Effects of particle size on toxicity, bioaccumulation, and translocation of zinc oxide nanoparticles to bok choy (Brassica chinensis L.) in garden soil.

The indiscriminate use of zinc oxide nanoparticles (ZnO NPs) in daily life can lead to their release into soil environment. These ZnO NPs can be taken up by crops and translocated to their edible part, potentially causing risks to the ecosystem and human health. In this study, we conducted pot experiments to determine phytotoxicity, bioaccumulation and translocation depending on the size (10 - 30 nm, 80 - 200 nm and 300 nm diameter) and concentration (0, 100, 500 and 1000 mg Zn/kg) of ZnO NPs and Zn ion (Zn2+) in bok choy, a leafy green vegetable crop. After 14 days of exposure, our results showed that large-sized ZnO NPs (i.e., 300 nm) at the highest concentration exhibited greater phytotoxicity, including obstruction of leaf and root weight (42.5 % and 33.8 %, respectively) and reduction of chlorophyll a and b content (50.2 % and 85.2 %, respectively), as well as changes in the activities of oxidative stress responses compared to those of small-sized ZnO NPs, although their translocation ability was relatively lower than that of smaller ones. The translocation factor (TF) values decreased as the size of ZnO NPs increased, with TF values of 0.68 for 10 - 30 nm, 0.55 for 80 - 200 nm, and 0.27 for 300 nm ZnO NPs, all at the highest exposure concentration. Both the results of micro X-ray fluorescence (µ-XRF) spectrometer and bio-transmission electron microscopy (bio-TEM) showed that the Zn elements were mainly localized at the edges of leaves exposed to small-sized ZnO NPs. However, the Zn elements upon exposure to large-sized ZnO NP were primarily observed in the primary veins of leaves in the µ-XRF data, indicating a limitation in their ability to translocate from roots to leaves. This study not only advances our comprehension of the environmental impact of nanotechnology but also holds considerable implications for the future of sustainable agriculture and food safety.

Geographical distribution of the mesozooplankton community in highly productive coastal polynyas of the Ross Sea region marine protected area (RSR MPA) during early summer.

We investigated the recent spatial variation in the mesozooplankton community on the broad shelf of the RSR MPA during the bloom season. The mesozooplankton community was geographically divided into three regions: the Terra Nova Bay polynya, the Ross Sea polynya, and the marginal polynya. Larval euphausiids were dominant in the two polynya regions, whereas copepods were predominant in the marginal polynya region. Salinity, sea ice, and dissolved oxygen related to the different water mass compositions were the most significant factors distinguishing the mesozooplankton community. The key environmental variable separating the three groups was salinity. In accordance with the relatively high mesozooplankton abundance in the polynya regions, the occurrence and size of the polynyas in the December Ross Sea are thought to affect the spatial distribution of mesozooplankton. Consequently, this study indicates that two polynyas in the Ross Sea are vital habitats for krill during summer. Our observation results provide fundamental information for evaluating marine ecosystems and establishing a management plan for the RSR MPA.

Asymmetric allostery in estrogen receptor-α homodimers drives responses to the ensemble of estrogens in the hormonal milieu.

The estrogen receptor-α (ER) is thought to function only as a homodimer but responds to a variety of environmental, metazoan, and therapeutic estrogens at subsaturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations-receptor conformational heterodimers-mimicking the binding of two different ligands. Molecular dynamics simulations showed that the pairs of different ligand poses changed the correlated motion across the dimer interface to generate asymmetric communication between the dimer interface, the ligands, and the surface binding sites for epigenetic regulatory proteins. By examining the binding of the same ligand in crystal structures of ER in the agonist vs. antagonist conformers, we also showed that these allosteric signals are bidirectional. The receptor conformer can drive different ligand binding modes to support agonist vs. antagonist activity profiles, a revision of ligand binding theory that has focused on unidirectional signaling from the ligand to the coregulator binding site. We also observed differences in the allosteric signals between ligand and coregulator binding sites in the monomeric vs. dimeric receptor, and when bound by two different ligands, states that are physiologically relevant. Thus, ER conformational heterodimers integrate two different ligand-regulated activity profiles, representing different modes for ligand-dependent regulation of ER activity.

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model.

Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells.

