Energy-efficient dispersion compensation for digital micromirror device.

Due to the wave nature of light, the diffraction pattern generated by an optical device is sensitive to the shift of wavelength. This fact significantly compromises the digital micromirror device (DMD) in applications, such as full-color holographic display and multi-color fluorescence microscopy. The existing dispersion compensation techniques for DMD involve adding diffractive elements, which causes a large amount of waste of optical energy. Here, we propose an energy-efficient dispersion compensation method, based on a dispersive prism, for DMD. This method simulates the diffraction pattern of the optical fields reflected from the DMD with an angular spectrum model. According to the simulation, a prism and a set of optical components are introduced to compensate for the angular dispersion of DMD-modulated optical fields. In the experiment, our method reduced the angular dispersion, between the 532 nm and 660 nm light beams, by a factor of ∼8.5.

U. Parvum serovars exhibit distinct pathogenicity in Chinese women of childbearing age: a multicentre cross-sectional study.

BACKGROUND: Ureaplasma spp. can be classified into different serovars. It is unknown whether distinct serovars are associated with clinical signs and symptoms. METHODS: We conducted a multicentre cross-sectional study. U. parvum serovars were identified on the basis of their multiple-banded antigen (MBA) genes. After adjusting for demographic variables and other reproductive tract infections, the odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the impact of U. parvum serovars on clinical symptoms. RESULTS: Among 5,277 individuals, U. parvum serovars 3 and 6 were the most prevalent serovars (17.9% and 16.0%, respectively). Potential confounders, such as age, body mass index (BMI), ethnicity, education level, contraceptive methods, number of sexual partners, gravidity, parity, and other sexually transmitted infections (STIs) that are associated with clinical symptoms (P < 0.1) were adjusted for in the univariate analysis. U. parvum serovar 14 was strongly positively associated with certain clinical symptoms, including redness and swelling of the vaginal wall (crude OR: 3.53, 95% CI: 1.92-6.49; adjusted OR: 5.21, 95% CI: 2.56-10.58), cervical bleeding and swelling (crude OR: 3.89, 95% CI: 2.38-6.36; adjusted OR: 7.37, 95% CI: 3.82-14.23), and cervical ectropion (crude OR: 2.08, 95% CI: 1.25-3.45; adjusted OR: 3.04, 95% CI: 1.60-5.74). In contrast, U. parvum serovar 3 was negatively associated with a variety of clinical symptoms, whereas no correlations were detected between U. parvum serovars 1and 6 with clinical symptoms. CONCLUSIONS: Different U. parvum serovars exhibit distinct correlations with clinical symptoms, suggesting that U. parvum serovars are pathogenically heterogeneous and that further differentiation of serovars may be necessary. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( https://www. CLINICALTRIALS: gov ; ID: NCT04694495; Registration Date: 2021-01-05).

A short peptide exerts neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis.

BACKGROUND: Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. METHODS: A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. RESULTS: A new peptide (NP1) with an amino acid sequence of 'FLPAAICLVIKTC' was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood-brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase ß (IKKß). IKKß reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. CONCLUSIONS: The newly discovered non-toxic peptide NP1 ('FLPAAICLVIKTC') exerted neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

Peptide OA-VI12 restrains melanogenesis in B16 cells and C57B/6 mouse ear skin via the miR-122-5p/Mitf/Tyr axis.

