The transcription factor MYB110 regulates plant height, lodging resistance, and grain yield in rice.

The high-yielding Green Revolution varieties of cereal crops are characterized by a semidwarf architecture and lodging resistance. Plant height is tightly regulated by the availability of phosphate (Pi), yet the underlying mechanism remains obscure. Here, we report that rice (Oryza sativa) R2R3-type Myeloblastosis (MYB) transcription factor MYB110 is a Pi-dependent negative regulator of plant height. MYB110 is a direct target of PHOSPHATE STARVATION RESPONSE 2 (OsPHR2) and regulates OsPHR2-mediated inhibition of rice height. Inactivation of MYB110 increased culm diameter and bending resistance, leading to enhanced lodging resistance despite increased plant height. Strikingly, the grain yield of myb110 mutants was elevated under both high- and low-Pi regimes. Two divergent haplotypes based on single nucleotide polymorphisms in the putative promoter of MYB110 corresponded with its transcript levels and plant height in response to Pi availability. Thus, fine-tuning MYB110 expression may be a potent strategy for further increasing the yield of Green Revolution cereal crop varieties.

Interpregnancy interval and early infant neurodevelopment: the role of maternal-fetal glucose metabolism.

BACKGROUND: Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal-fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment. METHODS: This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24-28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted. RESULTS: In our cohort, 14.0% had an IPI < 12 months. IPI < 12 months increased the failure of the communication domain, fine motor domain, and personal social domain of the ASQ (relative risks (RRs) with 95% confidence interval (CI): 1.73 [1.11,2.70]; 1.73 [1.10,2.72]; 1.51 [1.00,2.29]). Maternal homeostasis model assessment of insulin resistance (HOMA-IR) and cord blood C-peptide was significantly associated with failure in the communication domain [RRs with 95% CI: 1.15 (1.02, 1.31); 2.15 (1.26, 3.67)]. The proportion of the association between IPI and failure of the communication domain risk mediated by maternal HOMA-IR and cord blood C-peptide was 14.4%. CONCLUSIONS: IPI < 12 months was associated with failing the communication domain in infants. Maternal-fetal glucose metabolism abnormality may partially explain the risk of neurodevelopmental delay caused by short IPI.

Identification of microRNAs and their target genes associated with chasmogamous and cleistogamous flower development in Viola prionantha.

MAIN CONCLUSION: Differentially expressed microRNAs were found associated with the development of chasmogamous and cleistogamous flowers in Viola prionantha, revealing potential roles of microRNAs in the developmental evolution of dimorphic flowers. In Viola prionantha, chasmogamous (CH) flowers are induced by short daylight, while cleistogamous (CL) flowers are triggered by long daylight. How environmental factors and microRNAs (miRNAs) affect dimorphic flower formation remains unknown. In this study, small RNA sequencing was performed on CH and CL floral buds at different developmental stages in V. prionantha, differentially expressed miRNAs (DEmiRNAs) were identified, and their target genes were predicted. In CL flowers, Viola prionantha miR393 (vpr-miR393a/b) and vpr-miRN3366 were highly expressed, while in CH flowers, vpr-miRN2005, vpr-miR172e-2, vpr-miR166m-3, vpr-miR396f-2, and vpr-miR482d-2 were highly expressed. In the auxin-activated signaling pathway, vpr-miR393a/b and vpr-miRN2005 could target Vpr-TIR1/AFB and Vpr-ARF2, respectively, and other DEmiRNAs could target genes involved in the regulation of transcription, e.g., Vpr-AP2-7. Moreover, Vpr-UFO and Vpr-YAB5, the main regulators in petal and stamen development, were co-expressed with Vpr-TIR1/AFB and Vpr-ARF2 and showed lower expression in CL flowers than in CH flowers. Some V. prionantha genes relating to the stress/defense responses were co-expressed with Vpr-TIR1/AFB, Vpr-ARF2, and Vpr-AP2-7 and highly expressed in CL flowers. Therefore, in V. prionantha, CH-CL flower development may be regulated by the identified DEmiRNAs and their target genes, thus providing the first insight into the formation of dimorphic flowers in Viola.

Heterogeneous Porous Synergistic Photocatalysts for Organic Transformations.

