The cGAS-Ku80 complex regulates the balance between two end joining subpathways.

As the major DNA sensor that activates the STING-TBK1 signaling cascade, cGAS is mainly present in the cytosol. A number of recent reports have indicated that cGAS also plays critical roles in the nucleus. Our previous work demonstrated for the first time that cGAS is translocated to the nucleus upon the occurrence of DNA damage and inhibits homologous recombination (HR), one of the two major pathways of DNA double strand break (DSB) repair. However, whether nuclear cGAS regulates the other DSB repair pathway, nonhomologous end joining (NHEJ), which can be further divided into the less error-prone canonical NHEJ (c-NHEJ) and more mutagenic alternative NHEJ (alt-NHEJ) subpathways, has not been characterized. Here, we demonstrated that cGAS tipped the balance of the two NHEJ subpathways toward c-NHEJ. Mechanistically, the cGAS-Ku80 complex enhanced the interaction between DNA-PKcs and the deubiquitinase USP7 to improve DNA-PKcs protein stability, thereby promoting c-NHEJ. In contrast, the cGAS-Ku80 complex suppressed alt-NHEJ by directly binding to the promoter of Polθ to suppress its transcription. Together, these findings reveal a novel function of nuclear cGAS in regulating DSB repair, suggesting that the presence of cGAS in the nucleus is also important in the maintenance of genome integrity.

Accelerometer-measured physical activity, sedentary behavior, and risk of incident pelvic organ prolapse: a prospective cohort study in the UK Biobank.

BACKGROUND: Previous studies on physical activity (PA) and pelvic organ prolapse (POP) were largely limited to self-reported PA in athletes, soldiers, and women in postpartum. We aimed to investigate the association of accelerometer-measured PA and sedentary behavior with the risk of POP in middle-aged and elderly women. METHODS: In this prospective cohort derived from the UK Biobank, the intensity and duration of PA and sedentary behavior were measured with wrist-worn accelerometers over a 7-day period in 2013-2015 for 47,674 participants (aged 42.8-77.9 years) without pre-existing POP. Participants were followed up until the end of 2022, during which incident POP was ascertained mainly by the electronic health records. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to assess the associations of interest. Isotemporal substitution models were applied to test the effects of substituting a type of activity with equivalent duration of others. RESULTS: During a median follow-up of 8.0 years, 779 cases of POP were recorded. The duration of light-intensity PA (LPA) was positively whereas sedentary time was negatively associated with the risk of POP. Every additional 1 h/day of LPA elevated the risk of POP by 18% (95% confidence interval [CI], 10%-26%). In contrast, the risk decreased by 5% (95% CI, 0-8%) per 1 h/day increment in sedentary behavior. No associations were found between moderate-intensity PA (MPA) or vigorous-intensity PA (VPA) and POP, except that women who had a history of hysterectomy were more likely to develop POP when performing more VPA (53% higher risk for every additional 15 min/day). Substituting 1 h/day of LPA with equivalent sedentary time was associated with a 18% (95% CI, 11%-24%) lower risk of POP. The risk can also be reduced by 17% (95% CI, 7%-25%) through substituting 30 min/day of LPA with MPA. CONCLUSIONS: More time spent in LPA or less sedentary time was linked to an elevated risk of POP in middle-aged and elderly women, while MPA or VPA was not. Substituting LPA with equivalent duration of sedentary behavior or MPA may lower the risk of POP.

Androgen signaling stabilizes genomes to counteract senescence by promoting XRCC4 transcription.

Aging is accompanied by a decreased DNA repair capacity, which might contribute to age-associated functional decline in multiple tissues. Disruption in hormone signaling, associated with reproductive organ dysfunction, is an early event of age-related tissue degeneration, but whether it impacts DNA repair in nonreproductive organs remains elusive. Using skin fibroblasts derived from healthy donors with a broad age range, we show here that the downregulation of expression of XRCC4, a factor involved in nonhomologous end-joining (NHEJ) repair, which is the dominant pathway to repair somatic double-strand breaks, is mediated through transcriptional mechanisms. We show that the androgen receptor (AR), whose expression is also reduced during aging, directly binds to and enhances the activity of the XRCC4 promoter, facilitating XRCC4 transcription and thus stabilizing the genome. We also demonstrate that dihydrotestosterone (DHT), a powerful AR agonist, restores XRCC4 expression and stabilizes the genome in different models of cellular aging. Moreover, DHT treatment reverses senescence-associated phenotypes, opening a potential avenue to aging interventions in the future.

