Assessment of Osteoporosis at the Lumbar Spine Using Ultrashort Echo Time Magnetization Transfer (UTE-MT) MRI.

BACKGROUND: Bone collagen-matrix contributes to the mechanical properties of bone by imparting tensile strength and elasticity, which can be indirectly quantified by ultrashort echo time magnetization transfer ratio (UTE-MTR) to assess osteoporosis. PURPOSE: To evaluate osteoporosis at the human lumbar spine using UTE-MTR. STUDY TYPE: Prospective. POPULATION: One hundred forty-eight-volunteers (age-range, 50-85; females, N = 90), including 81-normal bone density, 35-osteopenic, and 32-osteoporotic subjects. Ten additional healthy volunteers were recruited to study the intrasession reproducibility of the UTE-MT. FIELD STRENGTH/SEQUENCE: 3T/UTE-MT, short repetition-time adiabatic inversion recovery prepared UTE (STAIR-UTE), and iterative decomposition of water-and-fat with echo-asymmetry and least-squares estimation (IDEAL-IQ). ASSESSMENT: Fracture risk was calculated using Fracture-Risk-Assessment-Tool (FRAX). Region-of-interests (ROIs) were delineated on the trabecular area in the maps of bone-mineral-density, UTE-MTR, collagen-bound water proton-fraction (CBWPF), and bone-marrow fat fraction (BMFF). STATISTICAL TESTS: Linear-regression and Bland-Altman analysis were performed to assess the reproducibility of UTE-MTR measurements in the different scans. UTE-MTR and BMFF were correlated with bone-mineral-density using Pearson's regression and with FRAX scores using nonlinear regression. The abilities of UTE-MTR, CBWPF, and BMFF to discriminate between the three patient subgroups were evaluated using receiver-operator-characteristic (ROC) analysis and area-under-the-curve (AUC). Decision-curve-analysis (DCA) and clinical-impact curves were used to evaluate the value of UTE-MTR in clinical diagnosis. The DeLong test was used to compare the ROC curves. P-value <0.05 was considered statistically significant. RESULTS: Excellent reproducibility was obtained for the UTE-MT measurements. UTE-MTR strongly correlated with bone-mineral-density (r = 0.76) and FRAX scores (r = -0.77). UTE-MTR exhibited higher AUCs (≥0.723) than BMFF, indicating its superior ability to distinguish between the three patient subgroups. The DCA and clinical-impact curves confirmed the diagnostic value of UTE-MTR. UTE-MTR and CBWPF showed similar performance in correlation with bone-mineral-density and cohort classification. DATA CONCLUSION: UTE-MTR strongly correlates with bone-mineral-density and FRAX and shows great potential in distinguishing between normal, osteopenic, and osteoporotic subjects. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Targeting histone deacetylase 1 (HDAC1) in the bone marrow stromal cells revers imatinib resistance by modulating IL-6 in Ph + acute lymphoblastic leukemia.

Bone marrow stromal cells (BMSCs) can promote the growth of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Histone deacetylases (HDACs) play essential roles in the proliferation and apoptosis resistance of Ph + ALL cells. In our previous study, inhibiting histone deacetylase 1 (HDAC1) decreases the proliferation of Ph + ALL cells. However, little is known regarding how HDAC1 in BMSCs of Ph + ALL patients affects the imatinib (IM) resistance. Therefore, the present work examined the roles of HDAC1 in BMSCs. Overexpression of HDAC1 was found in BMSCs of Ph + ALL patients with IM resistance. In addition, the Ph + ALL cell line SUP-B15 was co-cultured with BMSCs after lentivirus transfection for regulating HDAC1 expression. Knockdown of HDAC1 within BMSCs elevated the IM-mediated SUP-B15 cell apoptosis, while increasing HDAC1 expression had an opposite effect. IL-6 in BMSCs, which is an important factor for the microenvironment-associated chemoresistance, showed evident up-regulation in HDAC1-upregulated BMSCs and down-regulation in HDAC1-downregulated BMSCs. While recombinant IL-6 (rIL-6) can reversed the sensitivity of SUP-B15 cells to IM induced by downregulating HDAC1 expression in BMSCs. HDAC1 showed positive regulation on IL-6 transcription and secretion. Moreover, IL-6 secretion induced by HDAC1 in BMSCs might enhance IM resistance in Ph + ALL cells. With regard to the underlying molecular mechanism, NF-κB, an important signal responsible for IL-6 transcription in BMSCs, mediated the HDAC1-regulated IL-6 expression. Collectively, this study facilitated to develop HDAC1 inhibitors based not only the corresponding direct anti-Ph + ALL activity but also the regulation of bone marrow microenvironment.

