feature Analysis of Virus Receptors within Human Normal Tissues and Tumors.

Viruses are obligate intracellular parasites that rely on cell surface receptor molecules to complete the first step of invading host cells. The experimental method for virus receptor screening is time-consuming, and receptor molecules have been identified for less than half of known viruses. This study collected known human viruses and their receptor molecules. Through bioinformatics analysis, common characteristics of virus receptor molecules (including sequence, expression, mutation, etc.) were obtained to study why these membrane proteins are more likely to become virus receptors. An in-depth analysis of the cataloged virus receptors revealed several noteworthy findings. Compared to other membrane proteins, human virus receptors generally exhibited higher expression levels and lower sequence conservation. These receptors were found in multiple tissues, with certain tissues and cell types displaying significantly higher expression levels. While most receptor molecules showed noticeable age-related variations in expression across different tissues, only a limited number of them exhibited gender-related differences in specific tissues. Interestingly, in contrast to normal tissues, virus receptors showed significant dysregulation in various types of tumors, particularly those associated with dsRNA and retrovirus receptors. Finally, GateView, a multi-omics platform, was established to analyze the gene features of virus receptors in human normal tissues and tumors. Serving as a valuable resource, it enables the exploration of common patterns among virus receptors and the investigation of virus tropism across different tissues, population preferences, virus pathogenicity, and oncolytic virus mechanisms.

Experimental test and mechanism analysis of soil crust erosion resistance of rammed earth Great Wall in rainy season.

Rammed earth is a kind of cleaning material, widely used in all kinds of buildings in the world. The Great Wall of ancient China is a typical world cultural site built from rammed earth. The rammed earth Great Wall of Shanhaiguan is close to Bohai Bay, which has suffered from long-term erosion by rain, causing a series of problems such as soil loss, collapse and gully flushing. The protection materials of the rammed earth site have always puzzled scholars. However, during the rainy season, it was found that some of the walls at Xiaowan Gouge and Nantuzhuang Gouge in the Shanhaiguan Great Wall had unwashed traces, the soil surface of the walls was intact, and the anti-erosion ability of the walls was significantly higher than that of other places. In order to explore the reasons for its strong anti-erosion ability in the natural state of rammed earth wall, guide the protection of rammed earth Great Wall, and carry out different experimental tests to explore its anti-erosion reasons and internal mechanisms. Firstly, the characteristics of rammed soil were understood through the composition test of rammed soil, and the indoor and outdoor erosion test was carried out to determine that the anti-erosion reason was the protection of gray-green soil crust. The property and composition of soil crust were determined through the immersion test and genome sequencing. Finally, the protection mechanism of soil crust was analyzed by scanning electron microscopy.

Controllable Pyridine N-Oxidation-Nucleophilic Dechlorination Process for Enhanced Dechlorination of Chloropyridines: The Cooperation of HCO4- and HO2.

Dechlorination of chloropyridines can eliminate their detrimental environmental effects. However, traditional dechlorination technology cannot efficiently break the C-Cl bond of chloropyridines, which is restricted by the uncontrollable nonselective species. Hence, we propose the carbonate species-activated hydrogen peroxide (carbonate species/H2O2) process wherein the selective oxidant (peroxymonocarbonate ion, HCO4-) and selective reductant (hydroperoxide anion, HO2-) controllably coexist by manipulation of reaction pH. Taking 2-chloropyridine (Cl-Py) as an example, HCO4- first induces Cl-Py into pyridine N-oxidation intermediates, which then suffer from the nucleophilic dechlorination by HO2-. The obtained dechlorination efficiencies in the carbonate species/H2O2 process (32.5-84.5%) based on the cooperation of HCO4- and HO2- are significantly higher than those in the HO2--mediated sodium hydroxide/hydrogen peroxide process (0-43.8%). Theoretical calculations confirm that pyridine N-oxidation of Cl-Py can effectively lower the energy barrier of the dechlorination process. Moreover, the carbonate species/H2O2 process exhibits superior anti-interference performance and low electric energy consumption. Furthermore, Cl-Py is completely detoxified via the carbonate species/H2O2 process. More importantly, the carbonate species/H2O2 process is applicable for efficient dehalogenation of halogenated pyridines and pyrazines. This work offers a simple and useful strategy to enhance the dehalogenation efficiency of halogenated organics and sheds new insights into the application of the carbonate species/H2O2 process in practical environmental remediation.

