Harnessing External Irradiation for Precise Activation of Metal-Based Agents in Cancer Therapy.

Cancer is a significant global health issue. Platinum-based chemotherapy drugs, including cisplatin, are crucial in clinical anti-cancer treatment. However, these drugs have limitations such as drug resistance, non-specific distribution, and irreversible toxic and side effects. In recent years, the development of metal-based agents has led to the discovery of other anti-cancer effects beyond chemotherapy. Precise spatiotemporal controlled external irradiation can activate metal-based agents at specific sites and play a different role from traditional chemotherapy. These strategies can not only enhance the anti-cancer efficiency, but also show fewer side effects and non-cross-drug resistance, which are ideal approaches to solve the problems caused by traditional platinum-based chemotherapy drugs. In this review, we focus onvarious metal-based agent-mediated cancer therapies that are activated by three types of external irradiation: near-infrared (NIR) light, ultrasound (US), and X-ray, and give some prospects. We hope that this review will promote the generation of new kinds of metal-based anti-cancer agents.

The Contribution of Meckel's Cartilage-Derived Type II Collagen-Positive Cells to the Jawbone Development and Repair.

Jawbones and long bones, despite their shared skeletal lineage, frequently exhibit distinct origins and developmental pathways. Identifying specific progenitor subsets for mandibular osteogenesis remains challenging. Type II collagen is conventionally associated with cartilaginous structures, yet our investigation has identified the presence of type II collagen positive (Col2+) cells within the jawbone development and regeneration. The role of Col2+ cells in jawbone morphogenesis and repair has remained enigmatic. In this study, we analyze single-cell RNA sequencing data from mice jawbone at embryonic day 10.5. Through fate-mapping experiments, we have elucidated that Col2+ cells and their progeny are instrumental in mandibular osteogenesis across both fetal and postnatal stages. Furthermore, lineage tracing with a tamoxifen-inducible CreER system has established the pivotal role of Col2+ cells, marked by Col2-CreER and originating from the primordial Meckel's cartilage, in jawbone formation. Moreover, our research explored models simulating jawbone defects and tooth extraction, which underscored the osteogenic differentiation capabilities of postnatal Col2+ cells during repair. This finding not only highlights the regenerative potential of Col2+ cells but also suggests their versatility in contributing to skeletal healing and regeneration. In conclusion, our findings position Col2+ cells as essential in orchestrating osteogenesis throughout the continuum of mandibular development and repair.

Parent-Child Relationship Buffers the Impact of Maternal Psychological Control on Aggression in Temperamentally Surgent Children.

Children's temperamental surgency is associated with later child behavioral problems. However, the underlying mechanisms linking child surgency and child aggression, such as negative parental control, are relatively understudied. Moreover, the potential protective effect of a close parent-child relationship on these associations remains untested, particularly among non-White families. Participants included 259 Chinese American preschoolers (Mage = 4.5 years, SD = 0.9 years, 50% girls) and their mothers (Mage = 37.9 years, SD = 4.7 years), the present study examined the moderating effects of parent-child relationship quality on the association between mother-rated child surgency and teacher-rated child aggression as mediated by maternal psychological control. Overall, results showed that child surgency was linked positively to maternal psychological control, which, in turn led to higher levels of child aggression six months later, but only when the parent-child relationship quality was less optimal. These findings indicate that psychological control is one underlying mechanism linking child temperament and child maladjustment, and that parent-child relationship quality is an important protective factor. Findings also expand an existing theoretical framework by explicating how these variables are applicable to an Asian American population, suggesting the critical buffering role that parent-child relationship quality plays. The study findings inform efforts to mitigate the potential negative effect of psychological control in reducing childhood aggression.

Mobile-enhanced Family Integrated Care for preterm infants: A qualitative study of parents' views.

Objective: The Family Integrated Care (FICare) model improves outcomes for preterm infants and parents compared with family-centered care (FCC). FICare with mobile technology (mFICare) may improve uptake and impact. Research on FICare in the United States (US) is scarce and little is known about parents' experience. Methods: We conducted qualitative interviews with nine parents, exploring their NICU experiences, participation in and perceptions of the mFICare program. A directed content analysis approach was used, and common themes were derived from the data. Results: Overall, parents had positive NICU experiences and found mFICare helpful in meeting three common parenting priorities: actively caring for their infant, learning how to care for their infant, and learning about the clinical status of their infant. They described alignment and misalignment with mFICare components relative to their personal parenting priorities and offered suggestions for improvement. Nurses were noted to play key roles in providing or facilitating parent support and encouragement to participate in mFICare and parenting activities. Conclusion: The mFICare program showed potential for parental acceptance and participation in US NICUs. Innovation: The mFICare model is an innovation in neonatal care that can advance the consistent delivery of NICU family-centered care planning and caregiving.Clinical Trial Registration:NCT03418870 01/02/2018.