Association between choroidopathy and photoreceptors during the early stage of diabetic retinopathy: a cross-sectional study.

PURPOSE: To explore the role of choroidopathy in diabetic retinopathy (DR) by investigating the correlation between alterations of choroidal vessel and photoreceptors during the early stage of DR. METHODS: We performed a cross-sectional comparison of diabetic patients without DR (NDR group; n=16) and those with mild nonproliferative diabetic retinopathy (NPDR group; n=39). Optical coherence tomography (OCT) images of choroidal vessel alterations and photoreceptor structures were evaluated using the choroidal vascularity index (CVI) and adjusted ellipsoid zone (EZ) reflectivity, respectively. To evaluate the function of cone photoreceptors, the fundamental, harmonic amplitudes, the parameters S and Rmp3 were calculated from the electroretinogram (ERG). These factors were compared between groups. The correlation between the CVI and parameters describing the function and structure of the photoreceptors was evaluated. RESULTS: The significant decrease was observed in the CVI in the NPDR group compared to the NDR group (0.67 ± 0.04 vs. 0.70 ± 0.06; p = 0.028), but not in the adjusted EZ reflectivity or ERG parameters. In NPDR group and merging the 2 groups, CVI was moderately positively correlated with the fundamental amplitude obtained by the flicker ERG (NPDR only: r = 0.506; p = 0.001; merge the 2 groups: r = 0.423; p = 0.001), which was regulated by the response of the cone photoreceptors. The CVI was positively and moderately correlated with the logS (NPDR only: r = 0.462; p = 0.003; merge the 2 groups: r = 0.355; p = 0.008), indicating the sensitivity of cone cell light transduction. CONCLUSION: Compared to eyes without DR, CVI decreased representing choroidal vascular changes in eyes with mild NPDR. These changes may be related to the functional impairment of cone photoreceptors, especially phototransduction sensitivity, as the DR develops.

[Analysis of Prenatal Ultrasound Manifestations in 15 Cases of Cantrell Syndrome]. / Cantrell综合征15ä¾‹äº§å‰è¶ å£°è¡¨çŽ°åˆ†æž.

Objective: Cantrell syndrome, a rare congenital disorder, is characterized by a unique collection of defects on the midline abdominal wall, the lower sternum, the anterior diaphragm, and the diaphragmatic pericardium in addition to some form of intracardiac defect. So far, most of the reports on fetuses with Cantrell syndrome worldwide are either case reports or literature reviews, and few comprehensive studies on fetuses with Cantrell syndrome have been reported, especially in domestic literature. This study aims to provide a detailed analysis of 15 cases of Cantrell syndrome fetuses, focusing on their prenatal ultrasound manifestations and postnatal examination outcomes. Methods: A retrospective analysis was conducted with 15 cases of fetuses diagnosed with Cantrell syndrome via prenatal ultrasound examinations between March 2018 and July 2023. Ultrasound examinations were performed in accordance with the Guidelines for Obstetric Ultrasound in China, including first-trimester fetal ultrasound scan and routine second-trimester fetal ultrasound scan. Gestational age was evaluated and nuchal translucency (NT) was measured during first-trimester fetal ultrasound scan at 11 to 13+6 weeks. The diagnostic criterion for NT thickening was NT≥3.0 mm and the screening of severe fetal structural malformations was performed, including the screening of the head, the neck, the thorax, the abdominal content, the abdominal wall, the limbs and other structures. During routine second-trimester fetal ultrasound scan, the fetal biometry was assessed and an anatomy survey was performed. Post-induction and postnatal outcomes of fetuses diagnosed with Cantrell syndrome by prenatal ultrasound were followed up by postnatal observation, inquiries with the electronic medical record system, or telephone follow-up. The prenatal ultrasound imaging manifestations and features of the fetuses with Cantrell syndrome, as well as their post-induction or postnatal examination results were comprehensively summarized and analyzed. Results: The study involved pregnant women of the average age of 30.1±3.5 years, with ultrasound diagnoses made between 11 to 26 weeks of gestation (mean: 13.4±4.0 weeks). Among the 15 cases, there were 10 singleton pregnancies and 5 cases of one twin in a pair of twins. These twins comprised 3 monochorionic diamniotic twins and 2 dichorionic diamniotic twins, with Cantrell syndrome present in one of the twins in all 5 cases. Thirteen cases were diagnosed by fetal ultrasound scan conducted in the first trimester, with 10 being singleton pregnancies and 3 being twin pregnancies (1 monochorionic diamniotic twins and 2 dichorionic diamniotic twins). One case was missed in the first-trimester ultrasound scan, resulting in a missed diagnosis rate of 7.1%. Two cases were diagnosed in second-trimester fetal ultrasound scan, both involving monochorionic diamniotic twins. One case was a referral from another hospital at 19 weeks, while the other was initially not diagnosed for Cantrell syndrome and was diagnosed at 26 weeks. Prenatal ultrasound examinations revealed a consistent pattern of abnormalities across all 15 fetuses, including manifestations of ectopic cordis combined with abdominal protrusion mass. Specifically, 4 cases were diagnosed with omphalocele, 4 with gastroschisis, and the remaining 7 had uncertain coverage of the membrane on the surface of the abdominal protrusion mass. Six fetuses had complete ectopic cordis, while nine had partial ectopic cordis. Fetal echocardiography was performed in 5 cases, revealing intracardiac malformations in 4 cases (80%). Notably, 2 cases were diagnosed in the second trimester, including one with right ventricular hypoplasia accompanied by interventricular septal defect and another with double outlet right ventricle accompanied by interventricular septal defect. Additionally, 2 cases were diagnosed in the first trimester, one with single atrium and single ventricle, and the other with complete transposition of the great arteries. Of the 15 cases of fetuses with Cantrell syndrome, 13 (86.7%) exhibited concomitant malformations in other systems. These included 7 cases of spinal malformations, 4 limb abnormalities, 3 umbilical cord abnormalities, 2 central nervous system malformations, 1 facial malformation, and 2 fetal hydrops. Spinal malformations were the most prevalent concomitant malformation, accounting for 46.7% of all cases. Among the 14 fetuses undergoing NT examination, 7 (50%) had increased NT, and 5 of them had cystic hygroma. All 10 singleton pregnancies underwent induced abortion, and the appearance of the induced fetuses was consistent with the prenatal ultrasound manifestations. In the twin pregnancies, 2 cases experienced intrauterine fetal death, while 2 underwent selective reduction. Notably, 3 of these cases exhibited postnatal appearances consistent with prenatal ultrasound manifestation, while 1 case showed an indistinct appearance after selective reduction during delivery. One case was lost to follow-up. Genetic testing was conducted for 4 induced fetuses, none of which yielded any relevant pathogenic or potentially pathogenic variants. Conclusion: In conclusion, Cantrell syndrome manifests prenatally with ectopic cordis combined with abdominal protrusion mass, often accompanied by intracardiac malformations and other concomitant malformations. While most cases can be diagnosed in the first trimester, there remains the possibility of missed diagnoses, which underscores the importance of close follow-up in the second trimester.