Recent interest has surged in using heterogeneous carriers to boost synergistic photocatalysis for organic transformations. Heterogeneous catalysts not only facilitate synergistic enhancement of distinct catalytic centers compared to their homogeneous counterparts, but also allow for the easy recovery and reuse of catalysts. This mini-review summarizes recent advancements in developing heterogeneous carriers, including metal-organic frameworks, covalent-organic frameworks, porous organic polymers, and others, for synergistic catalytic reactions. The advantages of porous materials in heterogeneous catalysis originate from their ability to provide a high surface area, facilitate enhanced mass transport, offer a tunable chemical structure, ensure the stability of active species, and enable easy recovery and reuse of catalysts. Both photosensitizers and catalysts can be intricately incorporated into suitable porous carriers to create heterogeneous dual photocatalysts for organic transformations. Notably, experimental evidence from reported cases has shown that the catalytic efficacy of heterogeneous catalysts often surpasses that of their homogeneous analogues. This enhanced performance is attributed to the proximity and confinement effects provided by the porous nature of the carriers. It is expected that porous carriers will provide a versatile platform for integrating diverse catalysts, thus exhibiting superior performance across a range of organic transformations and appealing prospect for industrial applications.

A new simplified sequence-dependent loop-mediated isothermal amplification (LAMP) detection method.

Fluorescence dye-based loop-mediated isothermal amplification (LAMP) is a sensitive nucleic acid detection method, but is limited to single-plex detection and may yield non-specific signals. In this study, we propose a bifunctional probe-based real-time LAMP amplification method for single-plexed or multiplexed detection. The bifunctional probe is derived by modifying the 5' end of the fluorophore and an internal quencher on one of the LAMP primers; therefore, it can simultaneously be involved in the LAMP process and signal amplification. The fluorescence intensity undergoes a cumulative exponential increase during the incorporation of the bifunctional probe into double-stranded DNA amplicons. The bifunctional probe-based LAMP method is simplified and cost-effective, as the primer design and experimental operations align entirely with the ordinary LAMP. Different from other current probe-based methods, this method does not require additional enzymes, sequences, or special probe structures. Also, it is 10 min faster than several other probe-based LAMP methods. The bifunctional probe-based LAMP method allows the simultaneous detection of the target Vibrio parahaemolyticus DNA and the internal amplification control in a one-pot reaction, demonstrating its potential for multiplexed detection.

Non-peptidic inhibitors targeting SARS-CoV-2 main protease: A review.

The COVID-19 pandemic continues to pose a threat to global health, and sounds the alarm for research & development of effective anti-coronavirus drugs, which are crucial for the patients and urgently needed for the current epidemic and future crisis. The main protease (Mpro) stands as an essential enzyme in the maturation process of SARS-CoV-2, playing an irreplaceable role in regulating viral RNA replication and transcription. It has emerged as an ideal target for developing antiviral agents against SARS-CoV-2 due to its high conservation and the absence of homologous proteases in the human body. Among the SARS-CoV-2 Mpro inhibitors, non-peptidic compounds hold promising prospects owing to their excellent antiviral activity and improved metabolic stability. In this review, we offer an overview of research progress concerning non-peptidic SARS-CoV-2 Mpro inhibitors since 2020. The efforts delved into molecular structures, structure-activity relationships (SARs), biological activity, and binding modes of these inhibitors with Mpro. This review aims to provide valuable clues and insights for the development of anti-SARS-CoV-2 agents as well as broad-spectrum coronavirus Mpro inhibitors.

Associations between particulate matter exposure during pregnancy and executive function of toddlers in a prospective cohort study.

BACKGROUND: Exposure to particulate matter (PM) has been found to be associated with impaired cognitive function. However, limited evidence is available on the relationship between PM exposure in the prenatal period and toddler executive function (EF), and the potential influence of breastfeeding. METHODS: The study included 1106 mother-toddler pairs recruited between 2015 and 2019. We assessed mothers' PM1, PM2.5, and PM10 prenatal exposure with a satellite-based dataset at a 1 × 1 km spatial resolution and assigned to participants based on residential addresses. Toddler EF was measured using the Behavior Rating Inventory of Executive Function for Preschoolers (BRIEF-P) questionnaire, higher BRIEF-P scores indicated poorer EF in toddlers. We determined the associations of PM exposure during pregnancy with BRIEF-P scores using multiple linear regression models. RESULTS: In the first trimester, a 10 µg/m3 increase of PM was associated with 1.49 (95% confidence interval [CI]: 0.14-2.83; PM1), 0.68 (95% CI: 0.10-1.26; PM2.5), and 0.63 (95% CI: 0.07-1.20; PM10) elevated toddler global executive composite index scores, respectively. In the stratified analysis, a 10 µg/m3 increase in first trimester PM1 exposure was related to 0.54 (95% CI: 0.19-0.89) higher inhibition scores in toddlers who received complementary breastfeeding for less than six months and -0.15 (95% CI: 0.81-0.51) higher inhibition scores in toddlers who received complementary breastfeeding for six months or more (P for interaction: 0.046). Additionally, a 10 µg/m3 increment in first trimester PM1 exposure was related to 0.36 (95% CI: 0.13-0.59) higher emotional control scores in toddlers who received breastfeeding for less than 12 months and -0.54 (95% CI: 1.25-0.18) higher inhibition scores in toddlers who received breastfeeding for no less than 12 months (P for interaction: 0.043). CONCLUSIONS: PM exposure during the first trimester, especially PM1, has been linked to lower toddler EF performance in toddlers; feeding with breast milk may be a potential protective measure.

