Visible-light induced selenocyclization of 2-ethynylanilines under ambient conditions: simple FeBr3 as a dual-functional catalyst.

We report herein a visible-light induced, Fe-catalyzed selenocyclization of 2-ethynylanilines with diselenides under ambient conditions, employing ethyl acetate as a benign solvent with no stoichiometric additive required. The simple iron salt FeBr3 serves as both a photo-induced LMCT (Ligand-to-Metal Charge Transfer) catalyst and a Lewis acid catalyst to promote the desired transformation in a sustainable manner, enabling the facile synthesis of diverse 3-selenylindoles with extended substitution patterns. Moreover, gram-scale reactions and late-stage functionalization of bioactive molecules further highlight the synthetic practicality of this method.

SMC2 knockdown inhibits malignant progression of lung adenocarcinoma by upregulating BTG2 expression.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer worldwide. Structural maintenance of chromosomes 2 (SMC2) serves as a predictor of poor prognosis across various cancer types. This study aims to explore the role and underlying mechanisms of SMC2 in LUAD progression. The expression of SMC2 in LUAD tissues and its correlation with prognosis were analyzed by public databases. Knockdown of SMC2 was performed to assess the proliferation, migration and invasion ability of LUAD cells. Bulk RNA sequencing analysis identified enriched cellular pathways and remarkable upregulation of BTG anti-proliferation factor 2 (BTG2) expression after SMC2 knockdown in LUAD cells. Then, BTG2 was silenced to assess the malignant behavior of LUAD cells. Subcutaneous transplantation and intracranial tumor models of LUAD cells in BALB/c nude mice were established to assess the antineoplastic effect of SMC2 knockdown in vivo. Additionally, a lung metastasis model was created to evaluate the pro-metastatic effect of SMC2. Our findings indicated that SMC2 was upregulated in LUAD tissues and cell lines, with higher expression correlating with poor prognosis. SMC2 silencing suppressed the proliferation, migration and invasion ability of LUAD cells by upregulating BTG2 expression via p53 and inactivating ERK and AKT pathways. BTG2 silencing reversed the effects of SMC2 downregulation on malignant behaviors of LUAD cells and restored the phosphorylated ERK and AKT levels. Furthermore, SMC2 knockdown effectively prevented the formation of subcutaneous, intracranial and metastatic tumor in vivo, and upregulation of BTG2 expression after SMC2 knockdown was confirmed in tumor models. This study revealed that SMC2 knockdown restrained the malignant progression of LUAD through upregulation of BTG2 expression and inactivation of ERK and AKT pathways, and SMC2 could be a potential therapeutic target for LUAD treatment.

A next-generation STING agonist MSA-2: From mechanism to application.

The stimulator of interferon genes (STING) connects the innate and adaptive immune system and plays a significant role in antitumor immunity. Over the past decades, endogenous and CDN-derived STING agonists have been a hot topic in the research of cancer immunotherapies. However, these STING agonists are either in infancy with limited biological effects or have failed in clinical trials. In 2020, a non-nucleotide STING agonist MSA-2 was identified, which exhibited satisfactory antitumor effects in animal studies and is amenable to oral administration. Due to its distinctive binding mode and enhanced bioavailability, there have been accumulating interests and an array of studies on MSA-2 and its derivatives, spanning its structure-activity relationship, delivery systems, applications in combination therapies, etc. Here, we provide a comprehensive review of MSA-2 and interventional strategies based on this family of STING agonists to help more researchers extend the investigation on MSA-2 in the future.

Spleen-targeted delivery systems and strategies for spleen-related diseases.

The spleen, body's largest secondary lymphoid organ, is also a vital hematopoietic and immunological organ. It is regarded as one of the most significant organs in humans. As more researchers recognize the functions of the spleen, clinical methods for treating splenic diseases and spleen-targeted drug delivery systems to improve the efficacy of spleen-related therapies have gradually developed. Many modification strategies (size, charge, ligand, protein corona) and hitchhiking strategies (erythrocytes, neutrophils) of nanoparticles (NPs) have shown a significant increase in spleen targeting efficiency. However, most of the targeted drug therapy strategies for the spleen are to enhance or inhibit the immune function of the spleen to achieve therapeutic effects, and there are few studies on spleen-related diseases. In this review, we not only provide a detailed summary of the design rules for spleen-targeted drug delivery systems in recent years, but also introduce common spleen diseases (splenic tumors, splenic injuries, and splenomegaly) with the hopes of generating more ideas for future spleen research.

