Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

The effect of ultrasonic power on the physicochemical properties and antioxidant activities of frosted figs pectin.

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

Effect of hydrothermal treatment on the rheological properties of xanthan gum.

In this study, the effect of hydrothermal treatment with different temperatures (120-180 °C) on the rheological properties of xanthan gum was evaluated. When the temperature of hydrothermal treatment was relatively low (120 °C), the rheological properties of the hydrothermally treated xanthan gum was similar to the untreated xanthan gum (pseudoplastic and solid-like/gel-like behavior). However, as the temperature of hydrothermal treatment was higher, the rheological properties of the hydrothermally treated xanthan gum changed greatly (e.g., a wider range of Newtonian plateaus in flow curves, existence of a critical frequency between the storage modulus (G') and the loss modulus (G") in the dynamic viscoelasticity measurement, variation of complex viscosity). Although the hydrothermal treatment showed little influence on the functional groups of xanthan gum, it altered the micromorphology of xanthan gum from uneven and rough lump-like to thinner and smoother flake-like. In addition, higher concentration (2 %) of hydrothermally treated xanthan gum made its viscosity close to that of the untreated xanthan gum (1 %). Besides, hydrothermal treatment also affected the effect of temperature and salt (CaCl2) adding on the rheological properties of xanthan gum. Overall, this study can provide some useful information on the rheological properties of xanthan gum after hydrothermal treatment.

Mixed crushing and competitive leaching of all electrode material components and metal collector fluid in the spent lithium battery.

Hydrometallurgy is a primary method for recovering cathode electrode materials from spent lithium-ion batteries (LIBs). Most of the current research materials are pure cathode electrode materials obtained through manual disassembly. However, the spent LIBs are typically broken as a whole during the actual industrial recycling which makes the electrode materials combined with the collector fluid. Therefore, the competitive leaching between metal collector fluid and electrode material was examined. The pyrolysis characteristics of the electrode materials were analyzed to determine the pyrolysis temperature. The electrode sheet was pyrolyzed and then crushed for competitive leaching. The effect of pyrolysis was analyzed by XPS. The competitive leaching behavior was studied based on leaching agent concentration, leaching time and leaching temperature. The composition and morphology of the residue were determined to prove the competitive leaching results by XRD-SEM. TG results showed that 500 °C was the suitable pyrolysis temperature. XPS analysis demonstrated that pyrolysis can completely remove PVDF. Li and Co were preferentially leached during the competitive leaching while the leaching rates were 90.10% and 93.40% with 50 min leaching at 70 °C. The Al and Cu had weak competitive leachability and the leaching rate was 29.10% and 0.00%. XRD-SEM analysis showed that Li and Co can be fully leached with residual Al and Cu remaining. The results showed that the mixed leaching of electrode materials is feasible based on its excellent selective leaching properties.

Floquet Engineering the Exceptional Points in Parity-Time-Symmetric Magnonics.

Magnons serve as a testing ground for fundamental aspects of Hermitian and non-Hermitian wave mechanics and are of high relevance for information technology. This study presents setups for realizing spatiotemporally driven parity-time- (PT) symmetric magnonics based on coupled magnetic waveguides and magnonic crystals. A charge current in a metal layer with strong spin-orbit coupling sandwiched between two insulating magnetic waveguides leads to gain or loss in the magnon amplitude depending on the directions of the magnetization and the charge currents. When gain in one waveguide is balanced by loss in the other waveguide, a PT-symmetric system hosting non-Hermitian degeneracies [or exceptional points (EPs)] is realized. For ac current, multiple EPs appear for a certain gain-loss strength and mark the boundaries between the preserved PT-symmetry and the broken PT-symmetry phases. The number of islands of broken PT-symmetry phases and their extensions is tunable by the frequency and the strength of the spacer current. At EP and beyond, the induced and amplified magnetization oscillations are strong and self-sustained. In particular, these magnetization auto-oscillations in a broken PT-symmetry phase occur at low current densities and do not require further adjustments such as tilt angle between electric polarization and equilibrium magnetization direction in spin-torque oscillators, pointing to a new design of these oscillators and their utilization in computing and sensorics. It is also shown how the periodic gain-loss mechanism allows for the generation of high-frequency spin waves with low-frequency currents. For spatially periodic gain and loss acting on a magnonic crystal, magnon modes approaching each other at the Brillouin-zone boundaries are highly susceptible to PT symmetry, allowing for a wave-vector-resolved experimental realization at very low currents.