Excessive melanogenesis leads to hyperpigmentation, which is one of the common skin conditions in humans. Existing whitening cosmetics cannot meet market needs due to their inherent limitations. Thus, the development of novel skin-whitening agents continues to be a challenge. The peptide OA-VI12 from the skin of amphibians at high altitude has attracted attention due to its remarkable anti light damage activity. However, whether OA-VI12 has the skin-whitening effect of inhibiting melanogenesis is still. Mouse melanoma cells (B16) were used to study the effect of OA-VI12 on cell viability and melanin content. The pigmentation model of C57B/6 mouse ear skin was induced by UVB and treated with OA-VI12. Melanin staining was used to observe the degree of pigmentation. MicroRNA sequencing, quantitative real-time PCR (qRT-PCR), immunofluorescence analysis and Western blot were used to detect the change of factor expression. Double luciferase gene report experiment was used to prove the regulatory relationship between miRNA and target genes. OA-VI12 has no effect on the viability of B16 cells in the concentration range of 1-100 µM and significantly inhibits the melanin content of B16 cells. Topical application of OA-VI12, which exerted transdermal potency, prevented UVB-induced pigmentation of ear skin. MicroRNA sequencing and double luciferase reporter analysis results showed that miR-122-5p, which directly regulated microphthalmia-associated transcription factor (Mitf), had significantly different expression before and after treatment with OA-VI12. Mitf is a simple helix loop and leucine zipper transcription factor that regulates tyrosinase (Tyr) expression by binding to the M-box promoter element of Tyr. qRT-PCR, immunofluorescence analysis and Western blot showed that OA-VI12 up-regulated the expression of miR-122-5p and inhibited the expression of Mitf and Tyr. The effects of OA-VI12 on melanogenesis inhibition in vitro and in vivo may involve the miR-122-5p/Mitf/tyr axis. OA-VI12 represents the first report on a natural amphibian-derived peptide with skin-whitening capacity and the first report of miR-122-5p as a target for regulating melanogenesis, thereby demonstrating its potential as a novel skin-whitening agent and highlighting amphibian-derived peptides as an underdeveloped resource.

A frog peptide provides new strategies for the intervention against skin wound healing.

BACKGROUND: Amphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing. METHODS: Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing. RESULTS: The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3ß to activate Wnt/ß-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/ß-catenin to promote full-thickness skin wound healing in rats. CONCLUSIONS: OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/ß-catenin molecular axis). Moreover, miR-632 also activated Wnt/ß-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates.

Purslane-induced oxalate nephropathy: case report and literature review.

BACKGROUND: The kidney is particularly vulnerable to toxins due to its abundant blood supply, active tubular reabsorption, and medullary interstitial concentration. Currently, calcium phosphate-induced and calcium oxalate-induced nephropathies are the most common crystalline nephropathies. Hyperoxaluria may lead to kidney stones and progressive kidney disease due to calcium oxalate deposition leading to oxalate nephropathy. Hyperoxaluria can be primary or secondary. Primary hyperoxaluria is an autosomal recessive disease that usually develops in childhood, whereas secondary hyperoxaluria is observed following excessive oxalate intake or reduced excretion, with no difference in age of onset. Oxalate nephropathy may be overlooked, and the diagnosis is often delayed or missed owning to the physician's inadequate awareness of its etiology and pathogenesis. Herein, we discuss the pathogenesis of hyperoxaluria with two case reports, and our report may be helpful to make appropriate treatment plans in clinical settings in the future. CASE PRESENTATION: We report two cases of acute kidney injury, which were considered to be due to oxalate nephropathy in the setting of purslane (portulaca oleracea) ingestion. The two patients were elderly and presented with oliguria, nausea, vomiting, and clinical manifestations of acute kidney injury requiring renal replacement therapy. One patient underwent an ultrasound-guided renal biopsy, which showed acute tubulointerstitial injury and partial tubular oxalate deposition. Both patients underwent hemodialysis and were discharged following improvement in creatinine levels. CONCLUSIONS: Our report illustrates two cases of acute oxalate nephropathy in the setting of high dietary consumption of purslane. If a renal biopsy shows calcium oxalate crystals and acute tubular injury, oxalate nephropathy should be considered and the secondary causes of hyperoxaluria should be eliminated.

miR-186-5p targets TGFßR2 to inhibit RAW264.7 cell migration and proliferation during mouse skin wound healing.