BACKGROUND: Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models. RESULTS: We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors. Based on drug potency, efficacy, and selectivity, determined through cell viability assays, we focused on two compounds, NB-73 and NB-115 (NB compounds), for further investigation. NB compounds potently and selectively inhibited FOXM1 with lesser effects on other FOX family members. NB compounds decreased FOXM1 expression via targeting the FOXM1 protein by promoting its proteasome-mediated degradation, and effectively suppressed FOXM1 gene targets at both the protein and mRNA level. At the cellular level, NB compounds promoted apoptotic cell death. Importantly, while inhibition of apoptosis using a pan-caspase inhibitor rescued HGSOC cells from NB compound-induced cell death, it did not rescue FOXM1 protein degradation, supporting that FOXM1 protein loss from NB compound treatment is specific and not a general consequence of cytotoxicity. Drug washout studies indicated that FOXM1 reduction was retained for at least 72 h post-treatment, suggesting that NB compounds exhibit long-lasting effects in HGSOC cells. NB compounds effectively suppressed both two-dimensional and three-dimensional HGSOC cell colony formation at sub-micromolar concentrations. Finally, NB compounds exhibited synergistic activity with carboplatin in HGSOC cells. CONCLUSIONS: NB compounds are potent, selective, and efficacious inhibitors of FOXM1 in HGSOC cells and are worthy of further investigation as HGSOC therapeutics.

The complete mitochondrial genome of the ice krill Euphausia crystallorophias Holt & Tattersall, 1906 (Euphausiacea, Euphausiidae), from the Ross Sea, Antarctica.

The mitogenome of Euphausia crystallorophias collected from the Ross Sea Region Marine Protected Area (RSR MPA) is described for the first time. The assembled mitogenome was 17,291 bp in length and consisted of two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and noncoding regions, all of which were identical to those of other euphausiid species. The most common start codon for the 13 PCGs was ATG, and the most common termination codon was TAA. The overall G + C content was 33.2% in the heavy strand. Euphausia crystallorophias was sister to E. superba in the phylogenetic analysis. The mitogenome of E. crystallorophias provided significant DNA molecular data for further identification and phylogenetic analysis within the euphausiids.

Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

Asymmetric Allostery in Estrogen Receptor-α Homodimers Drives Responses to the Ensemble of Estrogens in the Hormonal Milieu.

The estrogen receptor-α (ER) is thought to function only as a homodimer, but responds to a variety of environmental, metazoan, and therapeutic estrogens at sub-saturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations -receptor conformational heterodimers-mimicking the binding of two different ligands. Molecular dynamics simulations showed that the pairs of different ligand poses changed the correlated motion across the dimer interface to generate asymmetric communication between the dimer interface, the ligands, and the surface binding sites for epigenetic regulatory proteins. By examining binding of the same ligand in crystal structures of ER in the agonist versus antagonist conformers, we also showed that these allosteric signals are bidirectional. The receptor conformer can drive different ligand binding modes to support agonist versus antagonist activity profiles, a revision of ligand binding theory that has focused on unidirectional signaling from ligand to the coregulator binding site. We also observed differences in the allosteric signals between ligand and coregulator binding sites in the monomeric versus dimeric receptor, and when bound by two different ligands, states that are physiologically relevant. Thus, ER conformational heterodimers integrate two different ligand-regulated activity profiles, representing new modes for ligand-dependent regulation of ER activity. Significance: The estrogen receptor-α (ER) regulates transcription in response to a hormonal milieu that includes low levels of estradiol, a variety of environmental estrogens, as well as ER antagonists such as breast cancer anti-hormonal therapies. While ER has been studied as a homodimer, the variety of ligand and receptor concentrations in different tissues means that the receptor can be occupied with two different ligands, with only one ligand in the dimer, or as a monomer. Here, we use X-ray crystallography and molecular dynamics simulations to reveal a new mode for ligand regulation of ER activity whereby sequence-identical homodimers can act as functional or conformational heterodimers having unique signaling characteristics, with ligand-selective allostery operating across the dimer interface integrating two different signaling outcomes.

Parkin Enhances Gefitinib-induced Anoikis in HeLa Cervical Cancer Cells.

BACKGROUND/AIM: Gefitinib exhibits anticancer activity against cervical cancer cells via anoikis, a type of apoptosis induced by cell detachment from the extracellular matrix. Previous studies have reported that Parkin expression affects the efficacy of anticancer drugs. However, the impact of Parkin expression on the therapeutic effects of gefitinib in human cervical cancer remains unclear. Thus, this study aimed to evaluate whether Parkin over-expression improves the therapeutic effects of gefitinib against HeLa cervical cancer cells. MATERIALS AND METHODS: Cell viability and apoptotic death of HeLa cells were measured by trypan blue dye exclusion assay and flow cytometry. Cell detachment, adhesion, spreading, and cell-cell interaction were observed by inverted microscopy. Alteration of adhesion-related molecules was evaluated by confocal microscopy and western blot assay. RESULTS: Parkin expression potentiated gefitinib-induced cell detachment by affecting the organization of the actin cytoskeleton. In addition, Parkin expression induced a further reduction in the reattachment of and interaction between detached cells. The therapeutic efficacy of low-dose gefitinib combined with Parkin expression was equivalent to that of high-dose gefitinib alone. CONCLUSION: Parkin expression promotes gefitinib-induced anoikis, consequently increasing the efficacy of gefitinib against HeLa human cervical cancer cells. Based on our results, we propose that Parkin can be used to increase the anti-cancer effect of gefitinib on cervical cancer cells.