Selective anchoring of Pt NPs on covalent triazine-based frameworks via in situ derived bridging ligands for boosting photocatalytic hydrogen evolution.

The efficient and stable production of hydrogen (H2) through Pt-containing photocatalysts remains a great challenge. Herein, we develop an effective strategy to selectively and uniformly anchor Pt NPs (∼1.2 nm) on a covalent triazine-based framework photocatalyst via in situ derived bridging ligands. Compared to Pt/CTF-1, the obtained Pt/AT-CTF-1 exhibits a considerable photocatalytic H2 evolution rate of 562.9 µmol g-1 h-1 under visible light irradiation. Additionally, the strong interaction between the Pt NPs and in situ derived bridging ligands provides remarkable stability to Pt/AT-CTF-1. Experimental investigations and photo/chemical characterization reveal the synergy of the in situ derived bridging ligands in Pt/AT-CTF-1, which can selectively anchor the Pt NPs with homogeneous sizes and efficiently improve the transmission of charge carriers. This work provides a new perspective toward stabilizing ultrasmall nanoclusters and facilitating electron transfer in photocatalytic H2 evolution materials.

RMBase v3.0: decode the landscape, mechanisms and functions of RNA modifications.

Although over 170 chemical modifications have been identified, their prevalence, mechanism and function remain largely unknown. To enable integrated analysis of diverse RNA modification profiles, we have developed RMBase v3.0 (http://bioinformaticsscience.cn/rmbase/), a comprehensive platform consisting of eight modules. These modules facilitate the exploration of transcriptome-wide landscape, biogenesis, interactome and functions of RNA modifications. By mining thousands of epitranscriptome datasets with novel pipelines, the 'RNA Modifications' module reveals the map of 73 RNA modifications of 62 species. the 'Genes' module allows to retrieve RNA modification profiles and clusters by gene and transcript. The 'Mechanisms' module explores 23 382 enzyme-catalyzed or snoRNA-guided modified sites to elucidate their biogenesis mechanisms. The 'Co-localization' module systematically formulates potential correlations between 14 histone modifications and 6 RNA modifications in various cell-lines. The 'RMP' module investigates the differential expression profiles of 146 RNA-modifying proteins (RMPs) in 18 types of cancers. The 'Interactome' integrates the interactional relationships between 73 RNA modifications with RBP binding events, miRNA targets and SNPs. The 'Motif' illuminates the enriched motifs for 11 types of RNA modifications identified from epitranscriptome datasets. The 'Tools' introduces a novel web-based 'modGeneTool' for annotating modifications. Overall, RMBase v3.0 provides various resources and tools for studying RNA modifications.

ZmELF6-ZmPRR37 module regulates maize flowering and salt response.

The control of flowering time in maize is crucial for reproductive success and yield, and it can be influenced by environmental stresses. Using the approaches of Ac/Ds transposon and transposable element amplicon sequencing techniques, we identified a Ds insertion mutant in the ZmPRR37 gene. The Ds insertion showed a significant correlation with days to anthesis. Further research indicated that ZmPRR37-CR knockout mutants exhibited early flowering, whereas ZmPRR37-overexpression lines displayed delayed flowering compared to WT under long-day (LD) conditions. We demonstrated that ZmPRR37 repressed the expression of ZmNF-YC2 and ZmNF-YA3 to delay flowering. Association analysis revealed a significant correlation between flowering time and a SNP2071-C/T located upstream of ZmPRR37. The SNP2071-C/T impacted the binding capacity of ZmELF6 to the promoter of ZmPRR37. ZmELF6 also acted as a flowering suppressor in maize under LD conditions. Notably, our study unveiled that ZmPRR37 can enhance salt stress tolerance in maize by directly regulating the expression of ABA-responsive gene ZmDhn1. ZmDhn1 negatively regulated maize salt stress resistance. In summary, our findings proposed a novel pathway for regulating photoperiodic flowering and responding to salt stress based on ZmPRR37 in maize, providing novel insights into the integration of abiotic stress signals into floral pathways.

