Giant magnetocaloric effect in spin supersolid candidate Na2BaCo(PO4)2.

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.

The Effects of Age and Reading Experience on the Lifespan Neurodevelopment for Reading Comprehension.

Reading comprehension is a vital cognitive skill that individuals use throughout their lives. The neurodevelopment of reading comprehension across the lifespan, however, remains underresearched. Furthermore, factors such as maturation and experience significantly influence functional brain development. Given the complexity of reading comprehension, which incorporates lower-level word reading process and higher-level semantic integration process, our study aims to investigate how age and reading experience influence the neurobiology underpinning these two processes across the lifespan. fMRI data of 158 participants aged from 7 to 77 years were collected during a passive word viewing task and a sentence comprehension task to engage the lower- and higher-level processes, respectively. We found that the neurodevelopment of the lower-level process was primarily influenced by age, showing increased activation and connectivity with age in parieto-occipital and middle/inferior frontal lobes related to morphological-semantic mapping while decreased activation in the temporoparietal regions linked to phonological processing. However, the brain function of the higher-level process was primarily influenced by reading experience, exhibiting a greater reliance on the frontotemporal semantic network with enhanced sentence-level reading performance. Furthermore, reading experience did not significantly affect the brain function of children, but had a positive effect on young adults in the lower-level process and on middle-aged and older adults in the higher-level process. These findings indicate that the brain function for lower- and higher-level processes of reading comprehension is differently affected by maturation and reading experience, and the experience effect is contingent on age regarding the two processes.

PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy.

OBJECTIVE: This study aims to develop physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) predictive models for nifedipine in pregnant women, enhancing precision medicine and reducing adverse reactions for both mothers and infants. METHODS: A PBPK/PD model was constructed using PK-Sim, MoBi, and MATLAB software, integrating literature and pregnancy-specific physiological information. The process involved: (1) establishing and validating a PBPK model for serum clearance after intravenous administration in non-pregnant individuals, (2) establishing and validating a PBPK model for serum clearance after oral administration in non-pregnant individuals, (3) constructing and validating a PBPK model for enzyme clearance after oral administration in non-pregnant individuals, and (4) adjusting the PBPK model structure and enzyme parameters according to pregnant women and validating it in oral administration. (5) PK/PD model was explored through MATLAB, and the PBPK and PK/PD models were integrated to form the PBPK/PD model. RESULTS: The Nifedipine PBPK model's predictive accuracy was confirmed by non-pregnant and pregnant validation studies. The developed PBPK/PD model accurately predicted maximum antihypertensive effects for clinical doses of 5, 10, and 20 mg. The model suggested peak effect at 0.86 h post-administration, achieving blood pressure reductions of 5.4 mmHg, 14.3 mmHg, and 21.3 mmHg, respectively. This model provides guidance for tailored dosing in pregnancy-induced hypertension based on targeted blood pressure reduction. CONCLUSION: Based on available literature data, the PBPK/PD model of Nifedipine in pregnancy demonstrated good predictive performance. It will help optimize individualized dosing of Nifedipine, improve treatment outcomes, and minimize the risk of adverse reactions in mothers and infants.

Enhanced immunomodulation and periodontal regeneration efficacy of subgingivally delivered progranulin-loaded hydrogel as an adjunct to non-surgical treatment for Class II furcation involvement in dogs.

AIM: To evaluate the effect of subgingival delivery of progranulin (PGRN)/gelatin methacryloyl (GelMA) complex as an adjunct to scaling and root planing (SRP) on an experimental periodontitis dog model with Class II furcation involvement (FI). MATERIALS AND METHODS: A Class II FI model was established, and the defects were divided into four treatment groups: (a) no treatment (control); (b) SRP; (c) SRP + GelMA; (d) SRP + PGRN/GelMA. Eight weeks after treatment, periodontal parameters were recorded, gingival crevicular fluid and gingival tissue were collected for ELISA and RT-qPCR, respectively, and mandibular tissue blocks were collected for micro computed tomography (micro-CT) scanning and hematoxylin and eosin (H&E) staining. RESULTS: The SRP + PGRN/GelMA group showed significant improvement in all periodontal parameters compared with those in the other groups. The expression of markers related to M1 macrophage and Th17 cell significantly decreased, and the expression of markers related to M2 macrophage and Treg cell significantly increased in the SRP + PGRN/GelMA group compared with those in the other groups. The volume, quality and area of new bone and the length of new cementum in the root furcation defects of the PGRN/GelMA group were significantly increased compared to those in the other groups. CONCLUSIONS: Subgingival delivery of the PGRN/GelMA complex could be a promising non-surgical adjunctive therapy for anti-inflammation, immunomodulation and periodontal regeneration.