Effects of copper oxide nanoparticles on reproductive system of zebrafish.

Copper oxide nanoparticles (CuO NPs) were regarded as the versatile materials in daily life and the in-depth evaluation of their biological effects is of great concern. Herein the female and male zebrafishes were chosen as the model animals to analyze the reproductive toxicity caused by CuO NPs at low concentration (10, 50 and 100 µg/L) After 20-days exposure, the structure of zebrafish ovary and testis were impaired. Moreover, the contents of 17ß-estradiol (E2) in both females and males were increased, while the contents of testosterone (T) were decreased, indicating the imbalanced sex hormones caused by CuO NPs. The expression of genes along the hypothalamic pituitary-gonad (HPG) axis, were examined with quantitative real-time PCR to further evaluate the toxic mechanisms. Meanwhile, the levels of erα/er2ß and cyp19a in female zebrafishes and erα/er2ß, lhr, hmgra/hmgrb, 3ßhsd and 17ßhsd in male zebrafishes were obviously up-regulated. While, the level of αr was obviously down-regulated in female and male zebrafishes. Thus, the obtained data uncovered that long-term exposure of CuO NPs with low dose could trigger the endocrine disorder, resulting in the disturbance of E2 and T level, inhibition of gonad development, and alteration of HPG axis genes. In brief, this study enriched the toxicological data of NPs on aquatic vertebrates and provided the theoretical support for assessing the environmental safety of NPs.

Effectiveness of Laparoscopic Pectopexy for Pelvic Organ Prolapse Compared with Laparoscopic Sacrocolpopexy.

STUDY OBJECTIVE: To evaluate the clinical benefits of laparoscopic pectopexy vs laparoscopic sacrocolpopexy in women with pelvic organ prolapse (POP). DESIGN: Prospective cohort study. SETTING: A tertiary hospital. PATIENTS: We included 203 patients with POP. INTERVENTIONS: Laparoscopic pectopexy or laparoscopic sacrocolpopexy. MEASUREMENTS AND MAIN RESULTS: Anatomic effectiveness was measured using the POP Quantification system, both before and after operation. Functional recovery effectiveness was evaluated using complications and recurrence rates within 1 year. Quality of life was assessed by the Pelvic Floor Distress Inventory-20 and Incontinence Quality of Life questionnaires at enrollment and postoperative months 3, 6, and 12. Comparisons between groups were performed using t test, chi-square test, and mixed-effects model with repeated measures. The analysis included 203 eligible patients (sacrocolpopexy, 101; pectopexy, 102). The proportion of robotic-assisted surgeries was lower in the pectopexy group than in the sacrocolpopexy group (15.7% vs 41.6%, p <.001). The average operation time of pectopexy was shorter than that of sacrocolpopexy (174.2 vs 187.7 minutes) with a mean difference of 13.5 minutes (95% confidence interval, 3.9-23.0; p = .006). Differences of intraoperative blood loss, length of hospital stay, and postoperative 7-day complications between groups were not significant. Anatomic successes were obtained in both groups with similar improvement in POP Quantification scores. The rate of urinary symptoms recurrence was higher in the pectopexy group (13.7%) than in the sacrocolpopexy group (5.0%) at the 1-year follow-up (odds ratio, 3.1; 95% confidence interval, 1.1-8.8, p = .032). The Pelvic Floor Distress Inventory-20 and Incontinence Quality of Life scores were better improved at postoperative months 3, 6, and 12 for laparoscopic pectopexy than for sacrocolpopexy. CONCLUSION: Laparoscopic pectopexy revealed comparable anatomic success, shorter operation time, and better improvement in quality of life scores of prolapse, colorectal-anal, and urinary symptoms at 1-year follow-up, possibly being an alternative when sacrocolpopexy is not practicable. However, clinicians should pay more attention to the recurrence of urinary symptoms after pectopexy.

Association between pelvic floor muscle strength and sexual function based on PISQ-12-an analysis of data from a multicenter cross-sectional study on 735 nulliparae during pregnancy.