KRT18 regulates trophoblast cell migration and invasion which are essential for embryo implantation.

Female infertility is a worldwide concern that impacts the quality of life and well-being of affected couples. Failure of embryo implantation is a major cause of early pregnancy loss and is precisely regulated by a programmed molecular mechanism. Recent studies have shown that proper trophoblast adhesion and invasion are essential for embryo implantation. However, the potential regulatory mechanism involved in trophoblast adhesion and invasion has yet to be fully elucidated. KRT18 has been reported to play a critical role in early embryonic development, but its physiological function in embryo implantation remains unclear. In the present study, we revealed that KRT18 was highly expressed in trophoblast cells and that knockdown of KRT18 in mouse embryos inhibited embryo adhesion and implantation. In vitro experiments further showed that silencing KRT18 disturbed trophoblast migration and invasion. More importantly, we provide evidence that KRT18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells through microscale thermophoresis (MST) analysis and molecular biology experiments. In brief, our data reveal that KRT18, which is highly expressed in trophoblast cells, plays an important role in the regulation of trophoblast invasion and adhesion during embryo implantation by directly binding to E-cadherin.

Impaired immune responses and prolonged viral replication in lung allograft recipients infected with SARS-CoV-2 in the early phase after transplantation.

PURPOSE: Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. METHODS: We investigated patients who were infected with SARS-CoV-2 in the early phase (18-103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. RESULTS: One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. CONCLUSION: Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post-LuTx, and in case of infection treated generously with currently available interventions.

The action logic of the older adults about health-seeking in South Rural China.

BACKGROUND: The Chinese government has invested significant resources to build many rural healthcare stations. However, in the face of convenient medical paths and accessible medical resources, the utilization rate of health services for older adults in rural areas is surprisingly low. This study explored why health-seeking behavior among older adults in rural China was not active. METHODS: Data were collected through participatory rural appraisal (PRA) with 108 participants in 12 villages in southern China. Daily schedule and social and resource mapping were employed to outline the range of activities and the routine of the older adults, as well as in-depth interviews to understand the logic of their healthcare choices. Data collected were analyzed by content analysis. RESULTS: Three themes were generated: (1) perceptions of health status (being healthy or sick): the rural older adults used the ability to handle routine chores as a measure of health status; (2) prioritization of solving symptoms over curing diseases: the older adults preferred the informal self-medication to cope with diseases, as long as there were no symptoms and no pain; (3) 'unpredictable' troubles: they tended to favor the 'optimal' solution of keeping their lives in order rather than the best medical treatment options. CONCLUSION: This study showed that the medical practices of the rural elderly were profoundly influenced by their perceptions of health and their life experiences. In the face of diseases, they tended to keep their lives in order, preferring self-treatment practices that address symptoms or selectively following medical advice rather than medical and science-based clinical solutions. In the future, the construction of rural health care should focus on changing the 'inaccessibility' of healthcare resources at the subjective level of the rural elderly and develop culturally adaptable health education.