Paving the way for COVID survivors' psychosocial rehabilitation: Mining topics, sentiments, and their trajectories over time from Reddit.

Objective: This study examined major themes and sentiments and their trajectories and interactions over time using subcategories of Reddit data. The aim was to facilitate decision-making for psychosocial rehabilitation. Materials and Methods: We utilized natural language processing techniques, including topic modeling and sentiment analysis, on a dataset consisting of more than 38,000 topics, comments, and posts collected from a subreddit dedicated to the experiences of people who tested positive for COVID-19. In this longitudinal exploratory analysis, we studied the dynamics between the most dominant topics and subjects' emotional states over an 18-month period. Results: Our findings highlight the evolution of the textual and sentimental status of major topics discussed by COVID survivors over an extended period of time during the pandemic. We particularly studied pre- and post-vaccination eras as a turning point in the timeline of the pandemic. The results show that not only does the relevance of topics change over time, but the emotions attached to them also vary. Major social events, such as the administration of vaccines or enforcement of nationwide policies, are also reflected through the discussions and inquiries of social media users. In particular, the emotional state (i.e., sentiments and polarity of their feelings) of those who have experienced COVID personally. Discussion: Cumulative societal knowledge regarding the COVID-19 pandemic impacts the patterns with which people discuss their experiences, concerns, and opinions. The subjects' emotional state with respect to different topics was also impacted by extraneous factors and events, such as vaccination. Conclusion: By mining major topics, sentiments, and trajectories demonstrated in COVID-19 survivors' interactions on Reddit, this study contributes to the emerging body of scholarship on COVID-19 survivors' mental health outcomes, providing insights into the design of mental health support and rehabilitation services for COVID-19 survivors.

A NIR-Light-Activated and Lysosomal-Targeted Pt (II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep-Seated Tumors.

Though platinum (Pt)-based complexes have been recently exploited as immunogenic cell death (ICD) inducers for activating immunotherapy, the effective activation of sufficient immune responses with minimal side effects in deep-seated tumors remains a formidable challenge. Herein, we propose the first example of a near-infrared (NIR) light-activated and lysosomal targeted Pt(II) metallacycle (1) as a supramolecular ICD inducer. 1 synergistically potentiates immunomodulatory response in deep-seated tumors via multiple-regulated approaches, involving NIR light excitation, boosted reactive oxygen species (ROS) generation, good selectivity between normal and tumor cells, and enhanced tumor penetration/retention capabilities. Specifically, 1 has excellent depth-activated ROS production (~ 7 mm), accompanied by strong anti-diffusion and anti-ROS quenching ability. In vitro experiments demonstrate that 1 exhibits significant cellular uptake and ROS generation in tumor cells as well as respective multicellular tumor spheroids. Based on these advantages, 1 induces a more efficient ICD in an ultralow dose (i.e., 5 µM) compared with the clinical ICD inducer-oxaliplatin (300 µM). In vivo, vaccination experiments further demonstrate that 1 serves as a potent ICD inducer through eliciting CD8+/CD4+ T cell response and Foxp3+ T cell depletion with negligible adverse effects. This study pioneers a promising avenue for safe and effective metal-based ICD agents in immunotherapy.

Gut microbiota is necessary for pair-housing to protect against post-stroke depression in mice.

The goal of this study is to investigate the role of microbiota-gut-brain axis involved in the protective effect of pair-housing on post-stroke depression (PSD). PSD model was induced by occluding the middle cerebral artery (MCAO) plus restraint stress for four weeks. At three days after MCAO, the mice were restrained 2 h per day. For pair-housing (PH), each mouse was pair housed with a healthy isosexual cohabitor for four weeks. While in the other PH group, their drinking water was replaced with antibiotic water. On day 35 to day 40, anxiety- and depression-like behaviors (sucrose consumption, open field test, forced swim test, and tail-suspension test) were conducted. Results showed pair-housed mice had better performance on anxiety- and depression-like behaviors than the PSD mice, and the richness and diversity of intestinal flora were also improved. However, drinking antibiotic water reversed the effects of pair-housing. Furthermore, pair-housing had an obvious improvement in gut barrier disorder and inflammation caused by PSD. Particularly, they showed significant decreases in CD8 lymphocytes and mRNA levels of pro-inflammatory cytokines (TNF-a, IL-1ß and IL-6), while IL-10 mRNA was upregulated. In addition, pair-housing significantly reduced activated microglia and increased Nissl's body in the hippocampus of PSD mice. However, all these improvements were worse in the pair-housed mice administrated with antibiotic water. We conclude that pair-housing significantly improves PSD in association with enhanced functions of microbiota-gut-brain axis, and homeostasis of gut microbiota is indispensable for the protective effect of pair-housing on PSD.