Safe surgical corridor for iliosacral screw placement in unstable pelvic fractures: a computed-tomography-guided validation study of the "triangulation method".

BACKGROUND: The percutaneous iliosacral screw technique represents a global standard fixation method for unstable fractures of the posterior pelvic ring. However, the inaccurate positioning of iliosacral screws is associated with a significant risk of severe intra-operative complications. Therefore, this study aimed to investigate the relationship between the skin entry point of the transverse iliosacral screw of the first sacral vertebral body and the anterior superior iliac spine and the greater trochanter of the femur using computed-tomography-guided validation. METHODS: Overall, 91 consecutive patients admitted to a tertiary referral center in China for posterior pelvic ring fixation via the "triangulation method" using computed-tomography-guided validation between January 1, 2020, and December 31, 2020, were included in this retrospective observational cohort study. Modeling and simulated iliosacral screw placement were performed using the Mimics software. The distance between the three points of interest was measured, and their relationship in a rectangular coordinate system was determined. Patients were categorized according to gender, body mass index, and femoral rotation angle to investigate the factors affecting the positional relationship between the three points. RESULTS: An equilateral triangular relationship was observed between the positioning points of the transverse iliosacral screw, anterior iliac spine, and greater trochanter. Additionally, 95% of the entry points were within a circle radius centered 12 mm at the apex of an equilateral triangle comprising the anterior superior iliac spine and the greater trochanter as the base. The entry point in the femoral external rotation was more dorsal than that in the internal femoral rotation. Furthermore, the entry point in females was more rostral than that in males, and the entry point in overweight patients was more dorsal than that in normal-weight patients. CONCLUSIONS: The skin entry point of the percutaneous iliosacral screw can be located by drawing an equilateral triangle from the anterior superior iliac spine and the greater trochanter as the base to the dorsum end of the patient's head. In summary, this retrospective cohort study validated the safety and efficacy of the "triangulation methods" for percutaneous fixation of unstable posterior pelvic ring injuries.

Review on the gentle hydrometallurgical treatment of WPCBs: Sustainable and selective gradient process for multiple valuable metals recovery.

The metal resource crisis and the inherent need for a low-carbon circular economy have driven the rapid development of e-waste recycling technology. High-value waste printed circuit boards (WPCBs) are an essential component of e-waste. However, WPCBs are considered hazardous to the ecosystem due to the presence of heavy metals and brominated organic polymers. Therefore, achieving the recycling of metals in WPCBs is not only a strategic requirement for building a green ecological civilization but also an essential guarantee for achieving a safe supply of mineral resources. This review systematically analyzes the hydrometallurgical technology of metals in WPCBs in recent years. Firstly, the different unit operations of pretreatment in the hydrometallurgical process, which contain disassembly, crushing, and pre-enrichment, were analyzed. Secondly, environmentally friendly hydrometallurgical leaching systems and high-value product regeneration technologies used in recent years to recover metals from WPCBs were evaluated. The leaching techniques, including cyanidation, halide, thiourea, and thiosulfate for precious metals, and inorganic acid, organic acid, and other leaching methods for base metals such as copper and nickel in WPCBs, were outlined, and the leaching performance and greenness of each leaching system were summarized and analyzed. Eventually, based on the advantages of each leaching system and the differences in chemical properties of metals in WPCBs, an integrated and multi-gradient green process for the recovery of WPCBs was proposed, which provides a sustainable pathway for the recovery of metals in WPCBs. This paper provides a reference for realizing the gradient hydrometallurgical recovery of metals from WPCBs to promote the recycling metal resources.

Eco-friendly approach for enhancing the floatability of non-metallic components in waste printed circuit boards: Adding gutter oil during dry grinding.