Protein-Crowned Micelles for Targeted and Synergistic Tumor-Associated Macrophage Reprogramming to Enhance Cancer Treatment.

Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancers, but achieving multitarget therapy of TAMs is still challenging. Here, we develop a protein-crowned micelle system for targeted and synergistic TAM reprogramming to enhance cancer treatment. The doxorubicin-loaded micelles with a hemoglobin crown (Hb-DOXM) can bind with endogenous plasma haptoglobin to realize specific M2-type TAM targeting. Under the tumor hypoxic and acidic environments, Hb-DOXM can responsively release O2 and DOX to reduce the recruitment of TAMs by hypoxia remission and release DOX to kill M2-type TAMs and cancer cells. To reprogram TAMs adequately, the TAM-modulating drug celecoxib is further encapsulated (Hb-DOXM@Cel) to repolarize M2-type TAMs. The targeted and synergistic TAM reprogramming by Hb-DOXM@Cel can remodel the tumor microenvironment (TME) to an immunostimulatory microenvironment and augment the antitumor effect of cytotoxic T lymphocyte, thus strongly enhancing the DOX-based chemotherapy. The protein-crowned micelle strategy presents a targeted and synergistic TAM therapy tool for enhanced cancer treatment.

The efficacy of low-frequency ultrasound as an added treatment for chronic wounds: A meta-analysis.

We performed a meta-analysis to evaluate the effect of low-frequency ultrasound as an added treatment for chronic wounds. A systematic literature search up to May 2022 was performed and 838 subjects with chronic wounds at the baseline of the studies; 412 of them were using the low-frequency ultrasound (225 low-frequency high-intensity contact ultrasound for diabetic foot wound ulcers, and 187 low-frequency low-intensity non-contact ultrasound for a venous leg wound ulcers), and 426 were using standard care (233 sharp debridements for diabetic foot wound ulcers and 193 sham treatments for venous leg wound ulcers). Odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of low-frequency ultrasound as an added treatment for chronic wounds using the dichotomous, and contentious methods with a random or fixed-effect model. The low-frequency high-intensity contact ultrasound for diabetic foot wound ulcers had significantly lower non-healed diabetic foot wound ulcers at ≥3 months (OR, 0.37; 95% CI, 0.24-0.56, P < .001), a higher percentage of diabetic foot wound ulcers area reduction (MD, 17.18; 95% CI, 6.62-27.85, P = .002) compared with sharp debridement for diabetic foot wound ulcers. The low-frequency low-intensity non-contact ultrasound for a venous leg wound ulcers had a significantly lower non-healed venous leg wound ulcers at ≥3 months (OR, 0.31; 95% CI, 0.15-0.62, P = .001), and higher percentage venous leg wound ulcers area reduction (MD, 18.96; 95% CI, 2.36-35.57, P = .03) compared with sham treatments for a venous leg wound ulcers. The low-frequency ultrasound as an added treatment for diabetic foot wound ulcers and venous leg wound ulcers had significantly lower non-healed chronic wound ulcers at ≥3 months, a higher percentage of chronic wound ulcers area reduction compared with standard care. The analysis of outcomes should be with caution because of the low sample size of all the 17 studies in the meta-analysis and a low number of studies in certain comparisons.

PHD2 attenuates high-glucose-induced blood retinal barrier breakdown in human retinal microvascular endothelial cells by regulating the Hif-1α/VEGF pathway.