Retinal and choroidal structure and vascularity in Chinese emmetropic and myopic children.

PURPOSE: This study evaluated the structural features of the retinal and choroidal regions and their correlations with ocular biometric and vascular parameters in Chinese children using optical coherence tomography angiography (OCTA). METHODS: A total of 159 children, 6-13 years of age, were included in this prospective study. The sample consisted of 55 emmetropes (spherical equivalent ≤ +0.75 and > -0.50 D), 53 low-moderate myopes (≤ -0.50 to > -6.00 D) and 51 high myopes without pathological changes (≤ -6.00 D). Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Swept-source optical coherence tomography/OCTA was used to assess the macular structures and vascular characteristics in a 6 × 6 mm region centred on the macula. RESULTS: In a comprehensive analysis adjusting for age, sex, AL, macular blood perfusion, intraocular pressure and anterior segment parameters, retinal thickness (RT) showed a significant positive association with deep retinal vascular density and superficial retinal vascular density in the foveal area, but not with AL. Moreover, RT exhibited a significant negative association with AL in the parafoveal and perifoveal regions. Further, a significant positive correlation was observed between choroidal thickness and both choroidal vascular volume and choriocapillaris perfusion area, along with a negative correlation with AL across the entire macular region. CONCLUSIONS: This study showed that the thickness of retina and choroid in Chinese children was not only associated with AL but also showed dynamic properties such as the blood perfusion of the retina and choroid, particularly in the foveal area.

Highly efficient biosynthesis of salidroside by a UDP-glucosyltransferase-catalyzed cascade reaction.

OBJECTIVE: Salidroside is an important plant-derived aromatic compound with diverse biological properties. The main objective of this study was to synthesize salidroside from tyrosol using UDP-glucosyltransferase (UGT) with in situ regeneration of UDP-glucose (UDPG). RESULTS: The UDP-glucosyltransferase 85A1 (UGT85A1) from Arabidopsis thaliana, which showed high activity and regioselectivity towards tyrosol, was selected for the production of salidroside. Then, an in vitro cascade reaction for in situ regeneration of UDPG was constructed by coupling UGT85A1 to sucrose synthase from Glycine max (GmSuSy). The optimal UGT85A1-GmSuSy activity ratio of 1:2 was determined to balance the efficiency of salidroside production and UDP-glucose regeneration. Different cascade reaction conditions for salidroside production were also determined. Under the optimized condition, salidroside was produced at a titer of 6.0 g/L with a corresponding molar conversion of 99.6% and a specific productivity of 199.1 mg/L/h in a continuous feeding reactor. CONCLUSION: This is the highest salidroside titer ever reported so far using biocatalytic approach.

Neofunctionalization of a second insulin receptor gene in the wing-dimorphic planthopper, Nilaparvata lugens.

A single insulin receptor (InR) gene has been identified and extensively studied in model species ranging from nematodes to mice. However, most insects possess additional copies of InR, yet the functional significance, if any, of alternate InRs is unknown. Here, we used the wing-dimorphic brown planthopper (BPH) as a model system to query the role of a second InR copy in insects. NlInR2 resembled the BPH InR homologue (NlInR1) in terms of nymph development and reproduction, but revealed distinct regulatory roles in fuel metabolism, lifespan, and starvation tolerance. Unlike a lethal phenotype derived from NlInR1 null, homozygous NlInR2 null mutants were viable and accelerated DNA replication and cell proliferation in wing cells, thus redirecting short-winged-destined BPHs to develop into long-winged morphs. Additionally, the proper expression of NlInR2 was needed to maintain symmetric vein patterning in wings. Our findings provide the first direct evidence for the regulatory complexity of the two InR paralogues in insects, implying the functionally independent evolution of multiple InRs in invertebrates.

Vestigial mediates the effect of insulin signaling pathway on wing-morph switching in planthoppers.

