Dominance complementation of parental heading date alleles of Hd1, Ghd7, DTH8, and PRR37 confers transgressive late maturation in hybrid rice.

Rice (Oryza sativa L.) is a short-day plant whose heading date is largely determined by photoperiod sensitivity (PS). Many parental lines used in hybrid rice breeding have weak PS, but their F1 progenies have strong PS and exhibit an undesirable transgressive late-maturing phenotype. However, the genetic basis for this phenomenon is unclear. Therefore, effective methods are needed for selecting parents to create F1 hybrid varieties with the desired PS. In this study, we used bulked segregant analysis with F1 Ningyou 1179 (strong PS) and its F2 population, and through analyzing both parental haplotypes and PS data for 918 hybrid rice varieties, to identify the genetic basis of transgressive late maturation which is dependent on dominance complementation effects of Hd1, Ghd7, DTH8, and PRR37 from both parents rather than from a single parental genotype. We designed a molecular marker-assisted selection system to identify the genotypes of Hd1, Ghd7, DTH8, and PRR37 in parental lines to predict PS in F1 plants prior to crossing. Furthermore, we used CRISPR/Cas9 technique to knock out Hd1 in Ning A (sterile line) and Ning B (maintainer line) and obtained an hd1-NY material with weak PS while retaining the elite agronomic traits of NY. Our findings clarified the genetic basis of transgressive late maturation in hybrid rice and developed effective methods for parental selection and gene editing to facilitate the breeding of hybrid varieties with the desired PS for improving their adaptability.

High-throughput solutions in tumor organoids: From culture to drug screening.

Tumor organoids have emerged as an ideal in vitro model for patient-derived tissues, as they recapitulate the characteristics of the source tumor tissue to a certain extent, offering the potential for personalized tumor therapy and demonstrating significant promise in pharmaceutical research and development. However, establishing and applying this model involves multiple labor-intensive and time-consuming experimental steps and lacks standardized protocols and uniform identification criteria. Thus, high-throughput solutions are essential for the widespread adoption of tumor organoid models. This review provides a comprehensive overview of current high-throughput solutions across the entire workflow of tumor organoids, from sampling and culture to drug screening. Furthermore, we explore various technologies that can control and optimize single-cell preparation, organoid culture, and drug screening with the ultimate goal of ensuring the automation and high efficiency of the culture system and identifying more effective tumor therapeutics.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Safety and efficacy of stoma site selection in CT-guided percutaneous gastrostomy: a retrospective analysis.

PURPOSE: To compare the safety and efficacy of CPG in the rectus abdominis and intercostal regions. MATERIALS AND METHODS: This retrospective study included 226 patients who underwent CPG at a single center, with the stoma placed in the rectus abdominis or intercostal region. Surgical outcomes and complications, such as pain and infection within 6 months postoperatively, were recorded. RESULTS: The surgical success rate was 100%, and the all-cause mortality rate within 1 month was 0%. An intercostal stoma was placed in 56 patients; a rectus abdominis stoma was placed in 170 patients. The duration of surgery was longer for intercostal stoma placement (37.66 ± 14.63 min) than for rectus abdominis stoma placement (30.26 ± 12.40 min) (P = 0.000). At 1 month postsurgery, the rate of stoma infection was greater in the intercostal group (32.1%) than in the rectus abdominis group (20.6%), but the difference was not significant (P = 0.077). No significant difference was observed in the infection rate between the two groups at 3 or 6 months postsurgery (P > 0.05). Intercostal stoma patients reported higher pain scores during the perioperative period and at 1 month postsurgery (P = 0.000), but pain scores were similar between the two groups at 3 and 6 months postsurgery. The perioperative complication rates for intercostal and rectus abdominis surgery were 1.8% and 5.3%, respectively (P = 0.464), with no significant difference in the incidence of tube dislodgement (P = 0.514). Patient weight improved significantly at 3 and 6 months postoperatively compared to preoperatively (P < 0.05). CONCLUSION: Rectus abdominis and intercostal stomas have similar safety and efficacy. However, intercostal stomas may result in greater short-term patient discomfort.

Early cumulus cell removal increases cumulative live birth rate while having no negative effect on the malformation rate in in vitro fertilization: a propensity score-matched cohort study.