Background: Pelvic floor muscle strength is well-known to be associated with female sexual function. However, there were a few studies that reported on the relationship between pelvic floor muscle strength and female sexual function in pregnant women, and the presented results were inconsistent. Nulliparae represent a specific cohort with simplicity to exclude confounding factors that are caused by parity. The present study aimed to explore the association of pelvic floor muscle strength and sexual function based on the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) of nulliparae during pregnancy. Methods: This is the second analysis of the baseline data from a randomized controlled trial (RCT), which aimed to study the protective efficacy of pelvic floor muscle training on stress urinary incontinence at 6th week postpartum (registration number: ChiCTR2000029618). Nulliparae aged 20-40 years with singleton pregnancy before 16 weeks of gestation were enrolled in this study, and data, including participants' demographic information, the Modified Oxford Scale (MOS), and PISQ-12, were collected. Eligible nulliparae were divided into two groups: Group MOS > 3 and Group MOS ≤ 3. Demographic information of the two groups was compared. Sexual function based on the PISQ-12 scores of the two groups was compared. A comparison of the PISQ-12 scores between the two groups was calculated by the Mann-Whitney U-test using SPSS version 23.0. Results: A total of 735 eligible nulliparae were enrolled in this study. Along with MOS grading up, PISQ-12 scores tended to get lower. Of the 735 nulliparae, there were 378 and 357 participants included in Group MOS > 3 and Group MOS ≤ 3, respectively. The PISQ-12 scores of Group MOS > 3 were significantly lower than those of Group MOS ≤ 3 (11 vs. 12, p < 0.001). The scores of the frequency of feeling sexual desire, orgasm achievement, sexual excitement, sexual activity satisfaction, sexual intercourse pain, fear of urinary incontinence, and negative emotion reactions with the sexual intercourse of Group MOS > 3 were lower than those of Group MOS ≤ 3 (p < 0.05). Conclusion: Pelvic floor muscle strength was positively associated with sexual function based on the questionnaire of young nulliparae during their first trimester. Up to half of the nulliparae during the first trimester were suffering from weak pelvic floor muscle strength and nearly a quarter of the nulliparae were facing this weakness combined with sexual dysfunction. Trial registration: This study has been registered at http://www.chictr.org.cn (registration number: ChiCTR2000029618).

Quantitative Assessment of Water Quality Improvement by Reducing External Loadings at Lake Erhai, Southwest China.

To quantitatively evaluate the effects on water quality improvement caused by reducing external loadings entering Lake Erhai through inflow rivers, a one-dimensional hydrodynamic and ecological model (DYRESM-CAEDYM) was set up to simulate the water quality and water level variations. The calibrated and validated model was used to conduct six scenarios for evaluating the water quality responses to different amounts of external loading reduction at Lake Erhai. The results show (1) the total nitrogen (TN) concentration of Lake Erhai will be higher than 0.5 mg/L without any watershed pollution control during April-November 2025, which cannot meet Grade II standard of the China Surface Water Environmental Quality Standards (GB3838-2002). (2) External loading reductions can significantly reduce the concentrations of nutrients and Chla at Lake Erhai. The effects of water quality improvement will be proportional to the reduction rate of external loading reductions. (3) Internal release might be an important source of pollution It needs to be seriously considered as well as external loading for mitigating the eutrophication at Lake Erhai in the future.

Chronic level of exposures to low-dosed MoS2 nanomaterials exhibits more toxic effects in HaCaT keratinocytes.

Molybdenum disulfide nanomaterials (MoS2 NMs) have shown significant role as photocatalysts, lubricating agents and sterilant due to their remarkable physicochemical properties. Because of the increasing demand for MoS2 NMs in numerous industrial domains, greater occupational exposure and subsequent NMs release into environment would be unavoidable. However, much efforts have been made to uncover the biological effects of NMs at unrealistic high concentration or acute duration, placing constraints on setting the realistic occupational exposure thresholds with confidence. In order to fill the current knowledge gap, this study aimed to evaluate the nanotoxicity of MoS2 NMs with or without surface defects under the more realistic exposure mode. Noteworthily, the artificial sweat transformed-occupational exposure-cytotoxicity investigation of MoS2 NMs was established as the main studied line. And the high cellular internalization and augmented oxidative stress triggered by surface defect could be recognized as the main factors for triggering serious cellular damage. Moreover, the HaCaTs exhibited loss of cell membrane integrity, dysfunction of mitochondria, disorder of endoplasmic reticulum and damages of nuclei after chronic exposure, compared with acute exposure. The study provided closely realistic exposure scenarios for NMs which exhibited significant difference from acute toxic investigation, enriching understanding towards real environmental safety of NMs.

