Comparison of capture-based mtDNA sequencing performance between MGI and illumina sequencing platforms in various sample types.

BACKGROUND: Mitochondrial genome abnormalities can lead to mitochondrial dysfunction, which in turn affects cellular biology and is closely associated with the development of various diseases. The demand for mitochondrial DNA (mtDNA) sequencing has been increasing, and Illumina and MGI are two commonly used sequencing platforms for capture-based mtDNA sequencing. However, there is currently no systematic comparison of mtDNA sequencing performance between these two platforms. To address this gap, we compared the performance of capture-based mtDNA sequencing between Illumina's NovaSeq 6000 and MGI's DNBSEQ-T7 using tissue, peripheral blood mononuclear cell (PBMC), formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and urine samples. RESULTS: Our analysis indicated a high degree of consistency between the two platforms in terms of sequencing quality, GC content, and coverage. In terms of data output, DNBSEQ-T7 showed higher rates of clean data and duplication compared to NovaSeq 6000. Conversely, the amount of mtDNA data obtained by per gigabyte sequencing data was significantly lower in DNBSEQ-T7 compared to NovaSeq 6000. In terms of detection mtDNA copy number, both platforms exhibited good consistency in all sample types. When it comes to detection of mtDNA mutations in tissue, FFPE, and PBMC samples, the two platforms also showed good consistency. However, when detecting mtDNA mutations in plasma and urine samples, significant differenceof themutation number detected was observed between the two platforms. For mtDNA sequencing of plasma and urine samples, a wider range of DNA fragment size distribution was found in NovaSeq 6000 when compared to DNBSEQ-T7. Additionally, two platforms exhibited different characteristics of mtDNA fragment end preference. CONCLUSIONS: In summary, the two platforms generally showed good consistency in capture-based mtDNA sequencing. However, it is necessary to consider the data preferences generated by two sequencing platforms when plasma and urine samples were analyzed.

Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084.

HPTN 084 demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with daily oral tenofovir disoproxil fumarate-emtricitabine (F/TDF) for HIV prevention in women. CAB-LA (600 mg) or placebo injections were administered 4 weeks after an initial dose (loading dose) and every 2 months (Q2M) thereafter; this is the approved regimen. Participants experienced both loading dose and Q2M delays during the trial. CAB concentrations were evaluated before a delay, at the visit associated with the delay, and the visit after a delayed injection was administered. During the blinded phase of the trial, 194 participants randomized to CAB-LA experienced at least one injection delay. Plasma CAB concentrations were maintained above the 4× protein adjusted 90% inhibitory concentration (4× PA-IC90; protocol-specific threshold) for all loading dose and 98% of Q2M delays when injections were administered up to 6 weeks late. The feasibility of shifting to an every 3-month (Q3M) regimen in females was interrogated via simulation studies using a population pharmacokinetic model. Q3M injections in both CAB-naïve (with a loading dose) and previously CAB-exposed females were predicted to yield higher steady-state exposures than in males on the approved Q2M regimen. Although there is observed forgiveness following an isolated delayed CAB-LA injection and simulations suggest acceptable CAB-LA exposures in women with a 600 mg CAB-LA Q3M regimen, empirical efficacy of this regimen has not been established, and transitioning to this dosing schema is not recommended. Future pharmacokinetic bridging studies are aimed at evaluating higher dose CAB-LA formulations administered less frequently. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03164564.

Crystal structure of exfoliative toxin D from Staphylococcus aureus.

Staphylococcus aureus exfoliative toxins (ETs) are serine proteases responsible for staphylococcal scalded skin syndrome. Four ETs, ETA, ETB, ETD, and ETE, have been identified, all of which cleave desmoglein-1. This study presents the crystal structure of ETD at 1.75 Å resolution. The protein exhibits a structure composed of two ß-barrels and two α-helices as described in previous studies of ETs. A predicted model of ETD in complex with Ile380-Glu381-Gly382-Pro383 (IEGP), a segment of human desmoglein-1 (hDsg1), was constructed. Glu381 of hDsg1 was predicted to interact with as many as six amino acid residues in ETD, whereas two amino acid residues in ETD primarily constituted subsite S1', and a space near subsite S1' was noted. It is likely that polypeptide chains located near the IEGP segment in the predicted structure of hDsg1 bind to this space. The structure of loop D, which was predicted to participate in subsite S2', in ETD was markedly different from those in other ETs.

Tryptophan-rich diet and its effects on Htr7+ Tregs in alleviating neuroinflammation and cognitive impairment induced by lipopolysaccharide.