Association between exposure to outdoor artificial light at night during pregnancy and glucose homeostasis: A prospective cohort study.

BACKGROUND: Outdoor artificial light at night (ALAN) has been linked to an elevated risk of diabetes, but the available literature on the relationships between ALAN and glucose homeostasis in pregnancy is limited. METHODS: A prospective cohort study of 6730 pregnant women was conducted in Hefei, China. Outdoor ALAN exposure was estimated using satellite data with individual addresses at a spatial resolution of approximately 1 km, and the average ALAN intensity was calculated. Gestational diabetes mellitus (GDM) was diagnosed based on a standard 75-g oral glucose tolerance test. Multivariable linear regression and logistic regression were used to estimate the relationships between ALAN and glucose homeostasis. RESULTS: Outdoor ALAN was associated with elevated glucose homeostasis markers in the first trimester, but not GDM risk. An increase in the interquartile range of outdoor ALAN values was related to a 0.02 (95% confidence interval [CI]: 0.00, 0.03) mmol/L higher fasting plasma glucose, a 0.42 (95% CI: 0.30, 0.54) µU/mL increase in insulin and a 0.09 (95% CI: 0.07, 0.12) increase in homeostatic model assessment of insulin resistance (HOMA-IR) during the first trimester. Subgroup analyses showed that the associations between outdoor ALAN exposure and fasting plasma glucose, insulin, and HOMA-IR were more pronounced among pregnant women who conceived in summer and autumn. CONCLUSIONS: The results provided evidence that brighter outdoor ALAN in the first trimester was related to elevated glucose intolerance in pregnancy, especially in pregnant women conceived in summer and autumn, and effective strategies are needed to prevent and manage light pollution.

Progression of enlarged perivascular spaces contributes to occurrence of silent lacunar infarction in the elderly.

INTRODUCTION: This study aims to assess the effect of enlarged perivascular spaces (EPVS) in patients using the methods of scale score and 3D volume quantification and to determine whether EPVS progression is related to the occurrence of silent lacunar infarction (SLI). METHOD: Three hundred sixty-seven elderly patients with EPVS were screened by MRI on the day of admission and 2 years later; 295 patients were included in the final study, among which 136 patients had EPVS with SLI (EL); and 159 patients had EPVS without SLI (EOL). Both scale score and 3D volume quantification method were used to evaluate EPVS. The 295 patients were divided into three groups based on EPVS progression state: Group 1 (no progression), Group 2 (0-50% EPVS progression), and Group 3 (≥ 50% EPVS progression). Multiple logistic regression analysis was used to analyze the risk of occurrence of SLI. RESULTS: The EPVS scores and ΔEPVS scores were not significantly different between the EL and EOL groups (p > 0.05). EPVS volumes and their progression were significantly higher in EL compared with EOL (p < 0.001). The incidence of SLI was increased in Groups 2 and 3 compared with those in Group 1, and the trend test showed statistically significant (p = 0.032). Multiple logistic regression analysis showed that the risk of occurrence of SLI was significantly increased in Group 2 (OR 2.24; p = 0.024) and Group 3 (OR 3.31; p = 0.037) versus that in Group 1. CONCLUSION: 3D volume quantification allows for a more sensitive assessment of EPVS changes, and the progression of EPVS volume may contribute to the occurrence of SLI.

Realization path and connotation of the Healthy China strategy: macroscopic perspective of dietary structure and the entry of individual health consciousness.