OBJECTIVE: Diabetic macular edema (DME) is one of the most frequent causes of severe vision loss. The pathogenesis of DME is still not fully understood; however, it is hypothesized to result from breakdown of the blood-retinal barrier (BRB) due to retinal inflammation by vascular endothelial growth factor (VEGF) secretion under hyperglycemic conditions. In this investigation, we discovered that Prolyl-4-hydroxylase 2 (PHD2), an upstream regulator of hypoxia-inducible factor 1 (HIF-1) modulates VEGF expression and thus preserves BRB function in the mouse retina. MATERIALS AND METHODS: Primary human retinal microvascular endothelial cells (hRMECs) were cultured in human endothelial serum-free growth medium and exposed to hyperglycemia. Changes in cell viability were investigated by an MTT assay. BRB function in each group was revealed by a paracellular permeability assay and trans-endothelial electrical resistance (TEER). Morphological changes in the BRB were investigated by immunofluorescence staining of occludin and zonula occludens-1 (ZO-1). The mRNA and protein levels of the tight junction proteins, PHD2, HIF-1α, and VEGF were measured by reverse transcription-quantitative PCR (RT-qPCR), western blot analysis and ELISA. RESULTS: Under hyperglycemic conditions, the viability of hRMECs was decreased, and PHD2 expression was downregulated, accompanied by increased paracellular permeability and decreased trans-endothelial electrical resistance. Additionally, HIF-1α and VEGF expression levels were increased, whereas the expression levels of tight junction proteins, including occludin and ZO-1, were decreased and BRB function was compromised. The PHD2 activator R59949 (diacylglycerol kinase inhibitor II), altered these pathological changes, and the PHD2 inhibitor dimethyloxalylglycine (DMOG) resulted in the opposite effects. CONCLUSION: These results demonstrated that PHD2 inhibited HIF-1 activity by inhibiting HIF-1α expression in hRMECs under hyperglycemic conditions, which led to the downregulation of the expression of the angiogenic factor VEGF, and thus helped to maintain the functions of hRMECs. Therefore, it is reasonable to propose that PHD2 could be a potential novel target for the treatment of DME or other diseases with a similar pathogenesis.

Melatonin prevents experimental central serous chorioretinopathy in rats.

Central serous chorioretinopathy (CSC) is a vision-threatening disease with no validated treatment and unclear pathogenesis. It is characterized by dilation and leakage of choroidal vasculature, resulting in the accumulation of subretinal fluid, and serous detachment of the neurosensory retina. Numerous studies have demonstrated that melatonin had multiple protective effects against endothelial dysfunction, vascular inflammation, and blood-retinal barrier (BRB) breakdown. However, the effect of melatonin on CSC, and its exact pathogenesis, is not well understood thus far. In this study, an experimental model was established by intravitreal injection of aldosterone in rats, which mimicked the features of CSC. Our results found that melatonin administration in advance significantly inhibited aldosterone-induced choroidal thickening and vasodilation by reducing the expression of calcium-activated potassium channel KCa2.3, and attenuated tortuosity of choroid vessels. Moreover, melatonin protected the BRB integrity and prevented the decrease in tight junction protein (ZO-1, occludin, and claudin-1) levels in the rat model induced by aldosterone. Additionally, the data also showed that intraperitoneal injection of melatonin in advance inhibited aldosterone-induced macrophage/microglia infiltration, and remarkably diminished the levels of inflammatory cytokines (interleukin-6 [IL-6], IL-1ß, and cyclooxygenase-2), chemokines (chemokine C-C motif ligand 3, and C-X-C motif ligand 1), and matrix metalloproteinases (MMP-2 and MMP-9). Luzindole, as the nonselective MT1 and MT2 antagonist, and 4-phenyl-2-propionamidotetraline, as the selective MT2 antagonist, neutralized the melatonin-induced inhibition of choroidal thickening and choroidal vasodilation, indicating that melatonin might exert the effects via binding to its receptors. Furthermore, the IL-17A/nuclear factor-κB signaling pathway was activated by intravitreal administration of aldosterone, while it was suppressed in melatonin-treated in advance rat eyes. This study indicates that melatonin could serve as a promising safe therapeutic strategy for CSC patients.

Anti-PANoptosis is involved in neuroprotective effects of melatonin in acute ocular hypertension model.

Acute ocular hypertension (AOH) is the most important characteristic of acute glaucoma, which can lead to retinal ganglion cell (RGC) death and permanent vision loss. So far, approved effective therapy is still lacking in acute glaucoma. PANoptosis (pyroptosis, apoptosis, and necroptosis), which consists of three key modes of programmed cell death-apoptosis, necroptosis, and pyroptosis-may contribute to AOH-induced RGC death. Previous studies have demonstrated that melatonin (N-acetyl-5-methoxytryptamine) exerts a neuroprotective effect in many retinal degenerative diseases. However, whether melatonin is anti-PANoptotic and neuroprotective in the progression of acute glaucoma remains unclear. Thus, this study aimed to explore the role of melatonin in AOH retinas and its underlying mechanisms. The results showed that melatonin treatment attenuated the loss of ganglion cell complex thickness, retinal nerve fiber layer thickness, and RGC after AOH injury, and improved the amplitudes of a-wave, b-wave, and oscillatory potentials in the electroretinogram. Additionally, the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells was decreased, and the upregulation of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 and p-Bad were inhibited after melatonin administration. Meanwhile, both the expression and activation of MLKL, RIP1, and RIP3, along with the number of PI-positive cells, were reduced in melatonin-treated mice, and p-RIP3 was in both RGC and microglia/macrophage after AOH injury. Furthermore, melatonin reduced the expression of NLRP3, ASC, cleaved caspase-1, gasdermin D (GSDMD), and cleaved GSDMD, and decreased the number of Iba1/interleukin-1ß-positive cells. In conclusion, melatonin ameliorated retinal structure, prevented retinal dysfunction after AOH, and exerted a neuroprotective effect via inhibition of PANoptosis in AOH retinas.