CircZNF609 sponges miR-135b to up-regulate SEMA3A expression to alleviate ox-LDL-induced atherosclerosis.

The initiation and progression of atherosclerotic plaque caused by abnormal lipid metabolism is one of the main causes of atherosclerosis (AS). Lipid droplet accumulation has become a novel research pointcut for AS treatment in recent years. In AS patients, miR-135b level was up-regulated relative to the normal cases, which showed negative correlations with the levels of Semaphorin 3A (SEMA3A) and circZNF609, separately. The U937-derived macrophages were cultured with ox-LDL to establish AS models in vitro. After that, the lipid accumulation, inflammation, mitochondrial dysfunction and cell death were evaluated by ORO, ELISA, RT-qPCR, western blot, JC-1 and FCM assays respectively. Transfection of the circZNF609 expression vector notably declined lipid accumulation, attenuated inflammation, reduced mitochondrial dysfunction and inhibited cell death in ox-LDL-stimulated cells. The direct binding of miR-135b to circZNF609 in vitro was confirmed using RIP assay, and SEMA3A expression was up-regulated by circZNF609 overexpression. After manipulating the endogenous expressions of circZNF609, miR-135b and SEMA3A, the above damages in ox-LDL-stimulated cells were rescued by inhibition of miR-135b expression and overexpression of circZNF609 or SEMA3A. Besides, the AS mice model was built to demonstrate the excessive lipid accumulation, increasing inflammation and cell death in AS pathogenesis according to the results of HE staining, ELISA and IHC assays, while these damages were reversed after overexpression of circZNF609 or SEMA3A. In AS models, overexpressed circZNF609 prevents the AS progression through depleting miR-135b expression and subsequent up-regulation of SEMA3A expression to overwhelm lipid accumulation, mitochondrial dysfunction and cell death.

Perioperative management of a patient with unexpectedly detected early-stage ovarian mucinous carcinoma combined with progressive bulbar paralysis: a case report and literature review.

BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.

Molecular Stratification and Treatment Monitoring of Lung Cancer Using a Small Extracellular Vesicle-Activated Nanocavity Architecture.

Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples (n = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.

The impact of recycling polyaluminium chloride and anionic polyacrylamide water treatment residuals on heavy metal adsorption in soils: implications for stormwater bioretention systems.

Despite the high adsorption capacity of polyaluminum chloride and anionic polyacrylamide water treatment residuals (PAC-APAM WTRs) for Pb2+, Cd2+, Cu2+, and Zn2+, their influence on the adsorption behavior of heavy metals in traditional bioretention soil media remains unclear. This study investigated the impact of PAC-APAM WTRs at a 20% weight ratio on the adsorption removal of Pb2+, Cd2+, Cu2+, and Zn2+ in three types of soils. The results demonstrated improved heavy metal adsorption in the presence of PAC-APAM WTRs, with enhanced removal observed at higher pH levels and temperatures. The addition of PAC-APAM WTRs augmented the maximum adsorption capacity for Pb2+ (from 0.98 to 3.98%), Cd2+ (from 0.52 to 10.99%), Cu2+ (from 3.69 to 36.79%), and Zn2+ (from 2.63 to 13.46%). The Langmuir model better described the data in soils with and without PAC-APAM WTRs. The pseudo-second-order model more accurately described the adsorption process, revealing an irreversible chemical process, although qe demonstrated improvement with the addition of PAC-APAM WTRs. This study affirms the potential of PAC-APAM WTRs as an amendment for mitigating heavy metal pollution in stormwater bioretention systems. Further exploration of the engineering application of PAC-APAM WTRs, particularly in field conditions for the removal of dissolved heavy metals, is recommended.

Overexpression of soybean GmDHN9 gene enhances drought resistance of transgenic Arabidopsis.

Soybean is one of the important oil crops and a major source of protein and lipids. Drought can cause severe soybean yields. Dehydrin protein (DHN) is a subfamily of LEA proteins that play an important role in plant responses to abiotic stresses. In this study, the soybean GmDHN9 gene was cloned and induced under a variety of abiotic stresses. Results showed that the GmDHN9 gene response was more pronounced under drought induction. Subcellular localization results indicated that the protein was localized in the cytoplasm. The role of transgenic Arabidopsis plants in drought stress response was further studied. Under drought stress, the germination rate, root length, chlorophyll, proline, relative water content, and antioxidant enzyme content of transgenic Arabidopsis thaliana transgenic genes were higher than those of wild-type plants, and transgenic plants contained less O2-, H2O2 and MDA contents. In short, the GmDHN9 gene can regulate the homeostasis of ROS and enhance the drought resistance of plants.

The oxytocin receptor is essential for the protective effect of pair housing on post-stroke depression in mice.