Waste printed circuit boards (WPCBs) are an attractive secondary resource that is challenging to dispose of due to its complexity. Reverse flotation is an effective method to remove non-metallic particles (NMPs) to obtain metals from WPCBs. Nevertheless, the removal of NMPs is usually inadequate in the present flotation practice. Thus, to provide a clean approach to improve the removal efficiency of NMPs, the method of adding gutter oil during dry grinding process was adopted to enhance the hydrophobic sites on the surface of NMPs to improve the floatability. The surface morphology of NMPs was analyzed by SEM, the results show that the rough morphology inhibited the adhesion of bubbles, while water occupied the cracks and pores, making it challenging for collector adsorption, which result in unstable particle-bubble adhesion. The results of FTIR indicate that both NMPs and gutter oil have -CH3, -CH2, -C = O, -C-O functional groups, which promotes the adsorption of gutter oil on the surface of NMPs. The contact angle (CA) results show that the adsorption of gutter oil on the particle surface is conducive to the formation of enhanced CA. Furthermore, the flotation enhancement effect was verified by flotation kinetic experiments. The accumulated floats yield of NMPs conditioned by gutter oil during grinding is increased from 67.05% (NMPs without conditioning) to 95.02%, and the resin recovery is increased by 31.10%. It is demonstrated that dry grinding with gutter oil can strengthen the floatability of NMPs, which provides a potential approach to increase the flotation efficiency of WPCBs.

UAV hyperspectral combined with LiDAR to estimate chlorophyll content at the stand and individual tree scales.

Chlorophyll is an important indicator of vegetation health status, accurate estimation of which is important for evaluating forest carbon sink. In this study, we estimated the chlorophyll content of coniferous forests, broad-leaved forests and mixed forest stands at stand and individual tree level by unmanned air vehicle (UAV) hyperspectral data combined with light detection and ranging (LiDAR) point clouds, which improved the non-destructive estimation accuracy of forest chlorophyll. We further comprehensively analyzed the spatial distribution of chlorophyll content at different scales. A total of 36 spectral characteristic variables related to chlorophyll content were screened by correlation analysis based on the fusion of UAV hyperspectral data and LiDAR point clouds combining with the empirical data from ground plots. We constructed multiple models for chlorophyll estimation by using statistical model, including multiple stepwise regression, BP neural network, BP neural network optimized by firefly algorithm, random forest and hybrid data-driven PROSPECT mechanism model. The optimal model was selected to estimate the chlorophyll content. The horizontal and vertical distribution of chlorophyll content at the stand level and individual tree level were analyzed. The results showed that the random forest model was superior to the models constructed by multiple stepwise regression, BP neural network and BP neural network optimized by firefly algorithm for chlorophyll estimation with R2 and RMSE of 0.59-0.64 and 3.79-5.83 µg·cm-2, respectively. The accuracy of the mechanism model was the highest, with R2 and RMSE of 0.97 and 3.40 µg·cm-2. The chlorophyll contents differed across stand types, with that in broad-leaved forest (25.25-31.60 µg·cm-2) being higher than mixed forest (13.52-23.93 µg·cm-2) and coniferous forest (6.40-13.71 µg·cm-2). There were significant differences in chlorophyll contents the in vertical direction among different stands. For individual tree of different species, the chlorophyll content inside the canopy was lower than that outside the canopy in the horizontal direction. In the vertical direction, there was no difference in chlorophyll content among different layers of Pinus sylvestris var. mongolica canopy. However, significant differences were observed among the upper, middle, and lower layers of Juglans mandshurica canopy. Using the fusion of hyperspectral image and LiDAR point cloud data, the mechanism model driven by hybrid data could effectively improve the accuracy and stability of chlorophyll content estimation at different scales.

Sequential treatment for diabetic foot ulcers in dialysis patients: A case report.