Selective versus routine use of episiotomy for vaginal births in Shanghai hospitals, China: a comparison of policies.

BACKGROUND: To assess the effects of policy of selective versus routine episiotomy on mother and baby for women delivering vaginally in Shanghai and whether the hospital type has any effect on the outcomes. METHOD: This was a multi-center retrospective cohort study in Shanghai between March 2015 and May 2017. The study population were vaginal births with selective or routine episiotomy (n = 5478) in 20 secondary or tertiary hospitals. Main Outcome Measure was the incidence of severe perineal lacerations. The adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated by logistic regression and presented as the effect sizes. All models were stratified by the utilization of level (secondary and tertiary) and type (general and Obstetric) of hospital. RESULTS: The primary outcome was not significantly different between vaginal births with routine and selective episiotomy. Patients with selective episiotomy had a lower risk of postpartum hemorrhage, and newborns in the selective episiotomy group had a lower risk of shoulder dystocia and Neonatal Ward compared to those with routine episiotomy. Newborns in selective episiotomy group had a lower risk of birth injury in tertiary hospital. However, newborns in selective episiotomy group had a higher risk of birth injury in general hospitals. CONCLUSION: Selective episiotomy is safe and can be recommended over routine episiotomy in obstetric and tertiary hospital settings in China.

Pregnancy outcomes and associated factors for uterine rupture: an 8 years population-based retrospective study.

BACKGROUND: Uterine rupture is an obstetrical emergency with serious undesired complications for laboring mothers resulting in fatal maternal and neonatal outcomes. The aim of this study was to assess the incidence of uterine rupture, its association with previous uterine surgery and vaginal birth after caesarean section (VBAC), and the maternal and perinatal implications. METHODS: This is a population-based retrospective study. All pregnant women treated for ruptured uterus in one center between 2013 and 2020 were included. Their information retrieved from the medical records department were reviewed retrospectively. RESULTS: A total of 209,112 deliveries were included and 41 cases of uterine rupture were identified. The incidence of uterine rupture was 1.96/10000 births. Among the 41 cases, 16 (39.0%) had maternal and fetal complications. There were no maternal deaths secondary to uterine rupture, while perinatal fatality related to uterine rupture was 7.3%. Among all cases, 38 (92.7%) were scarred uterus and 3 (7.3%) were unscarred uterus. The most common cause of uterine rupture was previous cesarean section, while cases with a history of laparoscopic myomectomy were more likely to have serious adverse outcomes, such as fetal death. 24 (59.0%) of the ruptures occurred in anterior lower uterine segment. Changes in Fetal heart rate monitoring were the most reliable signs for rupture. CONCLUSIONS: Incidence of uterine rupture in the study area, Shanghai, China was consistent with developed countries. Further improvements in obstetric care and enhanced collaboration with referring health facilities were needed to ensure maternal and perinatal safety.

Recent advances in biological applications of nanomaterials through defect engineering.

In recent years, defect engineering sprung up in the artificial nanomaterials (NMs) has attracted significant attention, since the physical and chemical properties of NMs could be largely optimized based on the rational control of different defect types and densities. Defective NMs equipped with the improved electric and catalytic ability, would be widely utilized as the photoelectric device and catalysts to alleviate the growing demands of industrial production and environmental treatments. In particular, considering that the features of targeting, adsorptive, loading and optical could be adjusted by the introduction of defects, numerous defective NMs are encouraged to be applied in the biological fields including bacterial inactivation, cancer therapy and so on. And this review is devoted to summarize the recent biological applications of NMs with abundant defects. Moreover, the opportunity of these defective NMs released into the surrounding environment continue to increase, the direct and indirect contact with biological molecules and organisms would be inevitable. Due to its high reactivity and adsorption triggered by defects, NMs tend to exhibit overestimate biological behaviors and effects on organisms. Thus, the sections regarding toxicological effects of NMs with abundant defects are also carried out to supplement the safety assessments of NMs and guide further applications in the industrial production and living.

Robotic Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Resection of Parametrial and Bowel Deeply Infiltrated Endometriosis.