Multi-disciplinary cooperation for the micro-elimination of hepatitis C in China: a hospital-based experience.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the main causes of liver cancer and imposes an enormous social and economic burden. The blood-borne virus screening policy for preventing iatrogenic infections renders hospitals important for identifying individuals infected with hepatitis C. Therefore, we aimed to investigate the establishment of a multi-disciplinary cooperation model in medical institutions to leverage the screening results of patients with hepatitis C. Our objective is to ensure that patients receive timely and effective diagnosis and treatment, thereby enabling the elimination of hepatitis C by 2030. METHOD: A multi-disciplinary cooperation model was established in October 2021. This retrospective study was based on the establishment of antibody-positive and HCV RNA-positive patient databases. A Chi-square test was used to compare the HCV RNA confirmation rate in anti-HCV-positive patients, as well as the hepatitis C diagnosis rate and treatment rate in RNA-positive patients before and after the multi-disciplinary cooperation. A multivariable logistic regression was used to analyse the factors affecting the treatment of patients with hepatitis C. In addition, we examined changes in the level of hepatitis C knowledge among medical staff. RESULTS: After the implementation of the multi-disciplinary cooperation model, the RNA confirmation rate of hepatitis C antibody-positive patients increased from 36.426% to 88.737%, the diagnostic accuracy rate of RNA-positive patients increased from 67.456% to 98.113%, and the treatment rate of patients with hepatitis C increased from 12.426% to 58.491%. Significant improvements were observed among the clinicians regarding their ability to understand the characteristics of hepatitis C (93.711% vs. 58.861%), identify people at high risk (94.340% vs. 53.797%), manage patients with hepatitis C after diagnosis (88.679% vs. 67.089%), and effectively treat hepatitis C (84.277% vs. 51.899%). Multi-disciplinary cooperation in medical institutions was the most important factor for patients to undergo HCV treatment (odds ratio: 0.024, 95% confidence interval: 0.007-0.074). CONCLUSIONS: This study showed that the use of a multi-disciplinary cooperation model to utilise the results of HCV antibody screening fully in patients through further tracking, referral, and treatment may facilitate the detection and treatment of patients with hepatitis C and accelerate the elimination of HCV in China.

Dermoscopy for the Diagnosis of Creeping Hair Caused by Ingrowing Hair: A Case Report.

Creeping hair is a rare condition characterized by creeping eruption with a black line at the advancing end, mimicking cutaneous larva migrans. The condition is also referred to as cutaneous pili migrans, migrating hair, and embedded hair. A total of 52 cases have been reported since 1957 and most cases were published in English. Herein, we report a case in which creeping hair occurred in the iliac region and review the literature from 1957 to February 2021. A 35-year-old Chinese female presented with a black moving linear eruption that had migrated from the lower abdomen to the iliac region without causing any symptoms during a 3-year period. Cutaneous examination showed a 6.5-cm-long black linear lesion beneath the skin that was revealed to be a hair shaft. After removal of the hair, the eruption diminished and no recurrence occurred in 3 months of follow-up. The creeping hair that had migrated with its lower end forward was confirmed by observation under dematoscopy and light microscopy. A review of the literature revealed that creeping hair occurs most frequently in young and middle-aged patients and the reported cases are mainly from Asia. The top locations involve the foot. The causative hair includes head hair, beard, pubic hair, body hair, and one case of dog hair. A close-up examination and dermoscopic inspection are helpful for the diagnosis of creeping hair.

Changes in nitrogen metabolism of phosphorus-starved bloom-forming cyanobacterium Microcystis aeruginosa: Implications for nutrient management.