BACKGROUND: Diabetic foot ulcers (DFUs) are common in patients with diabetes, especially those undergoing hemodialysis. In severe cases, these ulcers can cause damage to the lower extremities and lead to amputation. Traditional treatments such as flap transposition and transfemoral amputation are not always applicable in all cases. Therefore, there is a need for alternative treatment methods. CASE SUMMARY: This report describes a 62-year-old female patient who was admitted to the hospital with plantar and heel ulcers on her left foot. The patient had a history of renal failure and was undergoing regular hemodialysis. Digital subtraction angiography showed extensive stenosis and occlusion in the left superficial femoral artery, left peroneal artery and left posterior tibial artery. Following evaluation by a multidisciplinary team, the patient was diagnosed with type 2 DFUs (TEXAS 4D). Traditional treatments were deemed unsuitable, and the patient was treated with endovascular surgery in the affected area, in addition to supportive medical treatment, local debridement, and sequential repair using split-thickness skin and tissue-engineered skin grafts combined with negative pressure treatment. After four months, the wound had completely healed, and the patient was able to walk with a walking aid. CONCLUSION: This study demonstrates a new treatment method for DFUs was successful, using angioplasty, skin grafts, and negative pressure.

Comment on "Ultrastructure reveals ancestral vertebrate pharyngeal skeleton in yunnanozoans".

Tian et al. (Reports, 8 July 2022, p. 218) claim that Cambrian yunnanozoan animals are stem vertebrates, based partly on their observation at the nanometer scale of microfibrillar tissue located in the branchial arches. They interpret this to represent cellular cartilage with an extracellular matrix of microfibrils. Instead, we argue that the 'microfibrils' are more likely modern organic contamination.

Protomelission is an early dasyclad alga and not a Cambrian bryozoan.

The animal phyla and their associated body plans originate from a singular burst of evolution occurring during the Cambrian period, over 500 million years ago1. The phylum Bryozoa, the colonial 'moss animals', have been the exception: convincing skeletons of this biomineralizing clade have been absent from Cambrian strata, in part because potential bryozoan fossils are difficult to distinguish from the modular skeletons of other animal and algal groups2,3. At present, the strongest candidate4 is the phosphatic microfossil Protomelission5. Here we describe exceptionally preserved non-mineralized anatomy in Protomelission-like macrofossils from the Xiaoshiba Lagerstätte6. Taken alongside the detailed skeletal construction and the potential taphonomic origin of 'zooid apertures', we consider that Protomelission is better interpreted as the earliest dasycladalean green alga-emphasizing the ecological role of benthic photosynthesizers in early Cambrian communities. Under this interpretation, Protomelission cannot inform the origins of the bryozoan body plan; despite a growing number of promising candidates7-9, there remain no unequivocal bryozoans of Cambrian age.

Treatment strategy on traumatic mid-lumbar spondyloptosis with concomitant multiple injuries: A case report and literature review.

Spondyloptosis in the clinic is rarely reported. We herein present a 47-year-old female, who suffered from a crush injury directly by a heavy cylindrical object from the lateral side. She was diagnosed to have traumatic L3 spondyloptosis with multiple traumas. Staged surgical procedures were conducted and a three-year follow-up was obtained. Eventually, normal spinal alignment was restored, and neurological deficits were gradually improved. At three years follow-up, the motor strength scores and function of the sphincters were incompletely improved. Previously published reports on traumatic lumbar spondyloptosis were reviewed and several critical points for management of this severe type of spinal injury were proposed. First, thoracolumbar and lumbosacral junction were mostly predilection sites. Second, numerous patients involving traumatic lumbar spondyloptosis were achieved to American Spinal Injury Association grade A. Third, lumbar spondyloptosis was commonly coupling with cauda equina injury. Finally, the outcomes were still with poorly prognosis and recovery of patients was correlation to spondyloptosis severity. Based on this case report and literatures review, we highlighted that the spinal alignment restoration relying on staged operations and following rehabilitation hereof are both important once facing with multiple traumas. Furthermore, we suggested to perform routine CT angiography during lumbar spondyloptosis to justify whether there are large vessel compression or injury.

Clinical characteristics, allergic response to autologous semen, and desensitization in patients with postorgasmic illness syndrome.