Enhancing Fresh-Cut Apple Preservation: Impact of Slightly Acidic Electrolyzed Water and Chitosan-Apple Essence Microencapsulation Coating on Browning and Flavor.

Fresh-cut apple preservation is a critical concern in the food industry due to the rapid deterioration of texture, color, and flavor. While our previous study introduced apple essence microencapsulation (AEM) to enhance flavor during storage, its impact on overall storage quality was minimal. Thus, this study explores the application of two preservation techniques, namely, slightly acidic electrolyzed water (SAEW) and chitosan-apple essence microencapsulation (CH-AEM) coating, to enhance the quality of fresh-cut apples. Our findings reveal that SAEW treatment significantly reduces the browning index (from 65.38 to 57.36) and respiratory rate (from 5.10% to 4.30% of CO2), and maintains a desirable aroma profile compared to uncoated treatment during 10 days of storage. Additionally, the CH-AEM coating acts as a protective barrier, further preserving the sensory characteristics of fresh-cut apples. Notably, the SAEW-CH-AEM group exhibits superior performance in firmness (8.14 N), respiratory rate (3.37% of CO2), ion leakage (34.86%), and juice yield (47.52%) after 10 days. Our research highlights the synergistic effect of combining these preservation strategies, providing a promising approach for extending the shelf life of fresh-cut apples while maintaining their visual appeal and aromatic quality. These results offer valuable insights for the fresh-cut produce industry, contributing to improved apple product preservation and consumer satisfaction.

Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios (OR) were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 mo). Publication bias was assessed using Begg's test, and Egger's test. RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery (total thyroidectomy (TT) vs. lobectomy), surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

Background: Local infiltration analgesia (LIA) provides postoperative analgesia for total knee arthroplasty (TKA). The purpose of this study was to evaluate the analgesic effect of a cocktail of ropivacaine, morphine, and Diprospan for TKA. Methods: A total of 100 patients from September 2018 to February 2019 were randomized into 2 groups. Group A (control group, 50 patients) received LIA of ropivacaine alone (80 ml, 0.25% ropivacaine). Group B (LIA group, 50 patients) received an LIA cocktail of ropivacaine, morphine, and Diprospan (80 ml, 0.25% ropivacaine, 0.125 mg/ml morphine, and 62.5 µg/ml compound betamethasone). The primary outcomes were the levels of inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), pain visual analog scale (VAS) scores, opioid consumption, range of motion (ROM), functional tests, and sleeping quality. The secondary outcomes were adverse events, satisfaction rates, HSS scores, and SF-12 scores. The longest follow-up was 2 years. Results: The two groups showed no differences in terms of characteristics (P > 0.05). Group B had lower resting VAS pain scores (1.54 ± 0.60, 95% CI = 1.37 to 1.70 vs. 2.00 ± 0.63, 95% CI = 2.05 to 2.34) and active VAS pain scores (2.64 ± 0.62, 95% CI = 2.46 to 2.81 vs. 3.16 ± 0.75, 95% CI = 2.95 to 3.36) within 48 h postoperatively than Group A (P < 0.001), while none of the pain differences exceeded the minimal clinically important difference (MCID). Group B had significantly lower CRP levels (59.49 ± 13.01, 95% CI = 55.88 to 63.09 vs. 65.95 ± 14.41, 95% CI = 61.95 to 69.94) and IL-6 levels (44.11 ± 13.67, 95% CI = 40.32 to 47.89 vs. 60.72 ± 15.49, 95% CI = 56.42 to 65.01), lower opioid consumption (7.60 ± 11.10, 95% CI = 4.52 to 10.67 vs. 13.80 ± 14.68, 95% CI = 9.73 to 17.86), better ROM (110.20 ± 10.46, 95% CI = 107.30 to 113.09 vs. 105.30 ± 10.02, 95% CI = 102.52 to 108.07), better sleep quality (3.40 ± 1.03, 95% CI = 3.11 to 3.68 vs. 4.20 ± 1.06, 95% CI = 3.90 to 4.49), and higher satisfaction rates than Group A within 48 h postoperatively (P < 0.05). Adverse events, HSS scores, and SF-12 scores were not significantly different within 2 years postoperatively. Conclusions: A cocktail of ropivacaine, morphine, and Diprospan prolongs the analgesic effect up to 48 h postoperatively. Although the small statistical benefit may not result in MCID, the LIA cocktail still reduces opioid consumption, results in better sleeping quality and faster rehabilitation, and does not increase adverse events. Therefore, cocktails of ropivacaine, morphine, and Diprospan have good application value for pain control in TKA. This trial is registered with ChiCTR1800018372.