Apoptotic Effect of Isoimpertorin via Inhibition of c-Myc and SIRT1 Signaling Axis.

Though Isoimperatorin from Angelicae dahuricae is known to have antiviral, antidiabetic, anti-inflammatory and antitumor effects, its underlying antitumor mechanism remains elusive so far. Hence, the apoptotic mechanism of Isoimperatorin was explored in hepatocellular carcinomas (HCCs). In this study, Isoimperatorin inhibited the viability of Huh7 and Hep3B HCCs and increased the subG1 apoptotic portion and also abrogated the expression of pro-poly-ADP ribose polymerase (pro-PARP) and pro-caspase 3 in Huh7 and Hep3B cells. Also, Isoimperatorin abrogated the expression of cyclin D1, cyclin E1, CDK2, CDK4, CDK6 and increased p21 as G1 phase arrest-related proteins in Huh7 and Hep3B cells. Interestingly, Isoimperatorin reduced the expression and binding of c-Myc and Sirtuin 1 (SIRT1) by Immunoprecipitation (IP), with a binding score of 0.884 in Huh7 cells. Furthermore, Isoimperatorin suppressed the overexpression of c-Myc by the proteasome inhibitor MG132 and also disturbed cycloheximide-treated c-Myc stability in Huh7 cells. Overall, these findings support the novel evidence that the pivotal role of c-Myc and SIRT1 is critically involved in Isoimperatorin-induced apoptosis in HCCs as potent molecular targets in liver cancer therapy.

Correlations between heart sound components and hemodynamic variables.

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Effect of dexmedetomidine on the incidence of postoperative acute kidney injury in living donor liver transplantation recipients: A randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications after living-donor liver transplantation (LDLT) that has great impact on recipient and graft outcomes. Dexmedetomidine is reported to decrease the incidence of AKI. In the current study, we investigated whether intraoperative dexmedetomidine infusion would reduce the AKI following LDLT. MATERIAL AND METHODS: In total, 205 adult patients undergoing elective LDLT were randomly assigned to the dexmedetomidine group (n=103) or the control group (n=102). Dexmedetomidine group received continuous dexmedetomidine infusion at a rate of 0.4 mcgÖ¼/kg/hr after the anesthesia induction until 2 hours after graft reperfusion. The primary outcome was to compare the incidence of AKI. Secondary outcomes included serial lactate levels during surgery, chronic kidney disease, major adverse cardiovascular events, early allograft dysfunction, graft failure, overall mortality, duration of mechanical ventilation, ICU and hospital length of stay. Intraoperative hemodynamic parameters were also collected. RESULTS: Of 205 recipients, 42.4% (n=87) developed AKI. The incidence of AKI was lower in the dexmedetomidine group (35.0%, n=36/103) compared with the control (50.0%, n=51/102) ( P =0.042). There were significantly lower lactate levels in the dexmedetomidine group after reperfusion (4.39 [3.99-4.8] vs 5.02 [4.62-5.42], P =0.031) until the end of surgery (4.23 [3.73-4.73] vs 5.35 [4.84-5.85], P =0.002). There were no significant differences in the other secondary outcomes besides lactate. Also, intraoperative mean blood pressure, cardiac output, and systemic vascular resistance did not show any difference. CONCLUSION: Our study suggests that intraoperative dexmedetomidine administration was associated with significantly decreased AKI incidence and lower intraoperative serum lactate levels in LDLT recipients, without untoward hemodynamic effects.

Three polymorphs of a new N,N'-dipropylated isoindigo derivative.

A newly synthesized N,N'-dipropyl-substituted isoindigo derivative, namely, 1-propyl-3-(1-propyl-1,2-dihydro-2-oxo-3H-indol-3-ylidene)-1,3-dihydro-2H-indol-2-one, C22H22N2O2, was found to have three polymorphic forms (denoted Forms I, II and III) under various crystallization conditions. Crystal structure analysis indicated that Form III had a significantly different molecular conformation from the other two polymorphs. Their different packing arrangements were correlated with differences in the intermolecular interactions. Thermal measurements revealed that Forms I and II are enantiotropically related, and Form II exhibits thermally dynamic behaviour.