The surplus of nitrogen plays a key role in the maintenance of cyanobacterial bloom when phosphorus has already been limited. However, the interplay between high nitrogen and low phosphorus conditions is not fully understood. Nitrogen metabolism is critical for the metabolism of cyanobacteria. Transcriptomic analysis in the present study suggested that nitrogen metabolism and ribosome biogenesis were the two most significantly changed pathways in long-term phosphorus-starved bloom-forming cyanobacteria Microcystis aeruginosa FACHB-905. Notably, the primary glutamine synthetase/glutamate synthase cycle, crucial for nitrogen metabolism, was significantly downregulated. Concurrently, nitrogen uptake showed a marked decrease due to reduced expression of nitrogen source transporters. The content of intracellular nitrogen reservoir phycocyanin also showed a drastic decrease upon phosphorus starvation. Our study demonstrated that long-term phosphorus-starved cells also suffered from nitrogen deficiency because of the reduction in nitrogen assimilation, which might be limited by the reduced ribosome biogenesis and the shortage of adenosine triphosphate. External nitrogen supply will not change the transcriptions of nitrogen metabolism-related genes significantly like that under phosphorus-rich conditions, but still help to maintain the survival of phosphorus-starved cells. The study deepens our understanding about the survival strategies of Microcystis cells under phosphorus starvation and the mutual dependence between nitrogen and phosphorus, which would provide valuable information for nutrient management in the eutrophicated water body.

Phase-Engineering of Layered Nickel Hydroxide for Synthesizing High-Quality NiOx Nanocrystals for Efficient Inverted Flexible Perovskite Solar Cells.

Nickel oxide (NiOx) nanocrystals have been widely used in inverted (p-i-n) flexible perovskite solar cells (fPSCs) due to their remarkable advantages of low cost and outstanding stability. However, anion and cation impurities such as NO3- widely exist in the NiOx nanocrystals obtained from calcinated nickel hydroxide (Ni(OH)2). The impurities impair the photovoltaic performance of fPSCs. In this work, we report a facile but effective way to reduce the impurities within the NiOx nanocrystals by regulating the Ni(OH)2 crystal phase. We add different alkalis, such as organic ammonium hydroxide and alkali metal hydroxides, to nickel nitrate solutions to precipitate layered Ni(OH)2 with different crystalline phase compositions (α and ß mixtures). Especially, Ni(OH)2 with a high ß-phase content (such as from KOH) has a narrower crystal plane spacing, resulting in fewer residual impurity ions. Thus, the NiOx nanocrystals, by calcinating the Ni(OH)x with excess ß phase from KOH, show improved performance in inverted fPSCs. A champion power conversion efficiency (PCE) of 20.42% has been achieved, which is among the state-of-art inverted fPSCs based on the NiOx hole transport material. Moreover, the reduced impurities are beneficial for enhancing the fPSCs' stability. This work provides an essential but facile strategy for developing high-performance inverted fPSCs.

Integrative profiling of extrachromosomal circular DNA in placenta and maternal plasma provides insights into the biology of fetal growth restriction and reveals potential biomarkers.

Introduction: Fetal growth restriction (FGR) is a placenta-mediated pregnancy complication that predisposes fetuses to perinatal complications. Maternal plasma cell-free DNA harbors DNA originating from placental trophoblasts, which is promising for the prenatal diagnosis and prediction of pregnancy complications. Extrachromosomal circular DNA (eccDNA) is emerging as an ideal biomarker and target for several diseases. Methods: We utilized eccDNA sequencing and bioinformatic pipeline to investigate the characteristics and associations of eccDNA in placenta and maternal plasma, the role of placental eccDNA in the pathogenesis of FGR, and potential plasma eccDNA biomarkers of FGR. Results: Using our bioinformatics pipelines, we identified multi-chromosomal-fragment and single-fragment eccDNA in placenta, but almost exclusively single-fragment eccDNA in maternal plasma. Relative to that in plasma, eccDNA in placenta was larger and substantially more abundant in exons, untranslated regions, promoters, repetitive elements [short interspersed nuclear elements (SINEs)/Alu, SINEs/mammalian-wide interspersed repeats, long terminal repeats/endogenous retrovirus-like elements, and single recognition particle RNA], and transcription factor binding motifs. Placental multi-chromosomal-fragment eccDNA was enriched in confident enhancer regions predicted to pertain to genes in apoptosis, energy, cell growth, and autophagy pathways. Placental eccDNA-associated genes whose abundance differed between the FGR and control groups were associated with immunity-related gene ontology (GO) terms. The combined analysis of plasma and placental eccDNA-associated genes in the FGR and control groups led to the identification of potential biomarkers that were assigned to the GO terms of the epigenetic regulation of gene expression and nutrient-related processes, respectively. Conclusion: Together, our results highlight links between placenta functions and multi-chromosomal-fragment and single-fragment eccDNA. The integrative analysis of placental and plasma eccDNA confirmed the potential of these molecules as disease-specific biomarkers of FGR.