BACKGROUND: Neuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer's, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role. METHODS: Mice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1-/-) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7. RESULTS: In this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1-/- mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment. CONCLUSIONS: Our research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Electrical Stimulation Promotes Endocytosis of Magnetic Nanoparticles by Cancer Cells.

Nanomaterials are increasingly used in biomedical imaging and cancer therapy, and how to improve the endocytosis of nanomaterials by cells is a key issue. The application of alternating current (AC) electrical stimulation to osteosarcoma cells (MG-63) here can increase the cellular endocytosis of Fe3O4 nanoparticles (diameter: 50 nm) by 52.46% via macropinocytosis. This can be ascribed to the decrease in F-actin content and the increase in intracellular Ca2+ concentration. Transmission electron microscope, immunofluorescence staining, western blot, flow cytometry, and inductively coupled plasma emission spectrometer analyses support this interpretation. The application of electrical stimulation decreases the cell viability in magnetic hyperthermia by 47.6% and increases the signal intensity of magnetic resonance imaging by 29%. Similar enhanced endocytosis is observed for breast cancer cells (MCF-7), glioblastoma cells (U-87 MG), melanoma cells (A-375), and bladder cancer cells (TCCSUP), and also for Fe3O4 nanoparticles with the diameters of 20 and 100 nm, and Zn0.54Co0.46Cr0.65Fe1.35O4 nanoparticles with the diameter of 70 nm. It seems the electrical stimulation has the potential to improve the diagnostic and therapeutic effects of magnetic nanoparticles by promoting endocytosis.

A computational framework to unify orthogonal information in DNA methylation and copy number aberrations in cell-free DNA for early cancer detection.

Cell-free DNA (cfDNA) provides a convenient diagnosis avenue for noninvasive cancer detection. The current methods are focused on identifying circulating tumor DNA (ctDNA)s genomic aberrations, e.g. mutations, copy number aberrations (CNAs) or methylation changes. In this study, we report a new computational method that unifies two orthogonal pieces of information, namely methylation and CNAs, derived from whole-genome bisulfite sequencing (WGBS) data to quantify low tumor content in cfDNA. It implements a Bayes model to enrich ctDNA from WGBS data based on hypomethylation haplotypes, and subsequently, models CNAs for cancer detection. We generated WGBS data in a total of 262 samples, including high-depth (>20×, deduped high mapping quality reads) data in 76 samples with matched triplets (tumor, adjacent normal and cfDNA) and low-depth (~2.5×, deduped high mapping quality reads) data in 186 samples. We identified a total of 54 Mb regions of hypomethylation haplotypes for model building, a vast majority of which are not covered in the HumanMethylation450 arrays. We showed that our model is able to substantially enrich ctDNA reads (tens of folds), with clearly elevated CNAs that faithfully match the CNAs in the paired tumor samples. In the 19 hepatocellular carcinoma cfDNA samples, the estimated enrichment is as high as 16 fold, and in the simulation data, it can achieve over 30-fold enrichment for a ctDNA level of 0.5% with a sequencing depth of 600×. We also found that these hypomethylation regions are also shared among many cancer types, thus demonstrating the potential of our framework for pancancer early detection.

Observation and all-optical manipulation of replica symmetry breaking dynamics in a multi-Stokes-involved Brillouin random fiber laser photonic system.

In this paper, we propose and demonstrate an all-optical control of RSB transition in a multi-wavelength Brillouin random fiber laser (MWBRFL). Multi-order Stokes light components can be subsequently generated by increasing the power of the Erbium-doped fiber amplifier (EDFA) inside the MWBRFL, providing additional disorder as well as multiple Stokes-involved interplay. It essentially allows diversified laser mode landscapes with adjustable average mode lifetime and random mode density of the 1st order Stokes, which benefits the switching between replica symmetry breaking (RSB) and replica symmetry (RS) states in an optically controlled manner. Results show that the average mode lifetime of the 1st order Stokes component gradually decreases from 250.0 ms to 1.2 ms as high orders from the 2nd to the 5th of Stokes components are activated. Meanwhile, the order parameter q of the 1st order Stokes random lasing emission presents distinct statistical distributions within the selective sub-window under various EDFA optical powers. Consequently, all-optical dynamical control of the 1st Stokes random laser mode landscapes with adjustable average mode lifetime turns out to be attainable, facilitating the RSB transition under an appropriate observation time window. These findings open a new avenue for exploring the underlying physical mechanisms behind the occurrence of the RSB phenomenon in photonic complex systems.