PURPOSE: The aim of this study was to investigate the efficacy and safety of early cumulus cell removal (ECCR) during human in vitro fertilization (IVF). METHODS: A retrospective analysis was performed between January 2011 and December 2019. The study enrolled 1131 couples who underwent IVF treatment with ECCR. After propensity score matching at a 1:1 ratio, 1131 couples who underwent overnight coincubation of gametes were selected. The main outcome measure was the cumulative live birth rate. Secondary outcome measures included the cumulative pregnancy rate, polyspermy rate, available embryo rate, miscarriage rate, malformation rate, time to live birth, and oocyte-to-baby rate. RESULTS: There were no significant differences found between the two groups in the polyspermy rate, available embryo rate, miscarriage rate, time to live birth, oocyte-to-baby rate, and neonatal congenital anomalies rate. The results of the study showed that ECCR was associated with a significantly higher cumulative live birth rate and cumulative pregnancy rate, along with a significantly lower fertilization rate. CONCLUSIONS: ECCR tended to confer increased cumulative live birth rate and had no negative effect on the neonatal malformation rate.

Altered Response Pattern following AZD5582 Treatment of SIV-Infected, ART-Suppressed Rhesus Macaque Infants.

The "shock and kill" strategy for HIV-1 cure incorporates latency-reversing agents (LRA) in combination with interventions that aid the host immune system in clearing virally reactivated cells. LRAs have not yet been investigated in pediatric clinical or preclinical studies. Here, we evaluated an inhibitor of apoptosis protein (IAP) inhibitor (IAPi), AZD5582, that activates the noncanonical NF-κB (ncNF-κB) signaling pathway to reverse latency. Ten weekly doses of AZD5582 were intravenously administered at 0.1 mg/kg to rhesus macaque (RM) infants orally infected with SIVmac251 at 4 weeks of age and treated with a triple ART regimen for over 1 year. During AZD5582 treatment, on-ART viremia above the limit of detection (LOD, 60 copies/mL) was observed in 5/8 infant RMs starting at 3 days post-dose 4 and peaking at 771 copies/mL. Of the 135 measurements during AZD5582 treatment in these 5 RM infants, only 8 were above the LOD (6%), lower than the 46% we have previously reported in adult RMs. Pharmacokinetic analysis of plasma AZD5582 levels revealed a lower Cmax in treated infants compared to adults (294 ng/mL versus 802 ng/mL). RNA-Sequencing of CD4+ T cells comparing pre- and post-AZD5582 dosing showed many genes that were similarly upregulated in infants and adults, but the expression of key ncNF-κB genes, including NFKB2 and RELB, was significantly higher in adult RMs. Our results suggest that dosing modifications for this latency reversal approach may be necessary to maximize virus reactivation in the pediatric setting for successful "shock and kill" strategies. IMPORTANCE While antiretroviral therapy (ART) has improved HIV-1 disease outcome and reduced transmission, interruption of ART results in rapid viral rebound due to the persistent latent reservoir. Interventions to reduce the viral reservoir are of critical importance, especially for children who must adhere to lifelong ART to prevent disease progression. Here, we used our previously established pediatric nonhuman primate model of oral SIV infection to evaluate AZD5582, identified as a potent latency-reversing agent in adult macaques, in the controlled setting of daily ART. We demonstrated the safety of the IAPi AZD5582 and evaluate the pharmacokinetics and pharmacodynamics of repeated dosing. The response to AZD5582 in macaque infants differed from what we previously showed in adult macaques with weaker latency reversal in infants, likely due to altered pharmacokinetics and less inducibility of infant CD4+ T cells. These data supported the contention that HIV-1 cure strategies for children are best evaluated using pediatric model systems.

A visual defect detection for optics lens based on the YOLOv5 -C3CA-SPPF network model.