STUDY OBJECTIVE: To demonstrate stepwise techniques for the successful utilization of the Robotic-assisted transvaginal Natural Orifice Transluminal Endoscopy Surgery (NOTES) technique for safely surgically managing deeply infiltrated endometriosis (DIE). DESIGN: Stepwise demonstration with narrated video footage. SETTING: An academic tertiary care hospital. INTERVENTIONS: A 38-year-old woman-G3P3, who had 1 normal spontaneous vaginal delivery and 1 cesarean delivery for twin pregnancy-with worsening chronic pelvic pain. History of laparoscopic ablation of endometriosis 10 years ago. Magnetic resonance imaging demonstrated adenomyosis, deeply infiltrated endometriosis, and intrapelvic adhesions. Robotic transvaginal NOTES hysterectomy has been demonstrated to be feasible and safe in the surgical management of benign gynecology disease compared with traditional NOTES hysterectomy; however, it can be technically challenging to perform, particularly in managing of additional deep infiltrated endometriosis removal surgery after hysterectomy. The researchers demonstrated that robotic vaginal NOTES surgeries are feasible in complex benign gynecologic procedures such as endometriosis and sacrocolpopexy [1-3]. The robotic wristed instruments with 3D visualization, resulting in delicate tissue dissection and easier suturing and knot tying, are beneficial to surgeons for overcoming the cumbersome surgical techniques in transvaginal NOTES complete endometriosis removal [4,5]. Integration of robotic transvaginal single site surgery and resection of DIE is a novel alternative minimally invasive route that is more cosmetic and less painful. The procedure was successfully performed in approximately 200 minutes, with unevenly postoperative recovery. The patient was discharged home the same day. Her pain level was 7 out of 10 in the first week, 5 out of 10 in the second week, and 2 out of 10 in the third week. Pathology confirmed uterine adenomyosis, endometriosis in the right ureteral, right uterine artery pedicle, and rectum with muscular propria involvement. CONCLUSION: Robotic transvaginal NOTES for deeply invasive endometriosis is challenging but feasible in patients with parametrial and rectal involvement. The advantages of articulating instrumentation and 3D visualization are especially pivotal in complex transvaginal NOTES surgery.

Machine learning-based rapid diagnosis of human borderline ovarian cancer on second-harmonic generation images.

Regarding growth pattern and cytological characteristics, borderline ovarian tumors fall between benign and malignant, but they tend to develop malignancy. Currently, it is difficult to accurately diagnose ovarian cancer using common medical imaging methods, and histopathological examination is routinely used to obtain a definitive diagnosis. However, such examination requires experienced pathologists, being labor-intensive, time-consuming, and possibly leading to interobserver bias. By using second-harmonic generation imaging and k-nearest neighbors classifier in conjunction with automated machine learning tree-based pipeline optimization tool, we developed a computer-aided diagnosis method to classify ovarian tissues as being malignant, benign, borderline, and normal, obtaining areas under the receiver operating characteristic curve of 1.00, 0.99, 0.98, and 0.97, respectively. These results suggest that diagnosis based on second-harmonic generation images and machine learning can support the rapid and accurate detection of ovarian cancer in clinical practice.

Shifts in Vaginal Bacterial Community Composition Are Associated With Vaginal Mesh Exposure.

OBJECTIVE: The objective of this study was to evaluate the relationship between vaginal mesh exposure and vaginal bacterial community composition. METHODS: Vaginal swab samples were collected from 13 women undergoing excision of vaginal mesh with vaginal mesh exposure. Samples were collected at the midvagina, site of exposure, and underneath the vaginal epithelium at the exposure. Control samples were collected vaginally during 15 new patient examinations. For all samples, we extracted genomic DNA and polymerase chain reaction amplified and sequenced the 16S rRNA gene V4 region. We tested for differences in the microbiota among control and exposure samples with PERMANOVA tests of beta diversity measures (Morisita-Horn dissimilarity) and Wilcoxon rank sum tests of Lactobacillus distribution. RESULTS: Vaginal bacterial communities in both control and case groups were divided into 2 primary community types, one characterized by Lactobacillus dominance (>50% of community) and the other by low Lactobacillus and a high diversity of vaginal anaerobes. In 10 of 13 case women, bacterial communities were highly similar between the 3 vaginal sites (adonis R2 = 0.86, P = 0.0099). In the 3 women with community divergence, all 3 were characterized by decreased Lactobacillus abundance at the exposure site. Overall, Lactobacillus abundance was lower at the site of mesh exposure and under the epithelium than in the experimental control (W = 137, P = 0.072, r = 0.41; W = 146, P = 0.025, r = 0.50). Common putative pathogenic mesh colonizing bacteria were common (in 51 of 54 samples), but generally not abundant (median relative abundance = 0.014%). CONCLUSIONS: In vaginal mesh exposure cases, a woman is more likely to have a diverse, non-Lactobacillus-dominant community.