Human Fibroblast-Derived Matrix Hydrogel Accelerates Regenerative Wound Remodeling Through the Interactions with Macrophages.

Herein, a novel extracellular matrix (ECM) hydrogel is proposed fabricated solely from decellularized, human fibroblast-derived matrix (FDM) toward advanced wound healing. This FDM-gel is physically very stable and viscoelastic, while preserving the natural ECM diversity and various bioactive factors. Subcutaneously transplanted FDM-gel provided a permissive environment for innate immune cells infiltration. Compared to collagen hydrogel, excellent wound healing indications of FDM-gel treated in the full-thickness wounds are noticed, particularly hair follicle formation via highly upregulated ß-catenin. Sequential analysis of the regenerated wound tissues disclosed that FDM-gel significantly alleviated pro-inflammatory cytokine and promoted M2-like macrophages, along with significantly elevated vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) level. A mechanistic study demonstrated that macrophages-FDM interactions through cell surface integrins α5ß1 and α1ß1 resulted in significant production of VEGF and bFGF, increased Akt phosphorylation, and upregulated matrix metalloproteinase-9 activity. Interestingly, blocking such interactions using specific inhibitors (ATN161 for α5ß1 and obtustatin for α1ß1) negatively affected those pro-healing growth factors secretion. Macrophages depletion animal model significantly attenuated the healing effect of FDM-gel. This study demonstrates that the FDM-gel is an excellent immunomodulatory material that is permissive for host cells infiltration, resorbable with time, and interactive with macrophages, where it thus enables regenerative matrix remodeling toward a complete wound healing.

Prognostic Value of Mitral Annular Calcification in Liver Transplant Patients: Implication in Posttransplant Outcomes.

BACKGROUND: With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes. METHODS: We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality. RESULTS: MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d (P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC (P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT. CONCLUSIONS: The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.

Astragalus membranaceus Extract Induces Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Heat Shock Protein 27 and Androgen Receptor in Prostate Cancers.

Although Astragalus membranaceus is known to have anti-inflammatory, anti-obesity, and anti-oxidant properties, the underlying apoptotic mechanism of Astragalus membranaceus extract has never been elucidated in prostate cancer. In this paper, the apoptotic mechanism of a water extract from the dried root of Astragalus membranaceus (WAM) was investigated in prostate cancer cells in association with heat shock protein 27 (HSP27)/androgen receptor (AR) signaling. WAM increased cytotoxicity and the sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and cysteine aspartyl-specific protease 3 (caspase 3), and attenuated the expression of B-cell lymphoma 2 (Bcl-2) in LNCaP cells after 24 h of exposure. Consistently, WAM significantly increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive LNCaP cells. WAM decreased the phosphorylation of HSP27 on Ser82 and inhibited the expression of the AR and prostate-specific antigen (PSA), along with reducing the nuclear translocation of p-HSP27 and the AR via the disturbed binding of p-HSP27 with the AR in LNCaP cells. WAM consistently inhibited the expression of the AR and PSA in dihydrotestosterone (DHT)-treated LNCaP cells. WAM also suppressed AR stability, both in the presence and absence of cycloheximide, in LNCaP cells. Taken together, these findings provide evidence that WAM induces apoptosis via the inhibition of HSP27/AR signaling in prostate cancer cells and is a potent anticancer candidate for prostate cancer treatment.

Safety and Clinical Outcomes of Two-Session Catheter-Directed Sclerotherapy Using Ethanol for Endometrioma.