Defects in the optical lens directly affect the scattering properties of the optical lens and decrease the performance of the optical element. Although machine vision instead of manual detection has been widely valued, the feature fusion technique of series operation and edge detection cannot recognize low-contrast and multi-scale targets in the lens. To address these challenges, in this study, an improved YOLOv5-C3CA-SPPF network model is proposed to detect defects on the surface and inside of the lens. The hybrid module combining the coordinate attention and CSPNet (C3) is incorporated into YOLOv5-C3CA for improving the extraction of target feature information and detection accuracy. Furthermore, an SPPF features fusion module is inserted into the neck of the network model to improve the detection accuracy of the network. To enhance the performance of supervised learning algorithms, a dataset containing a total of 3800 images is created, more than 600 images for each type of defect samples. The outcome of the experiment manifests that the mean average precision (mAP) of the YOLOv5-C3CA-SPPF algorithm is 97.1%, and the detection speed FPS is 41 f/s. Contrast to the traditional lens surface defects detection algorithms, YOLOv5-C3CA-SPPF can detect the types of optical lens surface and inside defects more accurately and quickly, the experimental results show that the YOLOv5-C3CA-SPPF model for identifying optical lens defects has good generalizability and robustness, which is favorable for on-line quality automatic detection of optical lens defects and provide an important guarantee for the quality consistency of finished products.

P T symmetry in a superconducting hybrid quantum system with longitudinal coupling.

We propose a scheme consisting of coupled nanomechanical cantilever resonators and superconducting flux qubits to engineer a parity-time- (P T-) symmetric phononic system formed by active and passive modes. The effective gain (loss) of the phonon mode is achieved by the longitudinal coupling of the resonator and the fast dissipative superconducting qubit with a blue-sideband driving (red-sideband driving). A P T-symmetric to broken-P T-symmetric phase transition can be observed in both balanced gain-to-loss and unbalanced gain-to-loss cases. Applying a resonant weak probe field to the dissipative resonator, we find that (i) for balanced gain and loss, the acoustic signal absorption to amplification can be tuned by changing the coupling strength between resonators; (ii) for unbalanced gain and loss, both acoustically induced transparency and anomalous dispersion can be observed around Δ = 0, where the maximum group delay is also located at this point. Our work provides an experimentally feasible scheme to design P T-symmetric phononic systems and a powerful platform for controllable acoustic signal transmission in a hybrid quantum system.

A self-powered sound-driven humidity sensor for wearable intelligent dehydration monitoring system.

Self-powered wearable sensing systems have attracted great attention for their application in continuous health monitoring, which can reveal real-time physiological information on the body. Here, an innovative self-powered sound-driven humidity sensor for wearable intelligent dehydration monitoring system has been proposed. The sensor is primarily comprised of PTFE membrane, ZnO nanoarrays and Ti thin film. The piezoelectric/triboelectric effect of ZnO nanoarrays/PTFE membrane is coupled with the humidity sensing process. Sound wave can drive PTFE membrane to vibrate, and the contact and separation between PTFE and ZnO can generate electrical signals through piezoelectric/triboelectric effect. At the same time, the surface of the nanostructures can absorb the water molecules, which will influence the electrical output of the device. The device can convert sound energy into electrical output without any external electricity power supply, and the outputting voltage decreases with increasing relative humidity, acting as the sensing signal. The sensor has been integrated with data processing unit and wireless transmission module to form a self-powered wearable intelligent dehydration monitoring system, which can actively monitor the humidity of exhaled breath and transmit the information to the mobile phone. The results can open a possible new direction for the development of sound-driven gas sensors and will further expand the scope for self-powered nanosystems.

Recombinant Klotho attenuates IFNγ receptor signaling and SAMHD1 expression through blocking NF-κB translocation in glomerular mesangial cells.

Interferon gamma (IFNγ) is a cytokine implicated in the pathogenesis of autoimmune diseases. SAM and HD domain-containing protein 1 (SAMHD1) is an IFNγ-inducible protein that modulates cellular dNTP levels. Mutations in the human SAMHD1 gene cause Aicardi-Goutières (AG) syndrome, an autoimmune disease sharing similar clinical features with systemic lupus erythematosus (SLE). Klotho is an anti-inflammatory protein which suppresses aging through multiple mechanisms. Implication of Klotho in autoimmune response is identified in rheumatologic diseases such as SLE. Little information exists regarding the effect of Klotho in lupus nephritis, one of the prevalent symptoms of SLE. The present study verified the effect of IFNγ on SAMHD1 and Klotho expression in MES-13 glomerular mesangial cells, a special cell type in glomerulus that is critically involved in lupus nephritis. IFNγ upregulated SAMHD1 expression in MES-13 cells through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT1) and the nuclear factor kappa B (NFκB) signaling pathways. IFNγ decreased Klotho protein expression in MES-13 cells. Treatment of MES-13 cells with recombinant Klotho protein inhibited SAMHD1 expression by blocking IFNγ-induced NFκB nuclear translocation, but showed no effect on JAK-STAT1 signaling. Collectively, our findings support the protective role of Klotho in attenuating lupus nephritis through the inhibition of IFNγ-induced SAMHD1 expression and IFNγ downstream signaling in MES-13 cells.