BACKGROUND: Active peptides play a vital role in the development of new drugs and the identification and discovery of drug targets. As the first reported native peptide homodimer with pro-regenerative potency, OA-GP11d could potentially be used as a novel molecular probe to help elucidate the molecular mechanism of skin wound repair and provide new drug targets. METHODS: Bioinformatics analysis and luciferase assay were adopted to determine microRNAs (miRNAs) and its target. The prohealing potency of the miRNA was determined by MTS and a Transwell experiment against mouse macrophages. Enzyme-linked immunosorbent assay, realtime polymerase chain reaction, and western blotting were performed to explore the molecular mechanisms. RESULTS: In this study, OA-GP11d was shown to induce Mus musculus microRNA-186-5p (mmu-miR-186-5p) down-regulation. Results showed that miR-186-5p had a negative effect on macrophage migration and proliferation as well as a targeted and negative effect on TGF-ß type II receptor (TGFßR2) expression and an inhibitory effect on activation of the downstream SMAD family member 2 (Smad2) and protein-p38 kinase signaling pathways. Importantly, delivery of a miR-186-5p mimic delayed skin wound healing in mice. CONCLUSION: miR-186-5p regulated macrophage migration and proliferation to delay wound healing through the TGFßR2/Smad2/p38 molecular axes, thus providing a promising new pro-repair drug target.

Disturbance of hepatocyte growth and metabolism in a hyperammonemia microenvironment.

BACKGROUND: We found through previous research that hyperammonemia can cause secondary liver damage. However, whether hepatocytes are target cells of ammonia toxicity and whether hyperammonemia affects hepatocyte metabolism remain unknown. AIMS: The purpose of the current study is to examine whether the hepatocyte is a specific target cell of ammonia toxicity and whether hyperammonemia can interfere with hepatocyte metabolism. METHODS: Cell viability and apoptosis were analyzed in primary hepatocytes and other cells that had been exposed to ammonium chloride. Western blotting was adopted to examine the expression of proteins related to ammonia transport. We also established a metabolomics method based on gas chromatography-mass spectrometry to understand the characteristics of the hepatocyte metabolic spectrum in a hyperammonemia microenvironment, to screen and identify differential metabolites, and to determine the differential metabolic pathway. Different technologies were used to verify the differential metabolic pathways. RESULTS: Hepatocytes are target cells of ammonia toxicity. The mechanism is related to the ammonia transporter. Hyperammonemia interferes with hepatocyte metabolism, which leads to TCA cycle, urea cycle, and RNA synthesis disorder. CONCLUSIONS: This study demonstrates that hepatocyte growth and metabolism are disturbed in a hyperammonemia microenvironment, which further deteriorates hepatocyte function.

The relationship between menopausal syndrome and gut microbes.

BACKGROUND: Gut microbes were closely related to women's health. Previous studies reported that the gut microbes of premenopausal women were different from those of postmenopausal women. However, little was known about the relationship between gut microbiota dysbiosis and menopausal syndrome (MPS). The aim of this study was to explore the relationship between MPS and gut microbes. METHODS: Patients with MPS (P group, n = 77) and healthy women (H group, n = 24) at menopause were recruited in this study. The stool specimen and clinical parameters (demographic data, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), et al) of participants' were collected. We evaluated the differences in gut microbes by 16S ribosomal RNA gene sequencing. We used LEfSe to identify gut microbes with varying abundances in different groups. The Spearman correlation coefficients of clinical parameters and gut microbes were calculated. PICRUSt was used to predict the potential KEGG Ortholog functional profiles of microbial communities. RESULTS: The abundance of 14 species differed substantially between the MPS and menopausal healthy women (LDA significance threshold > 2.0) according to LEfSe analysis. Using Spearman's correlation analysis, it was discovered that E2 had a positive correlation with Aggregatibacter segnis, Bifidobacterium animalis, Acinetobacter guillouiae (p < 0.05, these three species were enriched in menopausal healthy women), while FSH and LH had a negative correlation with them (p < 0.05). KEGG level3 metabolic pathways relevant to cardiovascular disease and carbohydrate metabolism were enriched in the MPS (p < 0.05), according to functional prediction by PICRUST and analyzed by Dunn test. CONCLUSION: There was gut microbiota dysbiosis in MPS, which is reflected in the deficiency of the abundance of Aggregatibacter segnis, Bifidobacterium animalis and Acinetobacter guillouiae related to the level of sex hormones. In MPS individuals, species with altered abundances and unique functional pathways were found.