PURPOSE: To evaluate the safety and clinical outcome of two-session catheter-directed sclerotherapy (CDS) with 99% ethanol in patients with endometrioma. MATERIALS AND METHODS: This prospective study was approved by the institutional review board with written informed consent obtained from all participants and was registered on clinicaltrial.gov. Consecutive patients with ovarian endometrioma between June 2020 and March 2023 were prospectively evaluated for two sessions of CDS. After successful transvaginal ultrasound-guided puncture of the endometrioma, the biopsy needle was exchanged for a 7- or 8.5-F catheter for aspiration and ethanol injection. The catheter was retained in situ for a second session the next day. Endometrioma volume was measured on ultrasound before and 1, 3, and 6 months after CDS, and volume reduction ratio (VRR) was calculated. Serum anti-Müllerian hormone (AMH) was measured before and 6 months after CDS to assess ovarian reserve. RESULTS: Thirty-one endometriomas in 22 patients (mean age, 31.0 years; range, 19-44 years) were treated; 28 endometriomas were successfully treated with two-session CDS, while one session was incomplete in three endometriomas in three patients due to contrast medium leakage or pain. Minor procedure-related complications developed in four patients and resolved spontaneously before discharge on the same day of the second session. No recurrence was identified during follow-up. At the 6-month follow-up, the mean endometrioma diameter decreased from 5.5 ± 1.7 to 1.4 ± 0.9 cm (P < 0.001), and the serum AMH level was lowered without statistical significance (1.37 ± 0.96 ng/mL vs. 1.18 ± 0.92 ng/mL; P = 0.170). VRRs at 1, 3, and 6 months after CDS were 84.3 ± 13.7%, 94.3 ± 5.8%, and 96.4 ± 4.7%, respectively. CONCLUSION: Two-session CDS with 99% ethanol is safe, feasible, and effective for treating endometrioma with the ovarian function well preserved.

Impact of exercise training and diet therapy on the physical fitness, quality of life, and immune response of people living with HIV/AIDS: a randomized controlled trial.

BACKGROUND: Exercise and dietary nutrition are considered crucial in human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) treatment protocols and people living with HIV/AIDS (PLWHA) rehabilitation care. However, there is no well-studied research evaluating the effects of combined interventions on the fitness and immune systems of PLWHA. Therefore, this study aimed to analyze the effects of exercise and dietary intervention on physical fitness, quality of life and immune response in PLWHA. METHODS: This was an experimental study, with a sample of 25 male PLWHA divided into two groups: the intervention group (IG: 12 participants) and the control group (CG: 13 participants). All participants have not had any exercise habits and nutritional supplements in the past six months. The participants in the IG completed 45 min of exercise (60-80% HRmax) 4 times per week for 4 weeks. The exercise was in the form of brisk walking or running. They were also given a nutritional dietary supplement 3 times a day for 4 weeks. The 13 individuals in the CG continued their normal daily life (physical activity and diet). The following parameters were evaluated before and after the intervention: body composition, physical fitness, immune response, quality of life (QoL), stress, dietary behavior, dietary habits, exercise motivation, and physical self-efficacy. RESULTS: The significant changes were observed in burnout of stress variables and physical efficiency index (PEI) of physical fitness in the IG (p =.023). Moreover, in the saliva samples, sal-T levels significantly increased only after the intervention in the IG (p =.012). Additionally, regarding the analysis of the interaction (group × time), there was a significant improvement in the reaction speed (p =.001) and grip strength (left: p =.002, right: p =.030) and a significant difference in physical satisfaction in QoL (p =.001), stress burnout (p =.043), self-confidence in physical efficacy (p =.045), external display (p =.008), and fulfillment (p =.047) in exercise motivation. Moreover, the significant effect of the intervention on emotional eating in dietary behavior was shown in the comparison of the IG before and after intervention (p =.001) and in the comparison of the IG group with the CG after the experiment (p =.013). However, there was no significant effect of time or interaction between the condition and time on body composition. CONCLUSIONS: In conclusion, exercise training and diet therapy caused changes in physical fitness and Sal-T levels, which had positive effects on the health promotion of PLWHA.

Meta-Analysis of Studies on the Effects of Digital Therapeutics.

Digital therapeutics (DTx), novel treatment methods that have the potential to surpass traditional approaches such as pills, have received considerable research attention. Various efforts have been made to explore effective treatment methods that actively integrate DTx. This review investigates DTx treatment outcomes comprehensively through a meta-analysis. The analysis-a manual search of studies on "digital therapeutics"-includes DTx studies from January 2017 to October 2022. Hedges' g is used to quantify effect size for fifteen studies analyzed, encompassing eight control groups. Further, a quality assessment is performed using the Bias Risk Assessment Tool. The Hedges' g analysis results provide weighted average effect sizes across the eight control groups, revealing a substantial value of 0.91 (95% CI: 0.62 to 1.20); this signifies a moderate to large effect size. Further refinement, which excludes one study, yields an increased weighted average effect size of 1.13 (95% CI: 0.91 to 1.36). The quality assessment results consistently indicate a low risk of bias across studies. The meta-analysis results indicate that DTx can provide significant pivotal therapeutic impacts and offer a means to personalize treatment approaches and streamline the management of patients' treatment processes.

Gefitinib induces anoikis in cervical cancer cells.

Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin ß1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer. [BMB Reports 2024; 57(2): 104-109].