The synergistic effect of enhanced photocatalytic activity and photothermal effect of oxygen-deficient Ni/reduced graphene oxide nanocomposite for rapid disinfection under near-infrared irradiation.

The rational design of high antibacterial efficiency are urgently needed as the occurrence of drug-resistance issues. Hence, Ni/reduced graphene oxide nanocomposite (Ni/rGO) with different amounts of oxygen vacancies were fabricated for efficient disinfection. The optimized Ni/rGO (A100) exhibited highly effective inactivation efficacy of 99.6% and 99.5% against Escherichia coli and Bacillus subtilis within 8 min near-infrared (NIR) irradiation through the synergistic effects of photothermal therapy and oxidative damage, which were much higher than single treatment. The A100 nanocomposite achieved an extraordinary photothermal conversion efficiency (35.78%) under the 808 nm irradiation for enhanced photothermal hyperthermia, thereby destroying the cell membrane and accelerating the GSH depletion. The radical scavenger experiment confirmed that •O2- and •OH play the chief role in photodisinfection reaction. Besides, A100 could exert significant damage on the ATP synthesis. The excellent photothermal performance and photocatalytic activity can be attributed to the appropriate oxygen vacancy density, which improves the absorption of NIR light and facilitates the separation of photogenerated electron-hole pairs. Besides, the higher NiO content of A100 contributed to improving the photocatalytic effect. Our work demonstrated a promising strategy for efficient water pollution purification caused by pathogenic bacteria.

Less is more: biological effects of NiSe2/rGO nanocomposites with low dose provide new insight for risk assessment.

Nickel selenide nanomaterials (NiSe2 NMs) with different vacancies demonstrated high catalytic activity as electrocatalyst in oxygen evolution reaction. As the growing needs of the industrial applications in electrocatalyst, the increased occupational exposure and environmental releasing of NMs would be unavoidable. While, much efforts have been made to evaluate the ecological safety of such engineered NMs at unrealistically high concentrations, failed to provide the comprehensively guideline for exposure thresholds. To supplement the current knowledge gap, we testified the cytotoxicity of NiSe2/rGO nanocomposites with different surface defects under more realistic exposure mode. Compared with the short-term exposure and repetitive exposure, rat lung macrophages exhibited the augmented oxidative stress, dysfunction of mitochondria, damage of DNA and disorder of calcium homeostasis under the long-term NiSe2/rGO exposure. Noteworthily, no significant differences could be found between the NiSe2/rGO with different surface defects, indicated that the defect type of NMs were not the accurate predictor for real risk assessment. Collectively, the study provided the real potential toxic effects and exposure thresholds of NMs that might be highly possible industrial produced, and appealed the new insight for risk assessments of engineered NMs under the long-term exposure, which exhibited difference from the traditional evaluation of short-term and repetitive exposure.

Vacancy-Enhanced Photothermal Killing of Bacteria Mediated by Graphene Oxide.

With the emergence of antibiotic resistance, the development of efficient antimicrobial agents has become increasingly important. Graphene oxide (GO) has been used as an antibacterial agent, but how to realize and improve the antibacterial properties of GO is still required critically. Herein, we prepared two GO samples, abbreviated as GO-V11 and GO-V9. Positron annihilation spectra showed that they possessed predominantly VCCCCCCCCCCC (V11C) and VCCCCCCCCC (V9C) carbon vacancies, respectively. Their photothermal antibacterial properties were measured against Gram-negative Escherichia coli (E. coli) and Gram-positive Bacillus subtilis (B. subtilis) by using colony-forming unit and liquid optical density assays. GO-V9 displayed a higher photothermal antibacterial efficiency toward the two bacteria than GO-V11 because GO-V9 had a higher photothermal conversion efficiency (PTCE) (57.3%) than GO-V11 (42.5%). To reveal the difference in their PTCEs and antibacterial efficiencies, their energy band structures were tested with density functional theory calculations. The different vacancies changed the energy band structure from the indirect band gap of GO-V11 to the quasi-metallic band gap of GO-V9. The quasi-metallic band gap showed the higher PTCE, so we revealed the importance of the band gap of GO for its antibacterial mechanism. Tuning the vacancy properties is promising for improving the photothermal antibacterial efficiency.

