AP collagen peptides (APCPs) promote hair growth by activating the GSK-3ß/ß-catenin pathway and improve hair condition.

AP collagen peptides (APCPs) are enzymatically decomposed collagen peptides that contain tri-peptides such as glycine-proline-hydroxyproline. We found that APCPs increased the proliferation of both human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). APCPs also stimulated the secretion of several growth factors, including IGFBP-6, PDGF-AB, PIGF and VEGF in hDPCs. Moreover, APCPs enhanced the phosphorylation of Akt(Ser473), GSK-3ß(Ser9) and ß-catenin(Ser675), indicating the activation of the GSK-3ß/ß-catenin signalling pathway. Ex vivo culture of human hair follicles (hHFs) tissue and in vivo patch assay revealed that APCPs promoted the elongation of hHFs and the induction of new hair shafts. In a mouse model, APCPs significantly promoted the transition from telogen to anagen phase and prolonged anagen phase, resulting in increased hair growth. APCPs also improved the thickness, amino acid content (cystine and methionine) and roughness of mouse hair. Taken together, these findings demonstrate that APCPs accelerate hair growth and contribute to overall hair health. Therefore, APCPs have the potential to be utilized as a food supplement and ingredient for preventing hair loss and maintaining hair health.

Irisin promotes hair growth and hair cycle transition by activating the GSK-3ß/ß-catenin pathway.

Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF-1, FGF and irisin are reprehensive myokines. Although VEGF, IGF-1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/ß-catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF-1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/ß-catenin signalling inhibitor, suppressed the irisin-mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/ß-catenin pathway and highlight its therapeutic potential in hair loss treatment.

Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced atopic dermatitis (AD) via PPARα.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell-free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast-neonatal-derived exosome (HDFn-Ex) on AD. HDFn-Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1-chloro-2,4-dinitrobenzene (DNCB)-mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn-Ex significantly inhibited DNCB-induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB-induced AD-like mouse model, HDFn-Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn-Ex. These effects were blocked by pre-treatment with GW6471. Furthermore, HDFn-Ex exhibited an anti-inflammatory effect by inhibiting the DNCB-induced increases in IκBα phosphorylation and TNF-α expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn-Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti-inflammatory activity.

A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib.

OBJECTIVE: Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD). METHODS: Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity. RESULTS: In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23). CONCLUSIONS: Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

Hepatitis B Virus DNA-Level Change is Associated With Tumor Recurrence in Patients With Resected Hepatitis B Virus Hepatocellular Carcinoma.

INTRODUCTION: To investigate the significance of perioperative hepatitis B virus (HBV) DNA changes for predicting recurrence in patients with HBV-related hepatocellular carcinoma (HCC) undergoing liver resection (LR). METHODS: From 2013 to 2020, 241 patients with HBV-related HCC who underwent LR in five Hallym university-affiliated hospitals were enrolled. The serum HBV DNA level, together with other clinicopathological variables, was analyzed for association with HCC recurrence. RESULTS: Preoperatively, 99 patients had undetectable HBV DNA and 142 had detectable viral levels. Of those with detectable viral levels, 72 rapidly progressed to undetectable levels within 3 mo after LR (Rapid group), and 70 showed persistently detectable levels (Nonrapid group). The Rapid group had a better recurrence-free survival (RFS) rate than the Nonrapid group (1-y, 3-y RFS = 75.4%, 57.3%, versus 54.7%, 39.9%, respectively, P = 0.012). In the subgroup analysis, the Rapid group had a better RFS rate in early stages (1-y, 3-y RFS = 82.6%, 68.5%, versus 62.8%, 45.8%, respectively, P = 0.005); however, the RFS rates between the two groups were comparable in the advanced stage (1-y, 3-y RFS = 61.1%, 16.7% versus 45.5%, 22.7%, respectively, P = 0.994). Among the 142 patients with preoperatively detectable HBV DNA, persistently detectable HBV DNA within 3 mo postoperatively (hazard ratio [HR] = 1.7, P = 0.022), large tumor size (HR = 2.7, P < 0.001), multiple tumors (HR = 3.2, P < 0.001), and microvascular invasion (HR = 1.7, P = 0.028) were independent risk factors for RFS in multivariate analysis. CONCLUSIONS: Rapidly undetectable HBV DNA after LR is associated with a better prognosis for recurrence in patients with HCC. Therefore, appropriate treatment and/or screening may be necessary for patients who do not return to undetectable HBV DNA after LR.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study.