3D printing titanium grid scaffold facilitates osteogenesis in mandibular segmental defects.

Bone fusion of defect broken ends is the basis of the functional reconstruction of critical maxillofacial segmental bone defects. However, the currently available treatments do not easily achieve this goal. Therefore, this study aimed to fabricate 3D-printing titanium grid scaffolds, which possess sufficient pores and basic biomechanical strength to facilitate osteogenesis in order to accomplish bone fusion in mandibular segmental bone defects. The clinical trial was approved and supervised by the Medical Ethics Committee of the Chinese PLA General Hospital on March 28th, 2019 (Beijing, China. approval No. S2019-065-01), and registered in the clinical trials registry platform (registration number: ChiCTR2300072209). Titanium grid scaffolds were manufactured using selective laser melting and implanted in 20 beagle dogs with mandibular segmental defects. Half of the animals were treated with autologous bone chips and bone substances incorporated into the scaffolds; no additional filling was used for the rest of the animals. After 18 months of observation, radiological scanning and histological analysis in canine models revealed that the pores of regenerated bone were filled with titanium grid scaffolds and bone broken ends were integrated. Furthermore, three patients were treated with similar titanium grid scaffold implants in mandibular segmental defects; no mechanical complications were observed, and similar bone regeneration was observed in the reconstructed patients' mandibles in the clinic. These results demonstrated that 3D-printing titanium grid scaffolds with sufficient pores and basic biomechanical strength could facilitate bone regeneration in large-segment mandibular bone defects.

SAPM: Self-Adaptive Parallel Manipulator with Pose and Force Adjustment for Robotic Ultrasonography.

Robotic ultrasonography potentially acts as an essential aid to medical diagnosis. To overcome the limitations in robotic ultrasonography, in this paper, we proposed a novel self-adaptive parallel manipulator (SAPM) that can automatically adjust the ultrasound (US) probe pose to adapt to various contours of scanned areas, provide approximate constant operating forces/torques, achieve mechanical measurement, and cushion undesired produced forces. A novel parallel adjustment mechanism is proposed to attain automatic pose adjustment with 3 degrees of freedom (DOFs). This mechanism enables the US probe to adapt to different scanned areas and to perform the scanning with approximate constant forces and torques. Besides, we present a mechanical measurement and safety protection method that can be integrated into the SAPM and used as operation status monitoring and early warning during scanning procedures by capturing operating forces and torques. Experiments were carried out to calibrate the measurement and buffer units and evaluate the performance of the SAPM. Experimental results show the ability of the SAPM to provide 3-DoFs motion and operating force/torque measurement and automatically adjust the US probe pose to capture US images of equally good quality compared to a manual sonographer scan. Moreover, it has characteristics similar to soft robots that could significantly improve operation safety, and could be extended to some other engineering or medical applications.

A Novel Ultrasound Robot with Force/torque Measurement and Control for Safe and Efficient Scanning.

Medical ultrasound is of increasing importance in medical diagnosis and intraoperative assistance and possesses great potential advantages when integrated with robotics. However, some concerns, including the operation efficiency, operation safety, image quality, and comfort of patients, remain after introducing robotics into medical ultrasound. In this paper, an ultrasound robot integrating a force control mechanism, force/torque measurement mechanism, and online adjustment method, is proposed to overcome the current limitations. The ultrasound robot can measure operating forces and torques, provide adjustable constant operating forces, eliminate great operating forces introduced by accidental operations, and achieve various scanning depths based on clinical requirements. The proposed ultrasound robot would potentially facilitate sonographers to find the targets quickly, improve operation safety and efficiency, and decrease patients' discomfort. Simulations and experiments were carried out to evaluate the performance of the ultrasound robot. Experimental results show that the proposed ultrasound robot is able to detect operating force in the z-direction and torques around the x- and y- directions with errors of 3.53% F.S., 6.68% F.S., and 6.11% F.S., respectively, maintain the constant operating force with errors of less than 0.57N, and achieve various scanning depths for target searching and imaging. This proposed ultrasound robot has good performance and would potentially be used in medical ultrasound.