Comparison of pregnancy outcomes between GnRH antagonist protocol with freeze-all strategy and long-acting GnRH agonist protocol in women with adenomyosis undergoing IVF/ICSI: a propensity-score matching analysis.

BACKGROUND: Plenty of studies explored the most optimal treatment protocol for infertile women with adenomyosis in in-vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI), however, there is still no consensus on which treatment protocol is ideal for these women at present. So, we conducted this study comparing the pregnancy outcomes in infertile women with ultrasound-diagnosed adenomyosis who underwent GnRH antagonist protocol with freeze-all strategy or long-acting GnRH agonist protocol. METHODS: This was a retrospective cohort study and a propensity-score matching (PSM) analysis including 282 women diagnosed with adenomyosis undergoing their first IVF/ICSI cycle from January 2016 to July 2021 at the Assisted Reproduction Center, Northwest Women's and Children's Hospital, China. The patients were divided into two groups: the GnRH antagonist protocol with freeze-all strategy (n = 168) and the long-acting GnRH agonist protocol with fresh embryo transfer (n = 114) according their treatment protocols. The primary outcome was live birth rate. Cumulative live birth rate was also calculated. RESULTS: After adjusting for confounders, clinical pregnancy rate (49.40% vs 64.04%; odds ratio (OR) 1.33; 95% confidence interval (CI) 0.70 to 2.37; P = 0.358), live birth rate (36.90% vs 45.61%; OR 1.10; 95% CI 0.61 to 2.00, P = 0.753) and cumulative live birth rate (51.79% vs 64.04%; OR 1.01; 95% CI 0.49 to 1.74, P = 0.796) were not significantly different between the GnRH antagonist protocol with freeze-all strategy and long-acting GnRH agonist protocol. Similar results were conducted in PSM analysis with clinical pregnancy rate (46.48% vs 60.56%; OR 1.33; 95% CI 0.76 to 2.34; P = 0.321), live birth rate (32.39% vs 45.07%; OR 1.31; 95% CI 0.63 to 2.72, P = 0.463) and cumulative live birth rate (54.90% vs 60.60%; OR 1.01; 95% CI 0.59 to 1.74, P = 0.958). CONCLUSIONS: For infertile women with adenomyosis, these two treatment protocols resulted in similar pregnancy outcomes. Larger, prospective studies are needed in the future.

INFLUENCE OF HIGH MYOPIA ON CHORIOCAPILLARIS PERFUSION AND CHOROIDAL THICKNESS IN DIABETIC PATIENTS WITHOUT DIABETIC RETINOPATHY.

PURPOSE: To investigate the impact of high myopia on choriocapillaris perfusion and choroidal thickness (CT) in diabetic patients without diabetic retinopathy. METHODS: Healthy subjects and patients with diabetes mellitus were recruited from communities in Guangzhou. They were divided into four groups according to the presence of diabetes and high myopia: healthy control (n = 77), diabetes (n = 77), high myopia (n = 77), and diabetes with high myopia (n = 77). Swept-source optical coherence tomography angiography (SS-OCTA) measured choriocapillaris perfusion and CT. Choriocapillaris perfusion was quantified using the choriocapillaris perfusion index (CPI). RESULTS: A total of 308 subjects (308 eyes) were included in the study. The average CPI was 91.11 ± 0.84, 90.16 ± 1.46, 89.80 ± 1.42, and 89.36 ± 1.19% in the control, diabetes, high myopia, and diabetes with high myopia groups, respectively (P < 0.001); the average CT was 227.55 ± 43.13, 205.70 ± 59.66, 158.38 ± 45.24, and 144.22 ± 45.12 µm, respectively (P < 0.001). After adjusting for age and sex, the average CPI decreased 0.95 ± 0.20% (P < 0.001) in the diabetes group, 1.33 ± 0.20% (P < 0.001) in the high myopia group, and 1.76 ± 0.20% (P < 0.001) in the diabetes with high myopia group relative to the control group; the average CT decreased 23.53 ± 8.12 (P = 0.004), 70.73 ± 9.41 (P < 0.001), and 85.90 ± 8.12 µm (P < 0.001), respectively. Further adjustment for other risk factors yielded a similar result. CONCLUSION: Diabetes and high myopia significantly affect CPI and CT, and the presence of both conditions is more damaging to CPI and CT than diabetes or high myopia alone.