VOC and IVOC emission features and inventory of motorcycles in China.

How did the motorcycle emissions evolve during the economic development in China? To address data gaps, this study firstly measured the volatile organic compound (VOC) and intermediate-volatility organic compound (IVOC) emissions from motorcycles. The results confirmed that the emission control of motorcycles, especially small-displacement motorcycles, significantly lagged behind other gasoline-powered vehicles. For the China IV motorcycles, the average VOC and IVOC emission factors (EFs) were 2.74 and 7.78 times higher than the China V-VI light-duty gasoline vehicles, respectively. The notable high IVOC emissions were attributed to a dual influence from gasoline and lubricating oil. Furthermore, based on the complete EF dataset and economy-related activity data, a county-level emission inventory was developed in China. Motorcycle VOC and IVOC emissions changed from 2536.48 Gg and 197.19 Gg in 2006 to 594.21 Gg and 12.66 Gg in 2020, respectively. The absence of motorcycle IVOC emissions in the existed vehicular inventories led to an underestimation of up to 20%. Across the 15 years, the motorcycle VOC and IVOC emission hotspots were concentrated in the undeveloped regions, with the rural emissions reaching 5.81-10.14 times those of the urban emissions. This study provides the first-hand and close-to-realistic data to support motorcycle emission management and accurate air quality simulations.

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease.

Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aß accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.

Biomechanical Study of Porcine Osteoporotic Vertebral Compression Fracture Model Strengthened by Trajectory-Adjustable Bone Cement Filling Device.

OBJECTIVE: To establish a porcine osteoporotic vertebral compression fracture model and compare the impact of unilateral vertebroplasty using trajectory-adjustable bone cement filling device to traditional surgical tools on vertebral biomechanics. METHODS: Twenty-four fresh adult porcine vertebrae were used to establish an osteoporotic vertebral compression fracture model. The specimens were divided into 4 groups (A, B, C, and D), each consisting of 6 vertebrae. Group A served as the control group without vertebral augmentation (percutaneous vertebroplasty [PVP]). Patients in Group B underwent unilateral PVP using conventional surgical tools, while patients in Group C underwent bilateral PVP using the same tools. In Group D, patients underwent unilateral PVP with a trajectory-adjustable bone cement filling device. Postoperative X-ray examinations were performed to assess cement distribution and leakage. The compressive stiffness and strength of each spinal unit were evaluated using an electronic mechanical testing machine. RESULTS: In Groups B, C, and D, the percentages of total cement distribution area were 32.83 ± 3.64%, 45.73 ± 2.27%, and 47.43 ± 3.51%, respectively. The values were significantly greater in Groups C and D than in Group B (P < 0.05), but there was no significant difference between Groups C and D (P > 0.05). The stiffness after vertebral augmentation in Groups B, C, and D was 1.04 ± 0.23 kN/mm, 1.11 ± 0.16 KN/mm, and 1.15 ± 0.13 KN/mm, respectively, which were significantly greater than that in Group A (0.46 ± 0.06 kN/mm; P < 0.05). The ultimate compressive strengths in Groups B, C, and D were 2.53 ± 0.21 MPa, 4.09 ± 0.30 MPa, and 3.99 ± 0.29 MPa, respectively, all surpassing Group A's strength of 1.41 ± 0.31 MPa. Additionally, both Groups C and D demonstrated significantly greater ultimate compressive strengths than Group B did (P < 0.05). CONCLUSIONS: A trajectory-adjustable bone cement filling device was proven to be an effective approach for unilateral vertebroplasty, restoring the biomechanical properties of fractured vertebrae. Compared to traditional surgical tools, this approach is superior to unilateral puncture and yields outcomes comparable to those of bilateral puncture. Additionally, the device ensures a centrally symmetrical distribution pattern of bone cement, leading to improved morphology.

Development of a low-cost and accurate carrier screening method for spinal muscular atrophy in developing countries.

Heterozygous carriers of the survival of motor neuron 1 (SMN1) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods. Herein, we aimed to develop a low-cost, accessible, and accurate carrier screening method based on duplex droplet digital PCR (ddPCR), to cover a wider population in developing countries, including China. The receiver operating characteristic curve was used to determine the cut-off value of SMN1 copy numbers. Performance validation was conducted for linearity, precision, and accuracy. In total, 482 cases were considered to validate the concordance between the developed ddPCR assay and multiplex ligation-dependent probe amplification. Linear correlations were excellent between the expected concentration of the reference gene and the observed values (R2 > 0.99). Both the intra- and inter-assay precision of our ddPCR assays were less than 6.0%. The multiplex ligation-dependent probe amplification and ddPCR results were consistent in 480 of the 482 cases (99.6%). Two cases with multiplex ligation-dependent probe amplification, suggestive of two copies of SMN1 exon 7, were classified into three copies by ddPCR analysis. The overall correct classification of the samples included in our ddPCR assay was 100%. This study demonstrates that an appropriate cut-off value is an important prerequisite for establishing a semi-quantitative method to determine the SMN1 copy numbers. Compared to conventional methods, our ddPCR assay is low-cost, highly accurate, and has full potential for application in population spinal muscular atrophy carriers screening.