Introduction: Postorgasmic illness syndrome (POIS) is rare and includes a cluster of physical and cognitive symptoms that occur after ejaculation. The pathogenesis and effective treatments remain unclear. Aim: This study aimed to characterize the symptomatology of POIS, study the allergic response of autologous semen in patients and controls, and evaluate the effects of desensitization therapy. Methods: The clinical characteristics of 24 Chinese patients with POIS were analyzed. Skin prick tests, intracutaneous tests, and specific IgE detection were performed with autologous semen. Five patients were desensitized via subcutaneous injections of autologous semen. Outcomes: Evaluated outcomes included the clinical features of POIS; scores of the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and visual analog scale (VAS) of symptoms; skin reactions; desensitization with diluted autologous seminal fluid; and the IgE reactivity patterns of immunoblotting and enzyme-linked immunosorbent assay in vitro. Results: The most common symptom cluster was the general cluster, and the most prevalent symptoms were extreme fatigue and inattention. A total of 66.67% (14/21) of the patients had no symptoms or milder symptoms after nocturnal emission than after intercourse or masturbation. Of the patients, 87.5% (21/24) had psychiatric symptoms and 53.85% (7/13) had abnormal sex hormone levels. The SAS and SDS scores of the high and low VAS groups were significantly higher than those of the control group. Pearson analysis showed that the correlation coefficient between the SAS and VAS was 0.607 (P < .01) and that between the SDS and VAS was 0.490 (P < .05). The patients and healthy donors all had positive intracutaneous test results with their own semen, negative skin prick test results, and no IgE specific to autologous semen. Most patients (4/5) did not achieve ideal therapeutic effects with desensitization. Clinical Implications: Allergy is not the main pathogenesis of POIS, and desensitization with autologous semen is not effective for most patients. Strengths and Limitations: This project included the largest number of patients with POIS in China and assessed the allergic response to autologous semen and the effect of desensitization therapy. There is no objective method for evaluating the efficacy of desensitization with autologous semen. Conclusions: IgE-mediated semen allergy is not the main pathogenesis of POIS, and there is a positive chance that POIS is related to psychological factors. Most patients do not respond to desensitization with autologous semen, and POIS treatment should be individualized, especially in cases with uncertain causes.

Treatment strategy on traumatic mid-lumbar spondyloptosis with concomitant multiple injuries: A case report and literature review / 中华创伤杂志(英文版)

Spondyloptosis in the clinic is rarely reported. We herein present a 47-year-old female, who suffered from a crush injury directly by a heavy cylindrical object from the lateral side. She was diagnosed to have traumatic L3 spondyloptosis with multiple traumas. Staged surgical procedures were conducted and a three-year follow-up was obtained. Eventually, normal spinal alignment was restored, and neurological deficits were gradually improved. At three years follow-up, the motor strength scores and function of the sphincters were incompletely improved. Previously published reports on traumatic lumbar spondyloptosis were reviewed and several critical points for management of this severe type of spinal injury were proposed. First, thoracolumbar and lumbosacral junction were mostly predilection sites. Second, numerous patients involving traumatic lumbar spondyloptosis were achieved to American Spinal Injury Association grade A. Third, lumbar spondyloptosis was commonly coupling with cauda equina injury. Finally, the outcomes were still with poorly prognosis and recovery of patients was correlation to spondyloptosis severity. Based on this case report and literatures review, we highlighted that the spinal alignment restoration relying on staged operations and following rehabilitation hereof are both important once facing with multiple traumas. Furthermore, we suggested to perform routine CT angiography during lumbar spondyloptosis to justify whether there are large vessel compression or injury.