Wing polymorphism is an evolutionary feature found in a wide variety of insects, which offers a model system for studying the evolutionary significance of dispersal. In the wing-dimorphic planthopper Nilaparvata lugens, the insulin/insulin-like growth factor signaling (IIS) pathway acts as a 'master signal' that directs the development of either long-winged (LW) or short-winged (SW) morphs via regulation of the activity of Forkhead transcription factor subgroup O (NlFoxO). However, downstream effectors of the IIS-FoxO signaling cascade that mediate alternative wing morphs are unclear. Here we found that vestigial (Nlvg), a key wing-patterning gene, is selectively and temporally regulated by the IIS-FoxO signaling cascade during the wing-morph decision stage (fifth-instar stage). RNA interference (RNAi)-mediated silencing of Nlfoxo increase Nlvg expression in the fifth-instar stage (the last nymphal stage), thereby inducing LW development. Conversely, silencing of Nlvg can antagonize the effects of IIS activity on LW development, redirecting wing commitment from LW to the morph with intermediate wing size. In vitro and in vivo binding assays indicated that NlFoxO protein may suppress Nlvg expression by directly binding to the first intron region of the Nlvg locus. Our findings provide a first glimpse of the link connecting the IIS pathway to the wing-patterning network on the developmental plasticity of wings in insects, and help us understanding how phenotypic diversity is generated by the modification of a common set of pattern elements.

Directional Growth and Density Modulation of Single-Atom Platinum for Efficient Electrocatalytic Hydrogen Evolution.

Dispersion of single atoms (SAs) in the host is important for optimizing catalytic activity. Herein, we propose a novel strategy to tune oxygen vacancies in CeO2-X directionally anchoring the single atom platinum (PtSA), which is uniformly dispersed on the rGO. The catalyst's performance for the hydrogen evolution reaction (HER) can be enhanced by controlling different densities of CeO2-X in rGO. The PtSA performs best optimally densified and loaded on homogeneous and moderately densified CeO2-X/rGO (PtSA-M-CeO2-X/rGO). It exhibited high activity in HER with an overpotential of 25 mV at 0.5 M H2SO4 and 33 mV at 1 KOH than that of almost reported electrocatalysts. Furthermore, it exhibited stability for 90 hours at -100 mA cm-2 in 1 KOH and -150 mA cm-2 in 0.5 M H2SO4 conditions, respectively. Through comprehensive experiments and theoretical calculations, the suitable dispersion density of PtSA on the defects of CeO2-X with more active sites gives the potential for practical applications. This research paves the way for developing single-atom catalysts with exceptional catalytic activity and stability, holding promise in advanced green energy conversion through defects engineering.

Tunable dissipative soliton Tm-doped fiber laser operating from 1700 nm to 1900 nm.

In this Letter, we demonstrate an ultrabroadband (1700-1900 nm) tunable Tm-doped fiber laser (TDFL) generating dissipative solitons in the net-normal dispersion regime. The laser delivers pulses with spectral widths ranging from 10 nm to 23 nm and pulse durations from 8.7 ps to 18.3 ps. Stretched-free pulse amplification at the gain edge (1708 nm) and gain peak (1807 nm) is implemented to demonstrate the range of further power scalability of the laser signal. The maximum achieved power in a one-stage Tm-doped amplifier is 140 mW with a compressed pulse duration of 478 fs. Considering the diverse utility of this wavelength band, this laser is highly desirable for applications such as optical sensing, biological imaging, and industrial machining.

Abdominal fat and muscle distributions in different stages of colorectal cancer.

BACKGROUND: The purpose of this study is to explore the difference of abdominal fat and muscle composition, especially subcutaneous and visceral adipose tissue, in different stages of colorectal cancer (CRC). MATERIALS AND METHODS: Patients were divided into 4 groups: healthy controls (patients without colorectal polyp), polyp group (patients with colorectal polyp), cancer group (CRC patients without cachexia), and cachexia group (CRC patients with cachexia). Skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) were assessed at the third lumbar level on computed tomography images obtained within 30 days before colonoscopy or surgery. One-way ANOVA and linear regression were used to analyze the difference of abdominal fat and muscle composition in different stages of CRC. RESULTS: A total of 1513 patients were divided into healthy controls, polyp group, cancer group, and cachexia group, respectively. In the development of CRC from normal mucosa to polyp and cancer, the VAT area of the polyp group was significantly higher than that of the healthy controls both in male (156.32 ± 69.71 cm2 vs. 141.97 ± 79.40 cm2, P = 0.014) and female patients (108.69 ± 53.95 cm2 vs. 96.28 ± 46.70 cm2, P = 0.044). However, no significant differences were observed of SAT area between polyp group and healthy controls in both sexes. SAT area decreased significantly in the male cancer group compared with the polyp group (111.16 ± 46.98 cm2 vs. 126.40 ± 43.52 cm2, P = 0.001), while no such change was observed in female patients. When compared with healthy controls, the SM, IMAT, SAT, and VAT areas of cachexia group was significantly decreased by 9.25 cm2 (95% CI: 5.39-13.11 cm2, P < 0.001), 1.93 cm2 (95% CI: 0.54-3.32 cm2, P = 0.001), 28.84 cm2 (95% CI: 17.84-39.83 cm2, P < 0.001), and 31.31 cm2 (95% CI: 18.12-44.51 cm2, P < 0.001) after adjusting for age and gender. CONCLUSION: Abdominal fat and muscle composition, especially SAT and VAT, was differently distributed in different stages of CRC. It is necessary to pay attention to the different roles of subcutaneous and visceral adipose tissue in the development of CRC.