BACKGROUND: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.

Apple Watch 6 vs. Galaxy Watch 4: A Validity Study of Step-Count Estimation in Daily Activities.

The purpose of this study was to examine the validity of two wearable smartwatches (the Apple Watch 6 (AW) and the Galaxy Watch 4 (GW)) and smartphone applications (Apple Health for iPhone mobiles and Samsung Health for Android mobiles) for estimating step counts in daily life. A total of 104 healthy adults (36 AW, 25 GW, and 43 smartphone application users) were engaged in daily activities for 24 h while wearing an ActivPAL accelerometer on the thigh and a smartwatch on the wrist. The validities of the smartwatch and smartphone estimates of step counts were evaluated relative to criterion values obtained from an ActivPAL accelerometer. The strongest relationship between the ActivPAL accelerometer and the devices was found for the AW (r = 0.99, p < 0.001), followed by the GW (r = 0.82, p < 0.001), and the smartphone applications (r = 0.93, p < 0.001). For overall group comparisons, the MAPE (Mean Absolute Percentage Error) values (computed as the average absolute value of the group-level errors) were 6.4%, 10.5%, and 29.6% for the AW, GW, and smartphone applications, respectively. The results of the present study indicate that the AW and GW showed strong validity in measuring steps, while the smartphone applications did not provide reliable step counts in free-living conditions.

Injectable Ventral Spinal Stimulator Evokes Programmable and Biomimetic Hindlimb Motion.

Spinal cord neuromodulation can restore partial to complete loss of motor functions associated with neuromotor disease and trauma. Current technologies have made substantial progress but have limitations as dorsal epidural or intraspinal devices that are either remote to ventral motor neurons or subject to surgical intervention in the spinal tissue. Here, we describe a flexible and stretchable spinal stimulator design with nanoscale thickness that can be implanted by minimally invasive injection through a polymeric catheter to target the ventral spinal space of mice. Ventrolaterally implanted devices exhibited substantially lower stimulation threshold currents and more precise recruitment of motor pools than did comparable dorsal epidural implants. Functionally relevant and novel hindlimb movements were achieved via specific stimulation patterns of the electrodes. This approach holds translational potential for improving controllable limb function following spinal cord injury or neuromotor disease.

A 13-Year Trend Analysis of HIV Epidemiology in the Philippines (2010 to 2022).

PURPOSE: This article describes the trends and contributing factors in the human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) epidemiology in the Philippines from 2010 to 2022. This is the first trend analysis of the Philippine HIV/AIDS situation. DESIGN: Using time trend research design, 13-year longitudinal epidemiological data were collected and analyzed to present a dynamic perspective of the Philippine HIV/AIDS epidemic. METHODS: Secondary data analysis of HIV surveillance public documents from 2010 to 2022 was conducted. The Centers for Disease Control's socioecological model was used to guide the literature and interpretation of findings. Frequency, percentage distribution, and Sieve-bootstrap t-test for linear trends were used to analyze the results. FINDINGS: There is an increased trend in HIV incidence, late diagnosis, and AIDS-related mortality in all geographical regions in the country from 2010-2022. The majority of HIV cases are males, ages 25-34, and reside in the nation's capital. Increased HIV incidence among overseas workers, sex workers, and HIV-positive blood products were noted. CONCLUSION: Trends in Philippine HIV epidemiology are contrary to global trends. Community-based HIV prevention programs targeting specific high-risk populations are needed. CLINICAL EVIDENCE: Community health nurses in the Philippines play a critical role in reversing the rising trend of HIV/AIDS. They are positioned to lead targeted education and prevention programs for high-risk groups using the socioecological model to implement community-based strategies that address factors contributing to the epidemic. Their efforts in early detection and linkage to care are essential in reducing late diagnosis and AIDS-related mortality.

A Single-Arm, Open-Label Phase II Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma.