The risk surveillance of schistosomiasis in Yunnan, 2021 / 中国热带医学

@#Abstract: Objective　To evaluate the potential transmission risk of schistosomiasis in Yunnan Province, and to provide strategic basis for the prevention and control. Methods　Based on the prevalence of schistosomiasis, the social and environmental factors that may lead to the epidemic, 1-3 villages from 3 provincial-level and 15 county-level counties (cities and districts) were selected as the evaluated villages in 2021. The risk of schistosomiasis spread was analyzed comprehensively by consulting, reviewing and collecting routine surveillance data of schistosomiasis in the villages, combined with snail and wild feces survey. The risk level was evaluated for the positive snails, positive wild feces, resident infection, average density of live snails and snail frame occurrence rate. Results　Totally 7 snail counties schistosomiasis transmission was blocked of 18 epidemic counties and the rest were eliminated counties. A total of 152 447 snail frames were investigated and 3 043 frames with snails, 15 895 snails were captured and included 15 727 live snails in the 32 evaluated villages. The total area of snail was 58.87 hm2 and the area of reoccurrence was 34.19 hm2 with snail frame occurrence rate of 2.00% and average density of live snails 0.103 2/0.11 m2, and no positive snails were found by loop-mediated isothermal amplification (LAMP) assay. A total of 1 374 wild feces were collected in 27 evaluated villages of 14 epidemic counties, mainly from cattle, dogs, sheep, equine animals, pigs and so on, all of which were negative. According to the risk assessment of epidemic spread, Yongle Village and Yongsheng Village in Eryuan County, Zhiming Village in Chuxiong City were Ⅱ risk, and the rest were Ⅲ risk. Conclusions　Although the risk of transmission is low in Yunnan Province, the risk of transmission and spread still exists. It is necessary to strengthen the risk monitoring, control of snail and effective management of livestock to prevent the rebound of the epidemic.

The acute-to-chronic glycemic ratio correlates with the severity of illness at admission in patients with diabetes experiencing acute ischemic stroke.

Acute hyperglycemia is a powerful indicator of the severity of acute ischemic stroke (AIS); however, the relationship between these two factors is not very clear in patients with diabetes. We aimed to retrospectively evaluate data from 335 consecutive patients who experienced AIS from November 2015 to November 2016 to investigate whether a comprehensive assessment of blood glucose levels is a more valuable indicator of the severity of AIS or the presence of acute hyperglycemia in patients with diabetes. We collected demographic data, clinical manifestation information, clinical scores, and laboratory data [including fasting blood glucose and glycated hemoglobin (HbA1c) levels]. We estimated prehospital mean blood glucose concentrations using the following formula [1.59 * HbA1c (%) - 2.59] to calculate the "Acute-to-Chronic Glycemic Ratio" (AC ratio). The AC ratio differed significantly among patients grouped according to the National Institutes of Health Stroke Scale/Score (NIHSS) at admission (admission NIHSS) (p = 0.006). Univariate regression analysis revealed a correlation between the AC ratio and admission NIHSS [standardized ß-coefficient (Std. B) = 0.164, p = 0.004]. The adjusted linear regression analysis revealed a correlation between both HbA1c (Std. B = 0.368, p = 0.038) and the AC ratio (Std. B = 0.262, p = 0.022) and admission NIHSS. The AC ratio (Std. B = 0.161, p = 0.012) was related to admission NIHSS in the stepwise variable selection. For an admission NIHHS > 4, the AC ratio (Std. B = 0.186, p = 0.047) was related to admission NIHSS in the stepwise variable selection. The AC ratio (Std. B = 1.163, p = 0.006 and Std. B = 0.565, p = 0.021, respectively) were related to admission NIHSS in both large-artery atherosclerosis (LAA) and small-vessel occlusion (SVO) subgroups. Thus, the AC ratio is related to admission NIHSS in patients with diabetes who experienced AIS and may be a better indicator of severity than acute blood glucose levels.

Bridging nanoplatform and vaccine delivery, a landscape of strategy to enhance nasal immunity.

Vaccination is an urgently needed and effective option to address epidemic, cancers, allergies, and other diseases. Nasal administration of vaccines offers many benefits over needle-based injection including high compliance and less risk of infection. Inactivated or attenuated vaccines as convention vaccine present potential risks of pathogenic virulence reversal, the focus of nasal vaccine development has shifted to the use of next-generation (subunit and nucleic acid) vaccines. However, subunit and nucleic acid vaccine intranasally have numerous challenges in development and utilization due to mucociliary clearance, mucosal epithelial tight junction, and enzyme/pH degradation. Nanoplatforms as ideal delivery systems, with the ability to enhance the retention, penetration, and uptake of nasal mucosa, shows great potential in improving immunogenic efficacy of nasal vaccine. This review provides an overview of delivery strategies for overcoming nasal barrier, including mucosal adhesion, mucus penetration, targeting of antigen presenting cells (APCs), enhancement of paracellular transportation. We discuss methods of enhancing antigen immunogenicity by nanoplatforms as immune-modulators or multi-antigen co-delivery. Meanwhile, we describe the application status and development prospect of nanoplatforms for nasal vaccine administration. Development of nanoplatforms for vaccine delivery via nasal route will facilitate large-scale and faster global vaccination, helping to address the threat of epidemics.