BACKGROUND: Dietary rationality and health concept have certain influence on individual health level. This study aims to explore the characteristics and existing problems of Chinese residents' health behaviors from both macro and micro perspectives, and explore the feasibility and realization path of Healthy China strategy. METHODS: We utilized regression models to evaluate the correlation between diet and the risk of disease causes of death. By use of the linear regression analysis model, we distinguished the impact of each dimension on health literacy index at the individual level. Then, we explored the influential factors of the diet health index using the binary logit regression model. RESULTS: Increased consumption of animal-derived foods in China has contributed to the burden of non-communicable diseases. The individuals' health awareness is still weak, and the health literacy index is greatly affected by the diet, while the individual gender and age are positively correlated with the diet health index, and the individual body mass index (BMI) level is negatively correlated with the diet health index. CONCLUSIONS: This study provided a comprehensive understanding of existing problems of Chinese residents' health behaviors. We have proposed a path model for the implementation of the Healthy China strategy from the perspectives of "diet health, physical health, conceptual health and environmental health," which is also a great contribution to the world.

Evaluation of the Optimal Duration of Thumb Cupping Therapy for Frozen Shoulder by Thermal Metabolic Imaging.

Objective: To evaluate the optimal duration of thumb cupping therapy for frozen shoulder (FS) by thermal metabolic imaging (TMI) and to provide clinical evidence. Methods: From April 2022 to August 2023, 120 patients with FS who received thumb cupping therapy at our hospital were randomized into groups A, B, and C for 5, 10, and 15 minutes of cupping, respectively. The clinical efficacy, Visual Analogue Scale (VAS) score, and shoulder range of motion (ROM) of the three groups were compared, and the skin blood flow and the incidence of adverse reactions during treatment were analyzed. Finally, the temperature difference improvement efficiency (i.e., higher TMI after treatment than before treatment) was compared among the three groups. Results: Groups B and C showed higher overall clinical efficacy than group A (P < .05). After treatment, lower VAS scores were determined in groups B and C compared with group A, whereas the ROM values of groups A and C were smaller than those of group B Group C had the greatest skin blood flow and the highest incidence of adverse reactions (P < .05), while group B had the highest temperature difference improvement efficiency (P < .05). Conclusions: Through TMI, it is confirmed that thumb cupping therapy with a duration of 10 min contributes to the highest efficacy and safety for patients with FS.

Left ventricle-right atrial communication: A specific type of ventricular septal defect.

Left ventricular-right atrial communication (LV-RAC) refers to the shunt from the left ventricle to the right atrium caused by an abnormal channel between the left ventricle and the right atrium, and is a specific type of ventricular septal defect that is rare. We diagnosed one case using echocardiography.

Ultrasound manifestations of primary intestinal non-Hodgkin lymphoma with liver metastasis in a child.

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

Solid-Phase Microextraction/Gas Chromatography-Time-of-Flight Mass Spectrometry Approach Combined with Network Pharmacology Analysis to Evaluate the Quality of Agarwood from Different Regions against Anxiety Disorder.

Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography-time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound-target-disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.

Broadening the Voltage Window of 3D-Printed MXene Micro-Supercapacitors with a Hybridized Electrolyte.

The burgeoning demand for miniaturized energy storage devices compatible with the miniaturization trend of electronic technologies necessitates advancements in micro-supercapacitors (MSCs) that promise safety, cost efficiency, and high-speed charging capabilities. However, conventional aqueous MSCs face a significant limitation due to their inherently narrow electrochemical potential window, which restricts their operational voltage and energy density compared to their organic and ionic liquid counterparts. In this study, we introduce an innovative aqueous NaCl/H2O/EG hybrid gel electrolyte (comprising common salt (NaCl), H2O, ethylene glycol (EG), and SiO2) for Ti3C2Tx MXene MSCs that substantially widens the voltage window to 1.6 V, a notable improvement over traditional aqueous system. By integrating the hybrid electrolyte with 3D-printed MXene electrodes, we realized MSCs with remarkable areal capacitance (1.51 F cm-2) and energy density (675 µWh cm-2), significantly surpassing existing benchmarks for aqueous MSCs. The strategic formulation of the hybrid electrolyte-a low-concentration NaCl solution with EG-ensures both economic and environmental viability while enabling enhanced electrochemical performance. Furthermore, the MSCs fabricated via 3D printing technology exhibit exceptional flexibility and are suitable for modular device integration, offering a promising avenue for the development of high-performance, sustainable energy storage devices. This advancement not only provides a tangible solution to the challenge of limited voltage windows in aqueous MXene MSCs but also sets a new precedent for the design of next-generation MSCs that align with the needs of an increasingly microdevice-centric world.