Optical proximity correction of hot-spot patterns with subwavelength size in DMD maskless projection lithography.

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.

Sub-kHz-linewidth broadband-swept fiber laser based on Rayleigh scattering-enabled Brillouin random lasing oscillation with dynamic tunning Brillouin gain spectrum.

A sub-kHz-linewidth broadband-swept fiber laser using Rayleigh scattering-based Brillouin random lasing oscillation is proposed and experimentally demonstrated. Benefiting from Brillouin-involved acoustic damping and arbitrary-wavelength distributed Rayleigh feedback, leveraging instantaneously tuning Brillouin gain spectrum induced by a frequency-sweeping pump, a highly coherent random lasing emission with cavity mode elimination as well as frequency noise suppression is achieved in a sweeping manner. Results show that the proposed sweeping Stokes laser with a two-order-magnitude compressed linewidth of 840 Hz and 20 dB frequency noise suppression can unprecedentedly operate over the maximum wavelength range of 16 nm. Dynamic characteristics of the sweeping laser frequency are experimentally investigated, indicating a minimum residual nonlinearity of 0.0001 within the frequency-sweeping range of 126.63 GHz. It is believed that the proposed swept fiber laser may have attractive potential in diverse applications, including sensing and imaging.

Enhancing Fenton-like Degradation of Organic Pollutants at Neutral pH by Multivalent Cu NCs/HAp Nanocatalysts.

Heterogeneous Fenton-like catalysis is a widely used method for the degradation of organic pollutants. However, it still has some limitations such as low activity in the neutral condition, low conversion rates of metals with different valence states, and potential secondary metal pollution. In this study, a Fenton-like nanocatalyst was first created by generating ultrasmall copper nanoclusters (Cu NCs) on the surface of hydroxyapatite (HAp) through a process of doping followed by modification. This resulted in the formation of a composite nanocatalyst known as Cu NCs/HAp. With the help of hydrogen peroxide (H2O2), Cu NCs/HAp exhibits an outstanding Fenton-like catalytic performance by efficiently degrading organic dyes such as methylene blue under mild neutral conditions. The removal rate can reach over 83% within just 30 min, demonstrating ideal catalytic universality and stability. The improved Fenton-like catalytic performance of Cu NCs/HAp can be ascribed to the synergistic effect of the multivalent Cu species through two simultaneous reaction pathways. During route I, the embedded Cu NCs with a core-shell Cu0/Cu+ structure can undergo sequential oxidation to form Cu2+, which continuously activates H2O2 to generate hydroxyl radicals (•OH) and singlet oxygen (1O2). In route II, Cu2+ produced from route I and initially adsorbed on the surface of HAp can be reduced by H2O2, thus regenerating Cu+ species for route I and achieving a closed-loop reaction. This work has confirmed that Cu NCs loaded on HAp may be an alternative Fenton-like catalyst for degradation of organic pollutants and environmental remediation, opening up new avenues for potential applications of other Cu NCs in future water pollution control.

Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.

Interest in I-PrEP and Willingness to Participate in Clinical Trials Among Men and Transfeminine Persons Who have Sex with Men in Sub-Saharan Africa: Quantitative and Qualitative Findings from HPTN 075.

This study explored interest in injectable PrEP (I-PrEP) and willingness to participate in clinical trials testing new biomedical HIV prevention strategies among men and transfeminine persons who have sex with men (MSM & TGP), using data collected in the HIV Prevention Trials Network (HPTN) 075 study, which took place at sites in Kenya, Malawi, and South Africa. Data result from a survey among 267 18-44 years old HIV negative participants, complemented with semi-structured interviews with 80 purposively recruited persons. Correlations coefficients were calculated to identify demographic and psychosocial factors associated with interest in I-PrEP. Qualitative interviews were analyzed using concept-driven and subsequent data-driven coding. Most surveyed participants expressed an interest in I-PrEP. Quantitatively, only being interested in other HIV prevention measures was associated with interest in I-PrEP. Qualitatively, most participants preferred I-PrEP to O-PrEP and remained interested in I-PrEP despite barriers such as the somewhat invasive nature of the procedure and potential side effects of I-PrEP. Interest in I-PrEP was driven by the possibility of avoiding sexual or HIV stigma. Access to healthcare and altruism-such as assisting in the development of new HIV prevention methods-positively impacted willingness to participate in clinical trials. With I-PrEP favored by most participants, it is potentially a critical tool to prevent HIV infection among MSM & TGP in sub-Saharan Africa, with the mitigation of stigma as a major advance. Recruitment of MSM & TGP in biobehavioral clinical trials seems feasible, with altruistic reasons and receiving I-PrEP and free medical care as major motivators.