Salvage peroral endoscopic myotomy is a promising treatment for achalasia after myotomy failure.

BACKGROUND AND AIMS: Reintervention modalities after myotomy failure in achalasia patients have yet to be established. The efficacy and safety of salvage peroral endoscopic myotomy (POEM) for treatment of achalasia after myotomy failure were evaluated in the study. METHODS: Between August 2011 and August 2021 at the Endoscopy Center of Zhongshan Hospital, 219 achalasia patients who had previously undergone a myotomy underwent a salvage POEM and were thus retrospectively enrolled in this study. After propensity score matching (PSM), operation-related parameters were compared between the salvage POEM group and the naïve POEM group. Subgroup analysis was performed between patients with previous Heller myotomy (HM) and patients with previous POEM. RESULTS: With similar baseline characteristics between both groups after PSM, the salvage POEM group presented with shorter tunnel length (11.8 ± 2.2 cm vs 12.8 ± .9 cm, P < .0001) and myotomy length (9.8 ± 2.0 cm vs 10.4 ± 1.0 cm, P < .0001) than the naïve POEM group. No significant differences were found in procedure-related adverse events between patients of salvage POEM and naïve POEM. The primary outcome of treatment success occurred in 175 of 193 patients (90.7%) in the salvage POEM group versus 362 of 374 patients (96.8%) in the naïve POEM group (P = .0046). At a 2- and 5-year follow-up, significantly higher rates of clinical failures were observed in the previous HM subgroup than in the previous POEM subgroup (P = .0433 and P = .0230, respectively). CONCLUSIONS: Salvage POEM after a previous myotomy failure, especially after a POEM failure, is a promising treatment option because it has a durable clinical relief rate.

Physiologically Based Pharmacokinetic Modeling for Multiple Oral Administration Labetalol in Pregnant Women.

BACKGROUND: Labetalol has an irreplaceable role in treating Hypertensive disorders of pregnancy (HDP), a common disease during pregnancy with a prevalence of 5.2-8.2%. However, there were big differences in dosage regimens between various guidelines. PURPOSE: A physiologically-based pharmacokinetics (PBPK) model was established and validated to evaluate the existing oral dosage regimens, and to compare the difference in plasma concentration between pregnant and non-pregnant women. METHODS: First, non-pregnant woman models with specific plasma clearance or enzymatic metabolism (UGT1A1, UGT2B7, CYP2C19) were established and validated. For CYP2C19, slow, intermediate, and rapid metabolic phenotypes were considered. Then, a pregnant model with proper structure and parameters adjustment was established and validated against the multiple oral administration data. RESULTS: The predicted labetalol exposure captured the experimental data well. The following simulations with criteria lowering 15 mmHg blood pressure (corresponding to around 108 ng/ml plasma labetalol) found that the maximum daily dosage in the Chinese guideline may be insufficient for some severe HDP patients. Moreover, similar predicted steady-state trough plasma concentration was found between the maximum daily dosage in the American College of Obstetricians and Gynecologists (ACOG) guideline, 800 mg Q8h and a regimen of 200 mg Q6h. Simulations comparing non-pregnant and pregnant women found that the difference in labetalol exposure highly depended on the CYP2C19 metabolic phenotype. CONCLUSIONS: In summary, this work initially established a PBPK model for multiple oral administration of labetalol for pregnant women. This PBPK model may lead to personalized labetalol medication in the future.

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives.