BACKGROUND: ONC201 is a small molecule that can cause nonapoptotic cell death through loss of mitochondrial function. Results from the phase I/II trials of ONC201 in patients with refractory solid tumors demonstrated tumor responses and prolonged stable disease in some patients. METHODS: This single-arm, open-label, phase II clinical trial evaluated the efficacy of ONC201 at the recommended phase II dose (RP2D) in patients with recurrent or refractory metastatic breast or endometrial cancer. Fresh tissue biopsies and blood were collected at baseline and at cycle 2 day 2 for correlative studies. RESULTS: Twenty-two patients were enrolled; 10 patients with endometrial cancer, 7 patients with hormone receptor-positive breast cancer, and 5 patients with triple-negative breast cancer. The overall response rate was 0%, and the clinical benefit rate, defined by complete response (CR) + partial response (PR) + stable disease (SD), was 27% (n = 3/11). All patients experienced an adverse event (AE), which was primarily low grade. Grade 3 AEs occurred in 4 patients; no grade 4 AEs occurred. Tumor biopsies did not show that ONC201 consistently induced mitochondrial damage or alterations in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the TRAIL death receptors. ONC201 treatment caused alterations in peripheral immune cell subsets. CONCLUSION: ONC201 monotherapy did not induce objective responses in recurrent or refractory metastatic breast or endometrial cancer at the RP2D dose of 625 mg weekly but had an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03394027).

NRF2-mediated SIRT3 induction protects hepatocytes from ER stress-induced liver injury.

Chronic endoplasmic reticulum (ER) stress in hepatocytes plays a role in the pathogenesis of nonalcoholic fatty liver disease. Therefore, given the association between oxidative stress, mitochondrial dysfunction, and ER stress, our study investigated the role of NRF2-mediated SIRT3 activation in ER stress. SIRT3, a sirtuin, was predicted as the target of NRF2 based on bioinformatic analyses and animal experiments. Nrf2 abrogation diminished mitochondrial DNA content in hepatocytes with Ppargc1α and Cpt1a inhibition, whereas its overexpression enhanced oxygen consumption. Further, chromatin immunoprecipitation and luciferase reporter assays indicated that NRF2 induced SIRT3 through the antioxidant responsive element (ARE) sites comprising the -641 to -631 bp and -419 to -409 bp regions. In tunicamycin-induced ER stress conditions and liver injury animal models following ER stress, NRF2 levels were highly correlated with SIRT3. Nrf2 deficiency enhanced the tunicamycin-mediated induction of CHOP, which was attenuated by Sirt3 overexpression. Further, Sirt3 delivery to hepatocytes in Nrf2 knockout mice prevented tunicamycin from increasing mortality by decreasing ER stress. SIRT3 was upregulated in livers of patients with nonalcoholic liver diseases, whereas lower SIRT3 expression coincided with more severe disease conditions. Taken together, our findings indicated that NRF2-mediated SIRT3 induction protects hepatocytes from ER stress-induced injury, which may contribute to the inhibition of liver disease progression.

A comparison of dyeing efficacy between hair-oxidation-based and hair-coating-based shampoos for the treatment of gray hair.

BACKGROUND: The process of hair dyeing causes hair damage, and periodic re-dyeing is required for newly grown hair. To avoid these hassles, hair color shampoos have been developed and are widely used. In this study, we compared the effects of two hair color shampoos with different dyeing principles to analyze the function of hair color shampoos. We analyzed hair tresses treated by hair-oxidation- and hair-coating-based shampoos. MATERIALS AND METHODS: We measured the color, tensile properties, softness, elasticity, gloss, moisture content, and protein content of the hair tresses dyed with color shampoos. The hair structures were analyzed by scanning and transmission electron microscopies (SEM and TEM) and a hydroxy radical-based method. RESULTS: The shampoo based on hair coating enhanced the hair dyeing effect and roughness, whereas that based on hair oxidation improved the color retention and moisture content in the hair tresses. Frictional resistance, gloss, and elasticity of the hair tresses were similar for the two products. However, according to the results of the protein loss test, TEM, and hydroxyl radical staining, the shampoo based on hair oxidation showed a longer dyeing retention compared to that based on hair coating but caused cuticle damage. CONCLUSION: These results show that the two shampoos with different dyeing principles exhibit different hair dyeing abilities and hair health indices. Therefore, we recommend that hair color shampoos should be used according to the requirements of an individual.