Improved STMask R-CNN-based defect detection model for automatic visual inspection of an optics lens.

A lens defect is a common quality issue that has seriously harmed the scattering characteristics and performance of optical elements, reducing the quality consistency of the finished products. Furthermore, the energy hotspots coming from the high-energy laser through diffraction of optical component defects are amplified step by step in multi-level laser conduction, causing serious damage to the optical system. Traditional manual detection mainly relies on experienced workers under a special light source environment with high labor intensity, low efficiency, and accuracy. The common machine vision techniques are incapable of detecting low contrast and complex morphological defects. To address these challenges, a deep learning-based method, named STMask R-CNN, is proposed to detect defects on the surface and inside of a lens in complex environments. A Swin Transformer, which focuses on improving the modeling and representation capability of the features in order to improve the detection performance, is incorporated into the Mask R-CNN in this case. A challenge dataset containing more than 3800 images (18000 defect sample targets) with five different types of optical lens defects was created to verify the proposed approach. According to our experiments, the presented STMask R-CNN reached a precision value of 98.2%, recall value of 97.7%, F1 score of 97.9%, mAP@0.5 value of 98.1%, and FPS value of 24 f/s, which outperformed the SSD, Faster R-CNN, and YOLOv5. The experimental results demonstrated that the proposed STMask R-CNN outperformed other popular methods for multiscale targets, low contrast target detection and nesting, stacking, and intersecting defects sample detection, exhibiting good generalizability and robustness, as well as detection speed to meet mechanical equipment production efficiency requirements. In general, this research offers a favorable deep learning-based method for real-time automatic detection of optical lens defects.

Treatment of obstructive sleep apnea with a simple CPAP device.

PURPOSE: CPAP is the "gold standard" treatment for obstructive sleep apnea (OSA). Current CPAP models have developed additional functions including automatic CPAP and pressure relief. However, CPAP adherence has not improved over the last three decades. Many patients in low-income countries cannot afford these CPAP devices. A novel simple CPAP device with a fixed pressure without pressure controller was developed. METHODS: Manual CPAP pressure titration was performed in 127 patients with OSA. Six patients with a titration pressure higher than 11 cmH2O and 14 patients who could not tolerate CPAP were excluded, leaving 107 participating in the following 2 studies. In study one, 54 of 107 patients were treated by both conventional fixed CPAP and simple CPAP in random order. In the second study, another 53 patients were treated by both autoCPAP in automatic function and simple CPAP in random order. Simple CPAP was fixed at 10 cmH2O, 8 cmH2O, and 6 cmH2O for patients whose titration pressure was between 9-10, 7-8, and ≤ 6 cmH2O, respectively. Conventional fixed CPAP device was set exactly the same as manual titration pressure. RESULTS: All patients whose manual titration pressure ≤ 10 cmH2O were effectively treated by simple CPAP (AHI 40.7 ± 2.3 events/h before vs 2.5 ± 0.3 events/h after, p < 0.001). Patients expressed similar preferences for simple CPAP, autoCPAP, and conventional fixed CPAP (p > 0.05). CONCLUSIONS: We conclude that a novel simple CPAP is an alternative treatment for most patients with OSA, which may widen access to CPAP therapy in the developing countries because of its low cost.

The preparation, characterization, and application of porous core-shell composite particles produced with laboratory-scale spray dryer.