Does a beautiful environment make food better - The effect of environmental aesthetics on food perception and eating intention.

Generally, people prefer to dine in beautiful environments. Previous studies have reported that environmental factors affect an individual's perception of food; however, little is known about the effect of environmental aesthetics on food perception. In Experiment 1, we used photographs of restaurant (1a) or non-restaurant (1b) environments with high or low aesthetic value, paired with images of foods, and participants were asked to rate the visual, olfactory, and gustatory aesthetic value of the food. Results showed significantly higher ratings for food perception in all three sensory modalities in the high aesthetic value environment, together with positive emotion and the desire to eat, compared with the low aesthetic environment. Experiment 2 extended the study to two real-world environments (one high and one low aesthetic value) and actual food consumption. The results also found higher aesthetic ratings in the olfactory and gustatory systems and greater desire to eat again in an environment with high aesthetic value than in an environment with low aesthetic value. This research also explored the mediating role of emotion in the relationship between environmental aesthetics and food perception and found a significant mediating relationship. In conclusion, environmental aesthetics play an important role in food perception, and these findings provide insights into increasing positive food perception in daily life.

The ideal harvest time for seed production in maize (Zea mays L.) varieties of different maturity groups.

BACKGROUND: The correct time for harvesting is a key factor contributing to the production of high-quality maize seeds. We conducted field experiments to harvest seeds at 11 developmental stages for 3 years, to investigate seed vigor traits in three early maturity maize varieties and two late maturity varieties in one location. RESULTS: Significant correlations (r = 0.72 ~ 0.89) were found among six seed-related traits: standard germination (SG), accelerated aging germination (AAG), cold test germination (CTG), hundred-seed weight (HSW), seed moisture content (SMC), and ≥ 10 °C accumulated temperature from pollination to harvest (AT10). Analysis of variance showed that harvest stage, year, and variety had significant effects on all traits, and harvest stage displayed the greatest effect. The responses of SG, AAG, CTG, HSW and SMC to harvest stage fitted quadratic models, and AT10 fitted a linear model. From the quadratic models, an ideal harvest time (IHT, the final date to reach maximum SG, AAG, and CTG) could be calculated for each variety. The three early maturity varieties reached their IHT at 54.94-58.44 days after pollination (DAP); the two later maturity varieties reached IHT several days later (at 59.87-59.90 DAP). The early maturity varieties consistently required less AT10 to reach the IHT than the later maturity varieties. However, all of the varieties reached the IHT at similar SMC levels of about 35%. CONCLUSION: The later maturity varieties reached the IHT at later DAPs when they acquired more AT10 than the early maturity varieties but both reached it at similar SMC levels. © 2022 Society of Chemical Industry.

Ugly food, not eat: the eating intention of emotional eater for different esthetic food.

BACKGROUND: Emotional eaters eat to relieve their emotions. However, food also contains esthetic information. People generally perceive ugly food as unhealthy and unpalatable. Does the esthetic information of food influence an emotional eater's desire for food in a negative emotional state? In particular, do they have the same lower eating intentions for low esthetic food as non-emotional eaters? OBJECTIVE/DESIGN/MEASURES: Based on these questions, the present study examined whether the esthetic value of food influences emotional eaters' desires for food. The experiment used a 2 (eating type: emotional eating vs. non-emotional eating) × 2 (food style: high esthetic vs. low esthetic) mixed experimental design. We measured the emotional and non-emotional eaters' eating intentions for different esthetic foods when experiencing negative emotions. RESULTS: The results showed that emotional eaters have higher intention to eat high esthetic foods. However, they did not have a high eating intention for all foods, and their eating intention did not differ from that of non-emotional eaters when faced with low esthetic food. CONCLUSION: In conclusion, food esthetic value can affect individual eating intentions. Even for emotional eaters who are in a negative mood, they also did not have a higher eating intention for low esthetic food compared with no-emotional eater. LEVEL OF EVIDENCE: Level II: controlled trial without randomization.

The phase changes of M1/M2 phenotype of microglia/macrophage following oxygen-induced retinopathy in mice.