Scalable Three-Dimensional Recording Electrodes for Probing Biological Tissues.

Electrophysiological recording technologies can provide critical insight into the function of the nervous system and other biological tissues. Standard silicon-based probes have limitations, including single-sided recording sites and intrinsic instabilities due to the probe stiffness. Here, we demonstrate high-performance neural recording using double-sided three-dimensional (3D) electrodes integrated in an ultraflexible bioinspired open mesh structure, allowing electrodes to sample fully the 3D interconnected tissue of the brain. In vivo electrophysiological recording using 3D electrodes shows statistically significant increases in the number of neurons per electrode, average spike amplitudes, and signal to noise ratios in comparison to standard two-dimensional electrodes, while achieving stable detection of single-neuron activity over months. The capability of these 3D electrodes is further shown for chronic recording from retinal ganglion cells in mice. This approach opens new opportunities for a comprehensive 3D interrogation, stimulation, and understanding of the complex circuitry of the brain and other electrogenic tissues in live animals over extended time periods.

Emerging Roles of Using Small Extracellular Vesicles as an Anti-Cancer Drug.

Small extracellular vesicles (sEVs) are emerging as a novel therapeutic strategy for cancer therapy. Tumor-cell-derived sEVs contain biomolecules that can be utilized for cancer diagnosis. sEVs can directly exert tumor-killing effects or modulate the tumor microenvironment, leading to anti-cancer effects. In this review, the application of sEVs as a diagnostic tool, drug delivery system, and active pharmaceutical ingredient for cancer therapy will be highlighted. The therapeutic efficacies of sEVs will be compared to conventional immune checkpoint inhibitors. Additionally, this review will provide strategies for sEV engineering to enhance the therapeutic efficacies of sEVs. As a bench-to-bedside application, we will discuss approaches to encourage good-manufacturing-practice-compliant industrial-scale manufacturing and purification of sEVs.

A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer.

OBJECTIVE: High-grade serous ovarian cancer, the most frequent type of ovarian cancer, has a poor prognosis and novel treatments are needed for patients with platinum resistant/refractory disease. New therapeutic strategies targeting cell cycle checkpoints, including CHK1 inhibition with prexasertib, may help improve clinical response and overcome resistance. METHODS: Patients with ovarian cancer (N = 169) were assigned to 4 cohorts as part of the Phase 2 multicenter trial (NCT03414047): Cohort 1: platinum resistant, BRCA-wildtype with ≥3 lines prior therapy; Cohort 2: platinum resistant BRCA-wildtype with <3 lines prior therapy; Cohort 3: platinum resistant, BRCA-mutated with prior PARP inhibitor therapy; Cohort 4: platinum refractory, BRCA-mutated, or BRCA-wildtype with any number of prior therapy lines. The primary endpoint was objective response rate (ORR) and secondary endpoints included disease control rate (DCR), and safety. DNA from tumor biopsies was sequenced to identify biomarkers. RESULTS: The ORR in platinum resistant patients (Cohorts 1--3) was 12.1%, and 6.9% in platinum refractory patients. In platinum resistant patients, DCR was 37.1%, and consistent across cohorts. In platinum refractory patients, DCR was 31.0%. Consistent with the prexasertib mechanism of action, the most common treatment related adverse events of all grades included thrombocytopenia, neutropenia, fatigue, nausea, and anemia. CONCLUSIONS: Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical characteristics, BRCA status, or prior therapies, including PARPi. There was no obvious correlation with genomic alterations in responders vs non-responders, emphasizing the need for alternative biomarker approaches for responder identification.