A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice.

Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.

Advancing shipping NOx pollution estimation through a satellite-based approach.

Estimating shipping nitrogen oxides (NOx) emissions and their associated ambient NO2 impacts is a complex and time-consuming task. In this study, a satellite-based ship pollution estimation model (SAT-SHIP) is developed to estimate regional shipping NOx emissions and their contribution to ambient NO2 concentrations in China. Unlike the traditional bottom-up approach, SAT-SHIP employs satellite observations with varying wind patterns to improve the top-down emission inversion methods for individual sectors amidst irregular emission plume signals. Through SAT-SHIP, shipping NOx emissions for 17 ports in China are estimated. The results show that SAT-SHIP performed comparably with the bottom-up approach, with an R2 value of 0.8. Additionally, SAT-SHIP reveals that the shipping sector in port areas contributes ∼21 and 11% to NO2 concentrations in the Yangtze River Delta and Pearl River Delta areas of China, respectively, which is consistent with the results from chemical transportation model simulations. This approach has practical implications for policymakers seeking to identify pollution sources and develop effective strategies to mitigate air pollution.

The Synergistic Effect of Additives for Formamidinium-Based Inverted Dion-Jacobson 2D Perovskite Solar Cells with Enhanced Photovoltaic Performance.

Two-dimensional (2D) perovskite solar cells (PSCs) have attracted rapid growing attention due to their excellent environmental and operational stability. As an important type of 2D perovskite, Dion-Jacobson (DJ) 2D perovskites exhibit better structural integrity and more stable optoelectronic properties than those of Ruddlesden-Popper (RP) ones because of the elimination of weak van der Waals interactions. Random phase distribution, phase impurity, and weak crystallinity, however, can lead to severe nonradiative recombination losses in 2D perovskites and inferior device stability. Herein, formamidinium chloride (FACl) and lead chloride (PbCl2) are selected as additives to fabricate efficient and stable DJ 2D PSCs. The synergistic effect of additives could efficiently induce crystallization and suppress the low-n phase perovskites. The obtained 2D perovskites exhibit extended charge lifetime and enhanced charge transfer. The corresponding PSC device delivers an efficiency of 16.63% with a significantly improved open-circuit voltage (VOC) of 1.18 V and a fill factor (FF) of 81.65% than the control one. This PCE ranks the highest for inverted FA-based 2D DJ PSCs. Moreover, this device has exhibited exceptional long-term stability, which retains more than 95% of the initial efficiencies at about 50% relative humidity for 600 h.

Ultra-high-resolution mapping of ambient fine particulate matter to estimate human exposure in Beijing.

With the decreasing regional-transported levels, the health risk assessment derived from fine particulate matter (PM2.5) has become insufficient to reflect the contribution of local source heterogeneity to the exposure differences. Here, we combined the both ultra-high-resolution PM2.5 concentration with population distribution to provide the personal daily PM2.5 internal dose considering the indoor/outdoor exposure difference. A 30-m PM2.5 assimilating method was developed fusing multiple auxiliary predictors, achieving higher accuracy (R2 = 0.78-0.82) than the chemical transport model outputs without any post-simulation data-oriented enhancement (R2 = 0.31-0.64). Weekly difference was identified from hourly mobile signaling data in 30-m resolution population distribution. The population-weighted ambient PM2.5 concentrations range among districts but fail to reflect exposure differences. Derived from the indoor/outdoor ratio, the average indoor PM2.5 concentration was 26.5 µg/m3. The internal dose based on the assimilated indoor/outdoor PM2.5 concentration shows high exposure diversity among sub-groups, and the attributed mortality increased by 24.0% than the coarser unassimilated model.

Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution.