OBJECTIVE: Microglia/macrophage activation is previously reported to be involved in various ocular diseases. However, the separate role of M1/M2 phenotype microglia/macrophage in the pathological process of oxygen-induced retinopathy (OIR) remains unknown. In this research, we explored the role and regulatory mechanism of M1/M2 microglia/macrophage in OIR in C57BL/6J mice. Furthermore, we demonstrated the time phase of M1/M2 shifting of microglia/macrophage during the natural process of OIR, which is very essential for further investigations. MATERIALS AND METHODS: C57BL/6j pups were exposed to hyperoxia environment from postnatal 7(P7) to P12 then returned to normoxia. The mice were then euthanized, and the eyes were harvested at a series of time points for further investigation. The M1/M2 phenotype microglia/macrophage activity was presented by immunofluorescent staining and real-time quantitative polymerase chain reaction (qPCR). The NF-κb-STAT3 signaling and IL-4-STAT6-PPAR-γ signaling pathway activity was examined by western blot analysis. RESULTS: The microglia/macrophage were activated when the OIR model was set up after P12. The M1 microglia/macrophage activation was found in neovascularization (NV) tufts in both central and peripheral retina, which started from P12 when the mice were returned to normoxia environment and peaked at P17. During this period of time, the NF-κb-STAT3 signaling pathway was activated, resulting in the upregulated M1 phenotype microglia/macrophage polarization, along with the enhanced inflammatory cytokine expression including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß. Consequently, the NV tufts were observed from P12 and the volume continued to increase until P17. However, the M2 phenotype microglia/macrophage activity took over during the late phase of OIR started from P17. The IL-4-STAT6-PPAR-γ signaling activity was upregulated from P17 and peaked at P20, inducing M2 phenotype microglia polarization, which consequently led to the inhibition of inflammatory cytokines and spontaneous regression of NV tufts. CONCLUSIONS: Microglia/macrophage participate actively in the natural process of OIR in mice, and two phenotypes exert different functions. Treatment modulating microglia/macrophage polarize toward M2 phenotype might be a novel and promising method for ocular neovascular diseases such as retinopathy of prematurity (ROP), wet age-related macular degeneration (wAMD), and diabetic retinopathy (DR).

Melatonin protects inner retinal neurons of newborn mice after hypoxia-ischemia.

Retinopathy of prematurity is a vision-threatening disease associated with retinal hypoxia-ischemia, leading to the death of retinal neurons and chronic neuronal degeneration. During this study, we used the oxygen-induced retinopathy mice model to mimic retinal hypoxia-ischemia phenotypes to investigate further the neuroprotective effect of melatonin on neonatal retinal neurons. Melatonin helped maintain relatively normal inner retinal architecture and thickness and preserve inner retinal neuron populations in avascular areas by rescuing retinal ganglion and bipolar cells, and horizontal and amacrine neurons, from apoptosis. Meanwhile, melatonin recovered visual dysfunction, as reflected by the improved amplitudes and implicit times of a-wave, b-wave, and oscillatory potentials. Additionally, elevated cleaved caspase-3 and Bax protein levels and reduced Bcl-2 protein levels in response to hypoxia-ischemia were diminished after melatonin treatment. Moreover, melatonin increased BDNF and downstream phospho-TrkB/Akt/ERK/CREB levels. ANA-12, a TrkB receptor antagonist, antagonized these melatonin actions and reduced melatonin-induced neuroprotection. Furthermore, melatonin rescued the reduction in melatonin receptor expression. This study suggests that melatonin exerted anti-apoptotic and neuroprotective effects in inner retinal neurons after hypoxia-ischemia, at least partly due to modulation of the BDNF-TrkB pathway.

Antigen-Specific TCR Signatures of Cytomegalovirus Infection.

CMV is a prevalent human pathogen. The virus cannot be eliminated from the body, but is kept in check by CMV-specific T cells. Patients with an insufficient T cell response, such as transplant recipients, are at high risk of developing CMV disease. However, the CMV-specific T cell repertoire is complex, and it is not yet clear which T cells protect best against virus reactivation and disease. In this study, we present a highly resolved characterization of CMV-specific human CD8+ T cells based on enrichment by specific peptide stimulation and mRNA sequencing of their TCR ß-chains (TCRß). Our analysis included recently identified T cell epitopes restricted through HLA-C, whose presentation is resistant to viral immunomodulation, and well-studied HLA-B-restricted epitopes. In eight healthy virus carriers, we identified a total of 1052 CMV-specific TCRß sequences. HLA-C-restricted, CMV-specific TCRß clonotypes dominated the ex vivo T cell response and contributed the highest-frequency clonotype of the entire repertoire in two of eight donors. We analyzed sharing and similarity of CMV-specific TCRß sequences and identified 63 public or related sequences belonging to 17 public TCRß families. In our cohort, and in an independent cohort of 352 donors, the cumulative frequency of these public TCRß family members was a highly discriminatory indicator of carrying both CMV infection and the relevant HLA type. Based on these findings, we propose CMV-specific TCRß signatures as a biomarker for an antiviral T cell response to identify patients in need of treatment and to guide future development of immunotherapy.