RESUMEN: Este estudio exploró el interés en la PrEP inyectable (I-PrEP) y la voluntad de participar en ensayos clínicos que prueban nuevas estrategias biomédicas de prevención del VIH entre hombres y personas transfemeninas que tienen sexo con hombres (HSH y TGP), utilizando datos recopilados en la Red de Ensayos de Prevención del VIH. (HPTN) 075, que se llevó a cabo en sitios de Kenia, Malawi y Sudáfrica. Los datos son el resultado de una encuesta entre 267 participantes VIH negativos de entre 18 y 44 años, complementada con entrevistas semiestructuradas con 80 personas reclutadas intencionalmente. Se calcularon coeficientes de correlación para identificar factores demográficos y psicosociales asociados con el interés en la I-PrEP. Las entrevistas cualitativas se analizaron mediante codificación basada en conceptos y, posteriormente, basada en datos. La mayoría de los participantes encuestados expresaron interés en la I-PrEP. Cuantitativamente, sólo estar interesado en otras medidas de prevención del VIH se asoció con el interés en la I-PrEP. Cualitativamente, la mayoría de los participantes prefirieron la I-PrEP a la O-PrEP y siguieron interesados en la I-PrEP a pesar de barreras como la naturaleza algo invasiva del procedimiento y los posibles efectos secundarios de la I-PrEP. El interés en la I-PrEP fue impulsado por la posibilidad de evitar el estigma sexual o del VIH. El acceso a la atención sanitaria y el altruismo (como la asistencia en el desarrollo de nuevos métodos de prevención del VIH) tuvieron un impacto positivo en la voluntad de participar en ensayos clínicos. Dado que la mayoría de los participantes prefieren la I-PrEP, es potencialmente una herramienta crítica para prevenir la infección por VIH entre HSH y TGP en el África subsahariana, con la mitigación del estigma como un avance importante. El reclutamiento de HSH y TGP en ensayos clínicos bioconductuales parece factible, con razones altruistas y recibir I-PrEP y atención médica gratuita como principales motivadores.

A cytokine-like factor 1 homolog acts as a macrophage chemoattractant in grass carp.

Cytokine-like factor 1 (CYTL1) is a small cytokine and has diverse biological functions in mammals. However, whether CYTL1 exists in lower vertebrates is not clear. In this study, we identified cytl homologs in fish and characterized the immune functions in a teleost species, grass carp (Ctenopharyngodon idella). Fish CYTL1 homologs share conserved molecular features with their mammalian counterparts, including 6 cysteine residues in the mature peptide, genomic organization and synteny. Gene expression analysis revealed that cytl1 was constitutively expressed in tissues of grass carp, with the highest expression detected in the heart. Upon infection with Aeromonas hydrophila (A. hydrophila), cytl1 was downregulated in the hindgut, head kidney, skin, and spleen. In the primary head kidney leukocytes (HKLs), stimulation with inactivated A. hydrophila, LPS, poly(I:C), IL-22, IFN-a or IFN-γrel resulted in downregulation of cytl1 expression. Recombinant grass carp CYTL1 protein produced in the HEK293-F cells was potent to induce il-10 expression, but had little effect on the expression of il-1ß and il-6. In vivo experiments revealed that CYTL1 was effective to recruit macrophages to the muscle injected with cytl expression plasmids. Taken together, our results indicate that CYTL1 is a potent chemokine for recruitment of macrophages in fish.

Clinical study on the necessity and feasibility of routine MRCP in patients with cholecystolithiasis before LC.