OBJECTIVE: To prepare porous core-shell composite particles (PCPs) in order to improve the flowability and compactibility of powder materials for direct compaction (DC), as well as the dissolution of tablets. SIGNIFICANCE: The results obtained are meaningful to boosting the development and further research of PCPs on DC. Methods: In this study, hydroxypropyl methylcellulose (HPMC E3) and polyvinylpyrrolidone (PVP K30) were selected as shell materials, the Xiao Er Xi Shi formulation powder (XEXS) was used as the core materials, ammonium bicarbonate (NH4HCO3), and sodium bicarbonate (NaHCO3) were employed as pore-forming agent. Using co-spray drying method to prepare composite particles (CPs). Then, the physical properties and comparison between different CPs were characterized comprehensively. Finally, the different CPs were directly compacted as tablets to explore the effect on the dissolution behavior of DC tablets, respectively. RESULTS: (i) The XEXS PCPs were prepared successfully by co-spray drying, and the yield of PCPs is almost 80%; (ii) The TS values of PCP-X-P-Na, PCP-X-P-NH4, PCP-X-H-Na and PCP-X-P-Na were 5.70, 7.56, 3.98, and 6.88 times higher than that of raw material (X); (iii) The disintegration time of PCPs tablets decreased 10-25% when compared with CPs tablets; (iv) The values of Carr's index (CI), Hausner ratio (HR), Caking strength (CS), and Cohesion index (CoI) of PCP-X-H-NH4 were 19.16%, 19.29%, 40.14%, and 6.39% lower than that of X, respectively. CONCLUSIONS: The PCPs prepared by co-spray drying did improve the flowability and compactibility of powder, as well as the dissolution of tablets.

Effect of Lacking ZKSCAN3 on Autophagy, Lysosomal Biogenesis and Senescence.

Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagic and lysosomal genes. As a member of the zinc finger family DNA-binding proteins, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induce autophagy and promote lysosomal biogenesis in cancer cells. However, studies in Zkscan3 knockout mice showed that the deficiency of ZKSCAN3 did not induce autophagy or increase lysosomal biogenesis. In order to further explore the role of ZKSCAN3 in the transcriptional regulation of autophagic genes in human cancer and non-cancer cells, we generated ZKSCAN3 knockout HK-2 (non-cancer) and Hela (cancer) cells via the CRISPR/Cas9 system and analyzed the differences in gene expression between ZKSCAN3 deleted cells and non-deleted cells through fluorescence quantitative PCR, western blot and transcriptome sequencing, with special attention to the differences in expression of autophagic and lysosomal genes. We found that ZKSCAN3 may be a cancer-related gene involved in cancer progression, but not an essential transcriptional repressor of autophagic or lysosomal genes, as the lacking of ZKSCAN3 cannot significantly promote the expression of autophagic and lysosomal genes.

HER2 induces cell scattering and invasion through ∆Np63α and E-cadherin.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer constitutes approximately 30% of human breast cancers and is associated with poor outcomes. ∆Np63 is considered a metastasis inhibitor involved with cancer progression. This study aimed to clarify the roles and mechanisms of HER2 and ∆Np63 on scattering and invasion of MCF10A cells. Wild-type or mutant HER2 was cloned and transfected into MCF10A cells. Cell counting and transwell assays were applied to unveil the impact of HER2 upregulation and mutation on proliferation, cell scattering, and invasion. Western blotting and cell accounting were used to investigate the roles of ∆Np63 and p27. In vivo lung colonization assay was used to reveal the influences of HER2 and ∆Np63a on tumor metastasis. The results indicated HER2 remarkably enhanced cell proliferation, invasion, and scattering. Overexpression of either ΔNp63 or E-cadherin led to attenuated HER2-mediated regulation of cell migration, invasion, and scattering. Furthermore, we confirmed that HER2 enhanced cell proliferation but not migration through p27 and independent ∆Np63a. The results revealed that ∆Np63α contributed to the inhibition of HER2-induced metastasis. Collectively, our findings may further our understanding of the regulation of tumor progression and metastasis.

Natural allelic variation of GmST05 controlling seed size and quality in soybean.