IGF2BP2 enhances LincRNA01116 stability via m6 A: A potential biomarker and therapeutic target for patients with pre-eclampsia.

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6 A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.

Xihuang pill facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.

Glioma is the most common malignancy in the central nervous system. This study aims to disclose the impacts of Xihuang pill (XHP), a traditional Chinese formula, on glioma cell pyroptosis and relevant molecular mechanism. U251 and SHG-44 cells were treated with XHP alone or together with oe-POU4F1 and sh-STAT3. CCK8 assay detected the viability, flow cytometry evaluated pyroptosis, and microscopy observed cell morphology. LDH release was determined by the LDH kit and the levels of IL-1ß and IL-18 were detected by ELISA. Immunofluorescence showed NLRP3 expression in glioma cells and western blotting measured the levels of POU4F1, STAT3, NLRP3, ASC, cleaved caspase-1, and IL-1ß. The binding of POU4F1 to STAT3 was verified. Primary glioma model was established to observe tumor change by in vivo imaging, determine the levels of Ki67 and NLRP3 by immunochemistry, and detect relevant protein levels by western blotting. XHP treatment alone downregulated POU4F1 and STAT3 levels, aroused pyroptotic appearance in glioma cells such as ballooning swelling, reduced cell viability and number of pyroptotic cells, increased LDH release and IL-1ß and IL-18 levels, formed NLRP3 sports in cells, and elevated the levels of pyroptosis-related proteins. However, POU4F1 overexpression or STAT3 silencing suppressed XHP-promoted pyroptosis. Mechanistically, POU4F1 acted as a transcription factor of STAT3 and regulated its transcription. In primary glioma models, XHP enhanced glioma cell pyroptosis and blocked glioma growth. XHP facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.

Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. METHODS: Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. RESULTS: Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. CONCLUSIONS: These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis.

Survival and late mortality among patients who survived disease-free for 2 years after stem cell transplantation.

Most events that limit life expectancy after allogeneic haematopoietic stem cell transplantation (allo-HSCT) occur within the first 2 years; however, treatment outcomes in long-term survivors who survive for at least 2 years post-HSCT without relapse are yet to be elucidated. To explore the life expectancy trends and late complications and to assess the main mortality-related factors, we investigated the characteristics of patients who received allo-HSCT for haematological malignancies from 2007 to 2019 in our centre and survived in remission for 2 years. A cohort of 831 patients was enrolled; of these, 508 received grafts from haploidentical-related donors (61.1%). The estimated overall survival rate at 10 years was 91.9% (95% confidence interval [CI], 89.8-93.5), which was affected by prior grade III-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 2.98; 95% CI, 1.47-6.03; p = 0.002) and severe chronic GVHD (HR, 3.60; 95% CI, 1.93-6.71; p < 0.001). The probability of late relapse and non-relapse mortality at 10 years was 8.7% (95% CI, 6.9-10.8) and 3.6% (95% CI, 2.5-5.1) respectively. The top cause of late mortality was relapsed (49.0%). Projected long-term survival in 2-year disease-free survivors following allo-HSCT was excellent. Strategies should be implemented to minimise the late death-specific hazards in recipients.

GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet are involved in itch processing in mice.

Itch and pain are two closely related sensations that receiving similar encodings at multiple levels. Accumulated evidences suggest that activation of the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL)-to-lateral and ventrolateral periaqueductal gray (l/vlPAG) projections mediates the antinociceptive effects of bright light therapy. Clinical study showed that bright light therapy may ameliorate cholestasis-induced pruritus. However, the underlying mechanism and whether this circuit participates in itch modulation remains unclear. In this study, chloroquine and histamine were utilized to induce acute itch models in mice. Neuronal activities in vLGN/IGL nucleus were evaluated with c-fos immunostaining as well as fiber photometry. Optogenetic manipulations were performed to activate or inhibit GABAergic neurons in the vLGN/IGL nucleus. Our results showed that the expressions of c-fos in vLGN/IGL were significantly increased upon both chloroquine- and histamine-induced acute itch stimuli. GABAergic neurons in vLGN/IGL were activated during histamine and chloroquine-induced scratching. Optogenetic activation of the vLGN/IGL GABAergic neurons exerts antipruritic effect, while inhibiting these neurons exerts pruritic effect. Our results provide evidence that GABAergic neurons in vLGN/IGL nucleus might play a crucial role in modulating itch, which may provide clue for application of bright light as an antipruritic treatment in clinic.