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

A prediction model and nomogram for technical difficulty of peroral endoscopic myotomy.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a promising endoscopic technique for achalasia. We aimed to establish a regression model and develop a simple nomogram to predict the technical difficulty of POEM in a single center with large volume cases. METHODS: 3385 achalasia patients treated with POEM were included, and the technical difficulty was systemically evaluated. All of them were randomized into the training cohort (n = 1693) or internal validation cohort (n = 1692). Then, the prediction model and nomogram were proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. RESULTS: Of 3385 patients, technical difficulty happened in 417 (12.32%) cases. In the training stage, six factors were weighted based on the ß coefficient from the regression model, including age, disease duration, sigmoid esophagus, mucosal edema, submucosal fibrosis, and tunnel length. The patients were categorized into low-risk (< 0.1), medium-risk (0.1-0.25), and high-risk (> = 0.25) groups. Our score model performed satisfying discrimination with the areas under the receiver-operating characteristic curve (AUC) of 0.743 (95% confidence interval (CI), 0.701-0.785) and calibration with goodness of fit in the Hosmer-Lemeshow test (P = 0.088) in internal validation. CONCLUSIONS: The prediction model and nomogram demonstrated good performance in predicting the technical difficulty of POEM.

Rotational energy transfer in the collision of N2O with He atom.

The quantum state-to-state rotationally inelastic quenching of N2O by colliding with a He atom is studied on an ab initio potential energy surface with N2O lying on its vibrational ground state. The cross sections for collision energies from 10-6-100 cm-1 and rate constants from 10-5-10 K are calculated employing the fully converged quantum close-coupling method for the quenching of the j = 1-6 rotational states of N2O. Numerous van der Waals shapes or Feshbach resonances are observed; the cross sections of different channels are found to follow the Wigner scaling law in the cold threshold regime and may intersect with each other. In order to interpret the mechanism and estimate the cross sections of the rotational energy transfer, we propose a minimal classical model of collision between an asymmetric double-shell ellipsoid and a point particle. The classical model reproduces the quantum scattering results and points out the attractive interactions and the potential asymmetry can affect the collision process. The resulting insights are expected to expand our interpretations of inelastic scattering and energy transfer in molecular collisions.

In-hospital nursing care intervention increasing the effect of vacuum sealing drainage on wound healing: A meta-analysis.

Vacuum sealing drainage (VSD) could effectively drain superficial wounds and deep tissues, which is beneficial for wound healing. More incentives in nursing care to improve the therapeutic effect of VSD on wound healing were further investigated. Different databases were retrieved for full-text publications about the comparison between intervention nursing care and regular nursing care. Heterogeneity was detected by I2 method, and a random-effect model was applied for data pooling if there existed heterogeneity. Publication bias was analysed by a funnel plot. Eight studies with 762 patients were included for final meta-analysis. In the nursing care intervention group, shorter hospital stay duration (pooled SMD = -2.602, 95% confidence interval: -4.052--1.151), shorter wound healing time (pooled SMD = -1.105, 95% confidence interval: -1.857--0.353), lower pain score (pooled SMD = -2.490, 95% confidence interval: -3.521--1.458), lower drainage tube blocked rate (pooled RR = 0.361, 95% confidence interval: 0.268-0.486), and higher nursing satisfaction (pooled RR = 1.164, 95% confidence interval: 1.095-1.237) was confirmed. More active and incentive nursing care could significantly improve the therapeutic effect of VSD on wound healing, in terms of hospitalisation time, wound healing time, painful symptoms, drainage tube blockage, and nursing satisfaction.

Fiber tracing and microstructural characterization among audiovisual integration brain regions in neonates compared with young adults.

Audiovisual integration has been related with cognitive-processing and behavioral advantages, as well as with various socio-cognitive disorders. While some studies have identified brain regions instantiating this ability shortly after birth, little is known about the structural pathways connecting them. The goal of the present study was to reconstruct fiber tracts linking AVI regions in the newborn in-vivo brain and assess their adult-likeness by comparing them with analogous fiber tracts of young adults. We performed probabilistic tractography and compared connective probabilities between a sample of term-born neonates (N = 311; the Developing Human Connectome Project (dHCP, http://www.developingconnectome.org) and young adults (N = 311 The Human Connectome Project; https://www.humanconnectome.org/) by means of a classification algorithm. Furthermore, we computed Dice coefficients to assess between-group spatial similarity of the reconstructed fibers and used diffusion metrics to characterize neonates' AVI brain network in terms of microstructural properties, interhemispheric differences and the association with perinatal covariates and biological sex. Overall, our results indicate that the AVI fiber bundles were successfully reconstructed in a vast majority of neonates, similarly to adults. Connective probability distributional similarities and spatial overlaps of AVI fibers between the two groups differed across the reconstructed fibers. There was a rank-order correspondence of the fibers' connective strengths across the groups. Additionally, the study revealed patterns of diffusion metrics in line with early white matter developmental trajectories and a developmental advantage for females. Altogether, these findings deliver evidence of meaningful structural connections among AVI regions in the newborn in-vivo brain.