Seed size is one of the most important agronomic traits determining the yield of crops. Cloning the key genes controlling seed size and pyramiding their elite alleles will facilitate yield improvement. To date, few genes controlling seed size have been identified in soybean, a major crop that provides half of the plant oil and one quarter of the plant protein globally. Here, through a genome-wide association study of over 1800 soybean accessions, we determined that natural allelic variation at GmST05 (Seed Thickness 05) predominantly controlled seed thickness and size in soybean germplasm. Further analyses suggested that the two major haplotypes of GmST05 differed significantly at the transcriptional level. Transgenic experiments demonstrated that GmST05 positively regulated seed size and influenced oil and protein contents, possibly by regulating the transcription of GmSWEET10a. Population genetic diversity analysis suggested that allelic variations of GmST05 were selected during geographical differentiation but have not been fixed. In summary, natural variation in GmST05 determines transcription levels and influences seed size and quality in soybean, making it an important gene resource for soybean molecular breeding.

CD8 lymphocyte depletion enhances the latency reversal activity of the SMAC mimetic AZD5582 in ART-suppressed SIV-infected rhesus macaques.

Inducing latency reversal to reveal infected cells to the host immune system represents a potential strategy to cure HIV infection. In separate studies, we have previously shown that CD8+ T cells may contribute to the maintenance of viral latency and identified a novel SMAC mimetic/IAP inhibitor (AZD5582) capable of reversing HIV/SIV latency in vivo by activating the non-canonical (nc) NF-κB pathway. Here, we use AZD5582 in combination with antibody-mediated depletion of CD8α+ cells to further evaluate the role of CD8+ T cells in viral latency maintenance. Six rhesus macaques (RM) were infected with SIVmac239 and treated with ART starting at week 8 post-infection. After 84-85 weeks of ART, all animals received a single dose of the anti-CD8α depleting antibody (Ab), MT807R1 (50mg/kg, s.c.), followed by 5 weekly doses of AZD5582 (0.1 mg/kg, i.v.). Following CD8α depletion + AZD5582 combined treatment, 100% of RMs experienced on-ART viremia above 60 copies per ml of plasma. In comparator groups of ART-suppressed SIV-infected RMs treated with AZD5582 only or CD8α depletion only, on-ART viremia was experienced by 56% and 57% of the animals respectively. Furthermore, the frequency of increased viremic episodes during the treatment period was greater in the CD8α depletion + AZD5582 group as compared to other groups. Mathematical modeling of virus reactivation suggested that, in addition to viral dynamics during acute infection, CD8α depletion influenced the response to AZD5582. This work suggests that the latency reversal induced by activation of the ncNF-κB signaling pathway with AZD5582 can be enhanced by CD8α+ cell depletion.

Ultra-strong optical four-wave mixing signal induced by strong exciton-phonon and exciton-plasmon couplings.

We propose a scheme to generate ultra-strong four-wave mixing (FWM) signal based on a suspended monolayer graphene nanoribbon nanomechanical resonator (NR) coupled to an Au nanoparticle (NP). It is shown that, the FWM spectrum can switch among two-peaked, three-peaked, four-peaked or five-peaked via the modulation of exciton-phonon and exciton-plasmon couplings. This is mainly attributed to the vibrational properties of NR related to the exciton-phonon coupling, and the energy-level splitting of the localized exciton correlated to three classes of resonances consisting of three-photon resonance, Rayleigh Resonance, and AC-Stark atomic resonance. Especially, in a dual-strong coupling regime, the gains for these peaks can be as high as nine orders of magnitude (∼ 109) around the lower bistable threshold due to a combined effect of two couplings. Our findings not only offer an efficient way to measure the vibrational frequency of NR and the exciton-phonon coupling strength but also provide a possibility to fabricate high-performance optoelectronic nanodevices.

Preparation and application of chitosan-based fluorescent probes.

Biomass materials have abundant natural resources, renewability and good biochemical compatibility, so biomass-based fluorescent materials prepared from biomass materials have gradually become a research hotspot. In particular, the low cost and environmentally friendly properties of chitosan have been widely used in the field of functional materials. Chitosan-based functional materials have attracted extensive attention in the detection and removal of organic and inorganic pollutants. They have been widely used in biological imaging, environmental detection, drug carriers and other fields. This paper reviews the preparation and application of chitosan-based fluorescent probes, including chitosan-derived fluorescent probe materials and chitosan-based carbon quantum dots. At the same time, it focuses on the application research of chitosan-based carbon quantum dots in the fields of environmental detection, cell imaging, drug carriers, photocatalysis, etc. In addition, it provides new ideas and application prospects for the development and application of chitosan-based fluorescent materials in the future.