Probiotics are a good choice for the treatment of bacterial vaginosis: a meta-analysis of randomized controlled trial.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common vaginal infectious diseases in female reproductive period. Although the existing view is that probiotic treatment may be one of the feasible methods for the treatment of BV, different intervention methods lead to different treatment results. Therefore, up-to-date and comprehensive evidence in this regard is essential for the development of intervention strategies. OBJECTIVE: This meta-analysis aims to systematically evaluate the role of probiotics in the treatment of BV in adult women. METHODS: We searched the databases of Embase, Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov for Randomized Controlled Trials published until November 7, 2021. Meta-analysis was performed by Revman5.3 software to systematically evaluate the clinical efficacy of probiotics adjunctive therapy in the treatment of BV. The literatures were screened and evaluated according to the inclusion and exclusion criteria. Chi-square test was used to test the heterogeneity between trials. Random or Fixed effect models were used to analyze the cure rate of BV. RESULTS: Fourteen randomized controlled trials compared the efficacy of probiotics with antibiotic therapy (probiotics + antibiotics group) versus antibiotics alone or plus placebo (antibiotics (+ placebo) group) for BV [Risk Ratios (RR) = 1.23, 95% CI (1.05, 1.43), P = 0.009]. Three compared the efficacy of probiotics regimen (probiotics group) and antibiotics (antibiotics group) in the treatment of BV [RR = 1.12, 95% CI (0.60, 2.07), P = 0.72]. Another Three compared the efficacy of probiotics regimen (probiotics group) with placebo (placebo group) [RR = 15.20, 95% CI (3.87, 59.64), P < 0.0001]. CONCLUSION: Our meta-analysis suggests probiotics may play a positive role in the treatment of BV, but more strong evidence is needed.

Our meta-analysis found that probiotics may play an active role in adjuvant treatment of bacterial vaginosis by conventional antibiotic therapy. It was emphasized that oral administration of L. rhamnose was more effective than vaginal application of L. rhamnose in the treatment of bacterial vaginosis. The therapeutic effect of probiotics varies with the administration route and dosage of probiotics.

Dietary Fiber and Human Papillomavirus Infection among US Women: The National Health and Nutrition Examination Survey, 2003-2016.

The impact of dietary fiber on human papillomavirus (HPV) infection is still underway. The aim of our study was to investigate the association between intake of dietary fiber and HPV infection. Overall, 14,151 eligible women, aged 18-59 years old, who submitted an adequate sample for HPV test, were collected from an ongoing, large scale population-based survey for seven cycles. The association of dietary fiber intake and HPV infection was assessed in multivariate logistic models. For sensitivity analysis, generalized additive model (GAM) and smooth curve fitting were employed to verify the robustness of the results. Among 14,151 eligible participants, intake of dietary fiber was negatively associated with HPV infection. Each additional increase in log10 dietary fiber consumption was associated with a 57% lower risk of HPV infection (OR, 0.43; 95% CI 0.38-0.48). The result is stable in minimally and fully adjusted model. The possibility of nonlinear association of dietary fiber and HPV infection has been excluded by GAM and smooth curve fitting. There was an inverse linear correlation between intake of dietary fiber and HPV infection. Our findings obtained from NHANES dataset suggested that increasing dietary fiber consumption may be associated with the prevalence of HPV infection.

sncRNAs packaged by Helicobacter pylori outer membrane vesicles attenuate IL-8 secretion in human cells.