Abdominal-B contributes to abdominal identity in the brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

The homeotic complex gene Abdominal-B (Abd-B) is involved in regulating the development of posterior abdomens and has been extensively studied in holometabolous insects. However, the function of Abd-B in hemimetabolous insects is not fully understood. Here, we functionally characterize an Abd-B homologue in the brown planthopper (BPH), Nilaparvata lugens. The full-length cDNA of the N. lugens Abd-B homologue (NlAbd-B) is 2334 nt, with an open reading frame of 1113 bp. NlAbd-B has the highest expression level at the egg stage relative to the nymphal and adult stages and is mainly expressed in the fourth to the ninth abdominal segment of embryos. RNA interference (RNAi)-mediated knockdown of NlAbd-B in nymphs disrupted the development of genitalia both in females and males and caused a genitalia-to-leg transformation. Parental RNAi of NlAbd-B in both female and male adults caused an extra abdominal segment in offspring nymphs, while parental RNAi of the N. lugens abdominal-A homologue in both female and males adults led to embryos with leg-like appendages on the second to the eighth abdominal segment. These findings suggest that NlAbd-B plays a pivotal role in genital development and posterior abdominal patterning and thus highlight the conservational role of Abd-B in holometabolous and hemimetabolous insects.

Midazolam exhibits antitumour and enhances the efficiency of Anti-PD-1 immunotherapy in hepatocellular carcinoma.

BACKGROUND: Midazolam (MDZ) is an anaesthetic that is widely used for anxiolysis and sedation. More recently, MDZ has also been described to be related to the outcome of various types of carcinomas. However, how MDZ influences the progression of hepatocellular carcinoma (HCC) and its effects on the biological function and tumour immune microenvironment of this type of tumour remain unknown. METHODS: The effects of MDZ on the proliferation, invasion, and migration of HCC cell lines were examined in vitro using the Cell Counting Kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), Transwell, and wound healing assays. Additionally, western blotting was employed to confirm that PD-L1 was expressed. Chromatin immunoprecipitation-seq (ChIP-seq) analysis was used to pinpoint the transcriptional regulation regions of NF-κB and programmed death-ligand 1 (PD-L1). A C57BL/6 mouse model was used to produce subcutaneous HCC tumors in order to evaluate the in vivo performance of MDZ. Mass spectrometry was also used to assess changes in the tumour immunological microenvironment following MDZ injection. RESULTS: The HCC-LM3 and Hep-3B cell lines' proliferation, invasion, and migration were controlled by MDZ, according to the results of the CCK8, EdU, Transwell, and wound healing assays. PD-L1 expression was shown by ChIP-seq analysis to be boosted by NF-κB, and by Western blotting analysis, it was shown that MDZ downregulated the expression of NF-κB. Additionally, in vivo tests revealed that intraperitoneal MDZ injections reduced HCC tumor development and enhanced the effectiveness of anti-PD-1 therapy. The CD45+ immune cell proportions were higher in the MDZ group than in the PBS group, according to the mass spectrometry results. Injection of MDZ resulted in a decrease in the proportions of CD4+ T cells, CD8+ T cells, natural killer (NK) cells, monocytes, Tregs, and M2 macrophages and a rise in the proportion of dendritic cells. Additionally, the concentrations of the cytokines IFN-g and TNF-a were noticeably raised whereas the concentrations of the CD8+ T-cell fatigue markers ICOS, TIGIT, and TIM3 were noticeably lowered. CONCLUSION: According to this study, MDZ inhibited the progression of HCC by inhibiting the NF-κB pathway and reducing the exhaustion of CD8+ T cells. In clinical practice, MDZ combined with anti-PD-1 therapy might contribute to synergistically improving the antitumor efficacy of HCC treatment.