Reshaping hypoxia and silencing CD73 via biomimetic gelatin nanotherapeutics to boost immunotherapy.

The ubiquitous hypoxic microenvironment at the tumor site helps to regulate hypoxic inducible factor (HIF-1α), up-regulate downstream CD73-adenosine (CD73-ADO) pathways, and further result in effector T cell function exhaustion, which is regarded as a crucial adverse factor in the poor clinical efficacy of immune checkpoint blockade therapy (ICB). How to reshape hypoxic microenvironment and silence CD73 remains a huge challenge to improve ICB therapeutic outcomes. In this study, cancer cell membrane-camouflaged gelatin nanoparticles (CSG@B16F10) were designed to co-deliver oxygen-generating agent catalase (CAT) and CD73siRNA, thus enhancing tumor oxygenation and alleviating CD73-ADO pathway-mediated T cell immunosuppression. The fabricated biomimetic nanoparticles could efficiently achieve immune evading and homologous targeting by virtue of the retention of cancer cell membrane protein. Matrix metalloproteinases (MMP)-responsive gelatin nanoparticles were gradually disintegrated to accelerate the release of payloads. Rapidly released CAT was found to relieve tumor hypoxia by generating endogenous oxygen, while CD73siRNA effectively silenced target gene, synergically inhibiting CD73 protein expression and facilitating T-cell-specific immunity. Upon introduction of CSG@B16F10 in melanoma-bearing mice, PD-L1 checkpoint blockade achieved optimal tumor suppression (∼83%). The enhanced immune efficacy was mainly manifested by enhanced cytotoxic T cell (CTL), reduced regulatory T cells (Tregs), and increased anti-tumor cytokine secretion. This work presents a new paradigm for the ideal design of biomimetic nanoplatforms and the synergistic treatment of hypoxia alleviation and CD73 silence, greatly promising for enhancing clinical immune potency of PD-1/PD-L1 immune checkpoint blockade.

Oncological Safety of Diagnostic Hysteroscopy for Apparent Early-Stage Type II Endometrial Cancer: A Multicenter Retrospective Cohort Study.

Objective: To study the oncological safety of diagnostic hysteroscopy for women with apparent early-stage type II endometrial cancer. Patients and Methods: A total of 429 women with presumed early-stage type II endometrial cancer were included. The 5-year disease-free survival (DFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method and the log-rank test among patients diagnosed by Dilation & Curettage (D&C) or diagnostic hysteroscopy. The Cox proportional hazards regression model was employed to adjust for potential confounding factors. Results: 160 cases underwent D&C and 269 cases were diagnosed by diagnostic hysteroscopy. The 5-year DFS rate was 72.17% in the diagnostic hysteroscopy group and 76.16% in the D&C group, diagnostic hysteroscopy was not associated with deteriorated 5-year DFS rate (HR 1.25, 95% CI 0.84-1.86, P=0.281). The 5-year OS rate was 67.23% in the diagnostic hysteroscopy group and 70.71% in the D&C group, diagnostic hysteroscopy did not increase the risk of all-cause death (HR 1.11, 95% CI 0.78-1.57, P=0.573). Multivariable analysis showed that the method of endometrial sampling was not independently associated with DFS (aHR 1.38, 95% CI 0.92-2.07, P=0.122) and OS (aHR 1.23, 95% CI 0.85-1.77, P=0.272). Conclusion: For apparent early-stage type II endometrial cancer, endometrial sampling by diagnostic hysteroscopy was as safe as D&C.