BACKGROUND: In the past quite a long time, intraoperative cholangiography(IOC)was necessary during laparoscopic cholecystectomy (LC). Now magnetic resonance cholangiopancreatography (MRCP) is the main method for diagnosing common bile duct stones (CBDS). Whether MRCP can replace IOC as routine examination before LC is still inconclusive. The aim of this study was to analyze the clinical data of patients undergoing LC for cholecystolithiasis, and to explore the necessity and feasibility of preoperative routine MRCP in patients with cholecystolithiasis. METHODS: According to whether MRCP was performed before operation, 184 patients undergoing LC for cholecystolithiasis in the Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University from January 1, 2017 to December 31, 2018 were divided into non-MRCP group and MRCP group for this retrospective study. The results of preoperative laboratory test, abdominal ultrasound and MRCP, biliary related comorbidities, surgical complications, hospital stay and hospitalization expenses were compared between the two groups. RESULTS: Among the 184 patients, there were 83 patients in non-MRCP group and 101 patients in MRCP group. In MRCP group, the detection rates of cholecystolithiasis combined with CBDS and common bile duct dilatation by MRCP were higher than those by abdominal ultrasound (P < 0.05). The incidence of postoperative complications in non-MRCP group (8.43%) was significantly higher (P < 0.05) than that in MRCP group (0%). There was no significant difference in hospital stay (P > 0.05), but there was significant difference in hospitalization expenses (P < 0.05) between the two groups. According to the stratification of gallbladder stone patients with CBDS, hospital stay and hospitalization expenses were compared, and there was no significant difference between the two groups (P > 0.05). CONCLUSIONS: The preoperative MRCP can detect CBDS, cystic duct stones and anatomical variants of biliary tract that cannot be diagnosed by abdominal ultrasound, which is helpful to plan the surgical methods and reduce the surgical complications. From the perspective of health economics, routine MRCP in patients with cholecystolithiasis before LC does not increase hospitalization costs, and is necessary and feasible.

Association between serum carotenoids and bacterial vaginosis infection among American women.

BACKGROUND: Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. METHOD: The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. RESULT: Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and ß-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and ß-carotene became significantly negatively correlated with BV. CONCLUSION: This study found an inverse correlation between serum carotenoids and the prevalence of BV.

An intramolecular charge transfer based fluorescent probe for imaging of OCl.

The discovery and utilization of new fluorescent chromophore is indispensable to exploit high performance probes for biological research. Stokes shift is one of the most important properties of chromophore accounting for super-resolution fluorescence imaging. Intramolecular charge transfer (ICT) is one of the fundamental mechanisms for fluorescence that accompanied by large Stokes shifts. Based on the conformational changes between ground and excited states, ICT models can be divided into two types: conformation-steady ICT, whose conformation remains unchanged, and conformation-changeable ICT, which is characterized by the rotation of the chromophore around an axis upon excitation. Herein, we report a new chromophore whose donor and acceptor parts took a butterfly geometry with a dihedral angle of 21° in ground state and a planar conformation upon photo excitation. The bent conformation might be ascribed to the extra conjugated double bond, which made the coplanarity of the chromophore in ground state get worse. The chromophore shows a remarkable Stokes shift over 150 nm and a high fluorescence quantum yieldof 0.62. The limit of detection is 41 nM, which enabled the imaging of basal as well as induced OCl- in different cells. Moreover, the pronounced spectroscopic properties ensure the in vivo monitoring of OCl- in arthritic mice. This finding would shed light on the exploitation of small molecule probes based on new fluorescence chromophore for precise biological imaging.

Feasibility, safety and efficacy of high intensity focused ultrasound ablation as a preoperative treatment for challenging hysteroscopic myomectomy.

PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.

Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status.

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

Association between serum vitamin E and bacterial vaginitis in women: a cross-sectional study.

INTRODUCTION: Bacterial vaginitis (BV) is a common vaginal disease. Vitamin E has been shown to reduce BV by enhancing immune function, but no studies have analyzed the relationship between vitamin E and BV at different BMIs and ages. METHOD: This study used 2242 participants from four cycles of NHANES 1999-2006 in American. Participants' vitamin E levels were divided into four groups, and analyses such as study population description, stratified analysis, multiple logistic regression analysis, and curve fitting were performed. To perform data processing, the researchers used the statistical package R (The R Foundation; http://www.r-project.org ; version 3.6.3) and Empower Stats software ( www.empowerstats.net , X&Y solutions, Inc. Boston, Massachusetts). RESULT: The concentrations of serum vitamin E were negatively correlated with the risk of BV, especially when vitamin E were at 1198-5459ug/dL with (OR = -0.443, 95%CI = 0.447-0.923, P = 0.032) or without (OR = -0.521, 95%CI = 0.421-0.837, P = 0.006) adjustment for variables. At the same time, at lower levels, there was no significant association. Vitamin E supplementation may significantly reduce the risk of BV (p < 0.001). In addition, the risk of having BV decreased and then increased with increasing vitamin E concentrations at high BMI levels (p < 0.01). CONCLUSION: Vitamin E at moderate to high concentrations may significantly reduce BV risk, says the study, providing clinical evidence for the prevention and the treatment of BV.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.