Macrophages are central to the pathogenesis of kidney disease and serve as an effective therapeutic target for kidney injury and fibrosis. Among them, M2-type macrophages have double-edged effects regarding anti-inflammatory effects and tissue repair. Depending on the polarization of the M2 subtypes (M2a or M2c) in the diseased microenvironment, they can either mediate normal tissue repair or drive tissue fibrosis. In renal fibrosis, M2a promotes disease progression through macrophage-to-myofibroblast transition (MMT) cells, while M2c possesses potent anti-inflammatory functions and promotes tissue repair, and is inhibited. The mechanisms underlying this differentiation are complex and are currently not well understood. Therefore, in this study, we first confirmed that M2a-derived MMT cells are responsible for the development of renal fibrosis and demonstrated that the intensity of TGF-ß signaling is a major factor determining the differential polarization of M2a and M2c. Under excessive TGF-ß stimulation, M2a undergoes a process known as MMT cells, whereas moderate TGF-ß stimulation favors the polarization of M2c phenotype macrophages. Based on these findings, we employed targeted nanotechnology to codeliver endoplasmic reticulum stress (ERS) inhibitor (Ceapin 7, Cea or C) and conventional glucocorticoids (Dexamethasone, Dex or D), precisely modulating the ATF6/TGF-ß/Smad3 signaling axis within macrophages. This approach calibrated the level of TGF-ß stimulation on macrophages, promoting their polarization toward the M2c phenotype and suppressing excessive MMT polarization. The study indicates that the combination of ERS inhibitor and a first-line anti-inflammatory drug holds promise as an effective therapeutic approach for renal fibrosis resolution.

Electrochemical selenocyclization of 2-ethynylanilines with diselenides: facile and efficient access to 3-selenylindoles.

An efficient electrochemical selenocyclization strategy for the synthesis of 3-selenylindoles from 2-ethynylanilines and diselenides has been developed in simple tube- or beaker-type undivided cells under ambient conditions. Notably, these sustainable transformations are completed within a short time with low equivalents of charges, diselenides and electrolytes, exhibiting a broad substrate scope with excellent functional group compatibility. Moreover, a gram-scale electrosynthesis and late-stage functionalization of complex molecules further demonstrate the practical synthetic potential of this facile electrochemical system.

Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity.

Despite significant progress in vaccine development, especially in the fight against viral infections, many unexplored areas remain including innovative adjuvants, diversification of vaccine formulations, and research into the coordination of humoral and cellular immune mechanisms induced by vaccines. Effective coordination of humoral and cellular immunity is crucial in vaccine design. In this study, we used the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or ovalbumin (OVA) as antigen models and CpG DNA (an activator of toll-like receptor 9, TLR9) as an adjuvant to prepare a multitargeted liposome (LIPO) vaccine. Once equipped with the ability to target lymph nodes (LN) and the endoplasmic reticulum (ER), the LIPO vaccine significantly enhances the cross-presentation ability of antigen-presenting cells (APCs) for exogenous antigens through the ER-associated protein degradation (ERSD) mechanism. Additionally, the vaccine could fine-tune the efficiency of ER-targeted antigen delivery, actively regulating the presentation of exogenous antigen proteins via the major histocompatibility complex (MHC-I) or MHC-II pathways. Immune data from in vivo mouse experiments indicated that the LIPO vaccine effectively stimulated both humoral and cellular immune responses. Furthermore, it triggers immune protection by establishing a robust and persistent germinal center. Moreover, the multifunctionality of this LIPO vaccine extends to the fields of cancer, viruses, and bacteria, providing insights for skilled vaccine design and improvement.

Solvent exchange-motivated and tunable in situ forming implants sustaining triamcinolone acetonide release for arthritis treatment.

Arthritis is a syndrome characterized by inflammation in the joints. Triamcinolone acetonide (TA) was used as an anti-inflammatory agent in the treatment of this disease. However, there are limitations to its clinical application, including rapid clearance from the joint cavity, potential joint damage from multiple injections, and adverse joint events. To address these drawbacks, we developed a tunable in situ forming implant loaded with TA. This injectable polymer solution utilized poly (lactic-co-glycolic acid) (PLGA) as an extended-release material. When injected into the joints, the solution solidifies into implants through a solvent exchange in the aqueous environment. The implants demonstrated robust retention at the injection site and released TA over several weeks even months through diffusion and erosion. By adding different proportions of low water-miscible plasticizers, the release period of the drug could be precisely adjusted. The plasticizers-optimized implants exhibited a tough texture, enhancing the therapeutic efficiency and drug safety in vivo. In arthritic model studies, the tunable TA-loaded implants significantly reduced swelling, pain, and motor discoordination, and also showed suppression of arthritis progression to some extent. These findings suggested that TA-loaded ISFI holds promise for managing inflammatory disorders in individuals with arthritis.