Bacterial outer membrane vesicles (OMVs) play a vital role in the mechanism of host-pathogen communication, while emerging evidence suggests that OMVs regulate host immune responses through differentially packaged small noncoding RNAs (sncRNAs) to target host mRNA function. Therefore, we identified differentially packaged sncRNAs in Helicobacter pylori OMVs and showed transfer of OMV sncRNAs to human gastric adenocarcinoma cells in this study. Our data revealed that sncRNAs (sR-2509025 and sR-989262) were enriched in OMVs, and reduced lipopolysaccharide or OMV-induced interleukin 8 (IL-8) secretion by cultured AGS cells. Collectively, these findings are consistent with the hypothesis that sncRNAs in H. pylori OMVs play a novel role in the mechanism of host-pathogen interaction, whereby H. pylori evades the host immune response.

A Model to Predict Treatment Failure of Single­Dose Methotrexate in Patients with Tubal Pregnancy.

BACKGROUND In China, approximately 15% of tubal pregnancy patients treated with MTX eventually required surgery because the ectopic mass was ruptured; therefore, it is essential to develop a model to predict the risk of failure with methotrexate treatment in tubal pregnancy. MATERIAL AND METHODS In this research, 168 patients met the eligibility criteria, and 29 candidate risk factors for treatment failure were collected. Multivariable logistic regression analysis was used to analyze the factors, and a full model was developed. We used a multiple fractional polynomial model and a stepwise model to increase the reliability. Bootstrap resampling for 500 times was used to internally test the prediction model. The integral performance of the model depends on the evaluation of the nomogram, the discriminative performance by receiver operating characteristic (ROC) curve analysis, and calibration. RESULTS The model showed excellent discrimination and calibration. The area under the ROC curve for the prediction model, mfp model, and stepwise model were 0.879 (95% CI: 0.812-0.942), 0.872 (95% CI: 0.805-0.931), and 0.880 (95% CI: 0.817-0.949), respectively. At a cutoff value of ≥0.40, sensitivity was 60%, specificity was 91%, positive predictive value (PPV) was 81%, and negative predictive value (NPV) was 77%. The model provides a net benefit when clinical decision thresholds are between 0% and 40% of predicted risk. CONCLUSIONS This model indicated good accuracy in predicting methotrexate treatment failure for tubal pregnancy patients.

Association of Thiamine Intake with Human Papillomavirus (HPV) Infection in American Women: A Secondary Data Analysis Based on the National Health and Nutrition Examination Survey from 2003 to 2016.

BACKGROUND Studies have shown that thiamine intake is associated with cervical cancer, but the relationship between thiamine and HPV infection remains unclear. In the present study, we used the National Health and Nutrition Examination Survey (NHANES) database to investigate whether HPV infection was associated with thiamine intake. MATERIAL AND METHODS A total of 13 471 women ages 18-59 years were selected from the NHANES database from 2003 to 2016. Using thiamine intake as the independent variable, HPV infection as the dependent variable, and sociodemographic data and other data as the covariates, we analyzed the relationship between thiamine and HPV infection by conducting a weighted logistic regression model in a cross-sectional research design. RESULTS The two-piecewise linear model indicated the inflection point of thiamine intake was 2.07 mg. On the left side of the inflection point, the difference in the thiamine intake of log2 conversion was related to the difference of 0.82 in HPV infection, which means that the increase of every 1 unit increase in thiamine intake is associated with the decrease of the HPV infection by 18%. On the right side of the inflection point, we did not observe a correlation between HPV infection and thiamine intake. CONCLUSIONS Thiamine intake is negatively correlated with HPV infection. Intake of an appropriate amount of thiamine can prevent HPV infection. The best preventive effect can be achieved when the intake is about 2 mg, and excessive intake will not increase the preventive effect.

A Piezoelectric Tactile Sensor for Tissue Stiffness Detection with Arbitrary Contact Angle.