Cell cycle checkpoints and beyond: Exploiting the ATR/CHK1/WEE1 pathway for the treatment of PARP inhibitor-resistant cancer.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have become a mainstay of therapy in ovarian cancer and other malignancies, including BRCA-mutant breast, prostate, and pancreatic cancers. However, a growing number of patients develop resistance to PARPis, highlighting the need to further understand the mechanisms of PARPi resistance and develop effective treatment strategies. Targeting cell cycle checkpoint protein kinases, e.g., ATR, CHK1, and WEE1, which are upregulated in response to replication stress, represents one such therapeutic approach for PARPi-resistant cancers. Mechanistically, activated cell cycle checkpoints promote cell cycle arrest, replication fork stabilization, and DNA repair, demonstrating the interplay of DNA repair proteins with replication stress in the development of PARPi resistance. Inhibitors of these cell cycle checkpoints are under investigation in PARPi-resistant ovarian and other cancers. In this review, we discuss the cell cycle checkpoints and their roles beyond mere cell cycle regulation as part of the arsenal to overcome PARPi-resistant cancers. We also address the current status and recent advancements as well as limitations of cell cycle checkpoint inhibitors in clinical trials.

All-Tissue-like Multifunctional Optoelectronic Mesh for Deep-Brain Modulation and Mapping.

The development of a multifunctional device that achieves optogenetic neuromodulation and extracellular neural mapping is crucial for understanding neural circuits and treating brain disorders. Although various devices have been explored for this purpose, it is challenging to develop biocompatible optogenetic devices that can seamlessly interface with the brain. Herein, we present a tissue-like optoelectronic mesh with a compact interface that enables not only high spatial and temporal resolutions of optical stimulation but also the sampling of optically evoked neural activities. An in vitro experiment in hydrogel showed efficient light propagation through a freestanding SU-8 waveguide that was integrated with flexible mesh electronics. Additionally, an in vivo implantation of the tissue-like optoelectronic mesh in the brain of a live transgenic mouse enabled the sampling of optically evoked neural signals. Therefore, this multifunctional device can aid the chronic modulation of neural circuits and behavior studies for developing biological and therapeutic applications.

Polarization Control of Deterministic Single-Photon Emitters in Monolayer WSe2.

Single-photon emitters, the basic building blocks of quantum communication and information, have been developed using atomically thin transition metal dichalcogenides (TMDCs). Although the bandgap of TMDCs was spatially engineered in artificially created defects for single-photon emitters, it remains a challenge to precisely align the emitter's dipole moment to optical cavities for the Purcell enhancement. Here, we demonstrate position- and polarization-controlled single-photon emitters in monolayer WSe2. A tensile strain of ∼0.2% was applied to monolayer WSe2 by placing it onto a dielectric rod structure with a nanosized gap. Excitons were localized in the nanogap sites, resulting in the generation of linearly polarized single-photon emission with a g(2) of ∼0.1 at 4 K. Additionally, we measured the abrupt change in polarization of single photons with respect to the nanogap size. Our robust spatial and polarization control of emission provides an efficient way to demonstrate deterministic and scalable single-photon sources by integrating with nanocavities.

Effect of a Wireless Vital Sign Monitoring System on the Rapid Response System in the General Ward.

While wireless vital sign monitoring is expected to reduce the vital sign measurement time (thus reducing the nursing workload), its impact on the rapid response system is unclear. This study compared the time from vital sign measurement to recording and rapid response system activation between wireless and conventional vital sign monitoring in the general ward, to investigate the impact of wireless vital sign monitoring system on the rapid response system. The study divided 249 patients (age > 18 years; female: 47, male: 202) admitted to the general ward into non-wireless (n = 101) and wireless (n = 148) groups. Intervals from vital sign measurement to recording and from vital sign measurement to rapid response system activation were recorded. Effects of wireless system implementation for vital sign measurement on the nursing workload were surveyed in 30 nurses. The interval from vital sign measurement to recording was significantly shorter in the wireless group than in the non-wireless group (4.3 ± 2.9 vs. 44.7 ± 14.4 min, P < 0.001). The interval from vital sign measurement to rapid response system activation was also significantly lesser in the wireless group than in the non-wireless group (27.5 ± 12.9 vs. 41.8 ± 19.6 min, P = 0.029). The nursing workload related to vital sign measurement significantly decreased from 3 ± 0.87 to 2.4 ± 9.7 (P = 0.021) with wireless system implementation. Wireless vital sign monitoring significantly reduced the time to rapid response system activation by shortening the time required to measure the vital signs. It also significantly reduced the nursing workload.