Maintenance Therapy Can Improve the Oncologic Prognosis and Obstetrical Outcome of Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer After Fertility-Preserving Treatment: A Multicenter Retrospective Study.

OBJECTIVE: To evaluate the effect of maintenance therapy for patients with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) after successful fertility-preserving management on prognosis and pregnancy outcome. METHODS: We performed a retrospectively analysis of 109 young women with atypical endometrial hyperplasia and early endometrioid endometrial cancer who had received complete response after fertility-preserving treatment at 5centers between May 2005 and March 2021. Maintenance therapy regimes included low-dose oral progesterone, levonorgestrel intrauterine device(LNG-IUD) and combination oral contraceptive (COC). The patients were divided into two groups, maintenance therapy group and non-maintenance therapy group. Clinical characteristics, treatment regimens, prognosis, and pregnancy outcome were compared between the two groups. RESULTS: The overall disease recurrence rate of the maintenance therapy group was significantly lower than that of the non-maintenance therapy group (P < 0.001). The recurrence rate of atypical endometrial hyperplasia and endometrial cancer in the maintenance therapy group were significantly lower than those in the non-maintenance group (P < 0.001). Maintenance therapy can reduce pregnancy rates and live birth rates. Maintenance therapy can protect the endometrium in patients treated with assisted reproductive technology (ART), greatly reducing the recurrence rate after ART (P<0.001). CONCLUSION: Maintenance therapy plays a very important protective role in fertility-preserving treatment for patients with atypical endometrial hyperplasia and endometrial cancer, which could significantly reduce the risk of recurrence. It is recommended that patients could receive maintenance therapy as long as possible during the period from achieving complete response to pregnancy preparation if possible. It may provide recurrence-free survival long enough for childless young women to prepare for pregnancy in the future. It can also protect the endometrium of those who are preparing to use assisted reproductive technology, possibly by reducing the risk of recurrence by excessive stimulation with assisted reproductive drugs.

Vacancy-induced toxicity of CoSe2 nanomaterials in rat lung macrophages.

Rich vacancies of semiconductor nanomaterials (NMs) give rise to great enhancement of their physical and chemical properties such as magnetic, catalytic, optical, etc. These NMs possessing extensive applications could inevitably enter into the environment and increase the toxic effects on organisms, so it is imperative to investigate the cytotoxicity of NMs with different types of vacancies. Here, one-dimensional cobalt selenide (CoSe2) NMs with different vacancies were synthesized through the same precursor while calcined at different temperatures (P-CoSe2 which calcined at 200 °C and N-CoSe2 which calcined at 230 °C). According to the positron annihilation spectrum, the VSeSe vacancy associate in P-CoSe2 was endowed with two positive charges, while the VCoCoCoSeSe vacancy associate in N-CoSe2 possessed four negative charges. Cell viability assays revealed that N-CoSe2 had higher toxicity to macrophages than P-CoSe2, which was attributed to higher levels of intracellular reactive oxygen species induced by N-CoSe2. Further investigation showed that N-CoSe2 had higher affinity to the mitochondrion-targeting peptide, leading to its preferential distribution in the mitochondria and consequent induction of mitochondrial superoxide production. In contrast, P-CoSe2 exhibited higher affinity to the endoplasmic reticulum (ER)-targeting peptide, facilitating its preferential distribution in the ER and the nuclei and causing higher damage to both organelles as compared to N-CoSe2. These results demonstrated that type of surface vacancies significantly affected biodistribution of NMs in subcellular organelles, which contributed to differential biological behaviors of the NMs.

Targeting specific cell organelles with different-faceted nanocrystals that are selectively recognized by organelle-targeting peptides.

Targeting specific cellular organelles is an elusive therapeutic goal that could be achieved by manipulating nanocrystal facets. As proof of concept, different facet-engineered nanonods (high-energy (001) CdS and (001) CdSe, and low-energy (101) CdS and (110) CdSe) exploited selective binding by organelle-targeting peptides and subsequent intracellular protein sorting to inhibit specific organelles without significant cytotoxicity.