In this paper, a piezoelectric tactile sensor for detecting tissue stiffness in robot-assisted minimally invasive surgery (RMIS) is proposed. It can detect the stiffness not only when the probe is normal to the tissue surface, but also when there is a contact angle between the probe and normal direction. It solves the problem that existing sensors can only detect in the normal direction to ensure accuracy when the degree of freedom (DOF) of surgical instruments is limited. The proposed senor can distinguish samples with different stiffness and recognize lump from normal tissue effectively when the contact angle varies within [0°, 45°]. These are achieved by establishing a new detection model and sensor optimization. It deduces the influence of contact angle on stiffness detection by sensor parameters design and optimization. The detection performance of the sensor is confirmed by simulation and experiment. Five samples with different stiffness (including lump and normal samples with close stiffness) are used. Through blind recognition test in simulation, the recognition rate is 100% when the contact angle is randomly selected within 30°, 94.1% within 45°, which is 38.7% higher than the unoptimized sensor. Through blind classification test and automatic k-means clustering in experiment, the correct rate is 92% when the contact angle is randomly selected within 45°. We can get the proposed sensor can easily recognize samples with different stiffness with high accuracy which has broad application prospects in the medical field.

Anti-GPC3 Antibody Tagged Cationic Switchable Lipid-Based Nanoparticles for the Co-Delivery of Anti-miRNA27a And Sorafenib in Liver Cancers.

PURPOSE: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy. METHODS: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system. RESULTS: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation. CONCLUSION: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers.

A hybrid method for provincial scale energy-related carbon emission allocation in China.

Achievement of carbon emission reduction targets proposed by national governments relies on provincial/state allocations. In this study, a hybrid method for provincial energy-related carbon emissions allocation in China was developed to provide a good balance between production- and consumption-based approaches. In this method, provincial energy-related carbon emissions are decomposed into direct emissions of local activities other than thermal power generation and indirect emissions as a result of electricity consumption. Based on the carbon reduction efficiency principle, the responsibility for embodied emissions of provincial product transactions is assigned entirely to the production area. The responsibility for carbon generation during the production of thermal power is borne by the electricity consumption area, which ensures that different regions with resource endowments have rational development space. Empirical studies were conducted to examine the hybrid method and three indices, per capita GDP, resource endowment index and the proportion of energy-intensive industries, were screened to preliminarily interpret the differences among China's regional carbon emissions. Uncertainty analysis and a discussion of this method are also provided herein.

Species-level resolution for the vaginal microbiota with short amplicons.

Specific bacterial species have been found to play important roles in human vagina. Achieving high species-level resolution is vital for analyzing vaginal microbiota data. However, contradictory conclusions were yielded from different methodological studies. More comprehensive evaluation is needed for determining an optimal pipeline for vaginal microbiota. Based on the sequences of vaginal bacterial species downloaded from NCBI, we conducted simulated amplification with various primer sets targeting different 16S regions as well as taxonomic classification on the amplicons applying different combinations of algorithms (BLAST+, VSEARCH, and Sklearn) and reference databases (Greengenes2, SILVA, and RDP). Vaginal swabs were collected from participants with different vaginal microecology to construct 16S full-length sequenced mock communities. Both computational and experimental amplifications were performed on the mock samples. Classification accuracy of each pipeline was determined. Microbial profiles were compared between the full-length and partial 16S sequencing samples. The optimal pipeline was further validated in a multicenter cohort against the PCR results of common STI pathogens. Pipeline V1-V3_Sklearn_Combined had the highest accuracy for classifying the amplicons generated from both the NCBI downloaded data (84.20% ± 2.39%) and the full-length sequencing data (95.65% ± 3.04%). Vaginal samples amplified and sequenced targeting the V1-V3 region but merely employing the forward reads (223 bp) and classified using the optimal pipeline, resembled the mock communities the most. The pipeline demonstrated high F1-scores for detecting STI pathogens within the validation cohort. We have determined an optimal pipeline to achieve high species-level resolution for vaginal microbiota with short amplicons, which will facilitate future studies.IMPORTANCEFor vaginal microbiota studies, diverse 16S rRNA gene regions were applied for amplification and sequencing, which affect the comparability between different studies as well as the species-level resolution of taxonomic classification. We conducted comprehensive evaluation on the methods which influence the accuracy for the taxonomic classification and established an optimal pipeline to achieve high species-level resolution for vaginal microbiota with short amplicons, which will facilitate future studies.

Peptide OM-LV20 promotes arteriogenesis induced by femoral artery ligature via the miR-29b-3p/VEGFA axis.

BACKGROUND AND AIMS: Therapeutic arteriogenesis is a promising direction for the treatment of ischemic disease caused by atherosclerosis. However, pharmacological or biological approaches to stimulate functional collateral vessels are not yet available. Identifying new drug targets to promote and explore the underlying mechanisms for therapeutic arteriogenesis is necessary. METHODS: Peptide OM-LV20 (20 ng/kg) was administered for 7 consecutive days on rat hindlimb ischemia model, collateral vessel growth was assessed by H&E staining, liquid latex perfusion, and specific immunofluorescence. In vitro, we detected the effect of OM-LV20 on human umbilical vein endothelial cells (HUVEC) proliferation and migration. After transfection, we performed quantitative real-time polymerase chain reaction, in situ-hybridization and dual luciferase reporters to assessed effective miRNAs and target genes. The proteins related to downstream signaling pathways were detected by Western blot. RESULTS: OM-LV20 significantly increased visible collateral vessels and endothelial nitric oxide synthase (eNOS), together with enhanced inflammation cytokine and monocytes/macrophage infiltration in collateral vessels. In vitro, we defined a novel microRNA (miR-29b-3p), and its inhibition enhanced proliferation and migration of HUVEC, as well as the expression of vascular endothelial growth factor A (VEGFA). OM-LV20 also promoted migration and proliferation of HUVEC, and VEGFA expression was mediated via inhibition of miR-29b-3p. Furthermore, OM-LV20 influenced the protein levels of VEGFR2 and phosphatidylinositol3-kinase (PI3K)/AKT and eNOS in vitro and invivo. CONCLUSIONS: Our data indicated that OM-LV20 enhanced arteriogenesis via the miR-29b-3p/VEGFA/VEGFR2-PI3K/AKT/eNOS axis, and highlighte the application potential of exogenous peptide molecular probes through miRNA, which could promote effective therapeutic arteriogenesis in ischemic conditions.

Breakthrough of chemiluminescence-based LAM urine test beyond HIV-positive individuals: Clinical diagnostic value of pulmonary tuberculosis in the general population.

To investigate the diagnostic value of a novel high-sensitivity urine lipoarabinomannan (LAM) test (chemiluminescence-based) for active tuberculosis in the general population. A retrospective study was conducted on 250 clinical suspected tuberculosis patients who were HIV-negative and visited the Fourth People's Hospital of Foshan from January 2022 to December 2022. Among them, there were 135 cases of pulmonary tuberculosis, 34 cases of extrapulmonary tuberculosis, and 81 cases of non-tuberculosis. Urine samples were collected for LAM antigen detection before treatment, and laboratory data of sputum smear acid-fast staining (smear method), sputum culture, and GeneXpert method were collected. Using clinical diagnosis as the reference standard, the diagnostic efficacy of 4 methods for detecting active tuberculosis was evaluated. For the 135 cases of pulmonary tuberculosis, the sensitivity of sputum smears, sputm culture, sputm GeneXpert method, and urine LAM were 29.6% (40/135), 45.9% (62/135), 59.3% (80/135), and 51.9% (70/135), respectively. The combination of LAM + GeneXpert and LAM + culture had the highest sensitivity for detecting active pulmonary tuberculosis, which were 71.0% and 78.2%, respectively. For the detection of sputum culture-negative pulmonary tuberculosis, the positive rates of smear, GeneXpert, and LAM were 0.0% (0/73), 53.4% (39/73), and 52.1% (38/73), respectively. LAM + smear and LAM + Genexpert could detect 52.1% and 68.5% of sputum culture-negative patients, respectively. The high-sensitivity urine LAM test holds promise for tuberculosis diagnosis in the general population. It demonstrates high-sensitivity, enabling the detection of sputum culture-negative pulmonary tuberculosis patients. Furthermore, when combined with existing methods, it can enhance the overall detection rate.