The beneficial effect of social interaction in mitigating the incidence of post-stroke depression (PSD) and ameliorating depressive symptoms has been consistently demonstrated through preclinical and clinical studies. However, the underlying relationship with oxytocin requires further investigation. In light of this, the present study aimed to explore the protective effect of pair housing on the development of PSD and the potential relationship with oxytocin receptors. The PSD model was induced by middle cerebral artery occlusion (MCAO) for 50 min, followed by 4-week isolated housing and restrained stress. Subsequently, each mouse in the pair-housing group (PH) was pair-housed with an isosexual healthy partner. Another group was continuously administrated fluoxetine (10 mg/Kg, i.p, once a day) for 3 weeks. To elucidate the potential role of oxytocin, we subjected pair-housed PSD mice to treatment with an oxytocin receptor (OXTR) antagonist (L368,889) (5 mg/Kg, i.p, once a day) for 3 weeks. At 31 to 32 days after MCAO, anxiety- and depressive-like behaviors were assessed using sucrose consumption, forced swim test, and tail-suspension test. The results showed that pair housing significantly improved post-stroke depression to an extent comparable to that of fluoxetine treatment. Furthermore, pair housing significantly decreased corticosterone in serum, increasing OXT mRNA expression in the hypothalamus. Treatment with L368,889 essentially reversed the effect of pair housing, with no discernible sex differences apart from changes in body weight. Pair housing increased hippocampal serotonin (5-HT), but treatment with L368,889 had no significant impact. Additionally, pair housing effectively reduced the number of reactive astrocytes and increased Nissl's body in the cortex and hippocampal CA3 regions. Correspondingly, treatment with L368,889 significantly reversed the changes in the Nissl's body and reactive astrocytes. Moreover, pair housing downregulated mRNA levels of TNF-α, IL-1ß, and IL-6 in the cortex caused by PSD, which was also reversed by treatment with L368,889. In conclusion, pair housing protects against the development of PSD depending on OXT and OXTR in the brain, with no significant divergence based on sex. These findings provide valuable insights into the potential of social interaction and oxytocin as therapeutic targets for PSD. Further research into the underlying mechanisms of these effects may contribute to the development of novel treatments for PSD.

Pectolinarigenin ameliorates osteoporosis via enhancing Wnt signaling cascade in PPARß-dependent manner.

BACKGROUND: Osteoporosis is a prevalent metabolic bone disease in older adults. Peroxisome proliferator-activated receptor ß (PPARß), the most abundant PPAR isotype expressed in bone tissues, plays a critical role in regulating the energy metabolism of osteoblasts. However, the botanical compounds targeting PPARß for the treatment of osteoporosis remain largely unexplored. PURPOSE: To discover a potent PPARß agonist from botanical compounds, as well as to investigate the anti-osteoporosis effects and to elucidate the underlying mechanisms of the newly identified PPARß agonist. METHODS: The PPARß agonist effects of botanical compounds were screened by an in vitro luciferase reporter gene assay. The PPARß agonist effects of pectolinarigenin (PEC) in bone marrow mesenchymal stromal cells (BMSCs) were validated by Western blotting. RNA-seq transcriptome analyses were conducted to reveal the underlying osteoporosis mechanisms of PEC in BMSCs. The PPARß antagonist (GSK0660) and Wnt signaling inhibitor (XAV969) were used to explore the role of the PPARß and Wnt signaling cascade in the anti-osteoporosis effects of PEC. PEC or the PEG-PLGA nanoparticles of PEC (PEC-NP) were intraperitoneally administrated in both wild-type mice and ovariectomy-induced osteoporosis mice to examine its anti-osteoporotic effects in vivo. RESULTS: PEC, a newly identified naturally occurring PPARß agonist, significantly promotes osteogenic differentiation and up-regulates the osteogenic differentiation-related genes (Runx2, Osterix, and Bmp2) in BMSCs. RNA sequencing and functional gene enrichment analysis suggested that PEC could activate osteogenic-related signaling pathways, including Wnt and PPAR signaling pathways. Further investigations suggested that PEC could enhance Wnt/ß-catenin signaling in a PPARß-dependent manner in BMSCs. Animal tests showed that PEC-NP promoted bone mass and density, increased the bone cell matrix protein, and accelerated bone formation in wild-type mice, while PEC-NP also played a preventive role in ovariectomy-induced osteoporosis mice via maintaining the expression level of bone cell matrix protein, balancing the rate of bone formation, and slowing down bone loss. Additionally, PEC-NP did not cause any organ injury and body weight loss after long-term use (11 weeks). CONCLUSION: PEC significantly promotes bone formation and reduces bone loss in both BMSCs and ovariectomy-induced osteoporosis mice via enhancing the Wnt signaling cascade in a PPARß-dependent manner, providing a new alternative therapy for preventing estrogen deficiency-induced osteoporotic diseases.

Gastric Type Endocervical Adenocarcinoma With Concurrent High-Grade Squamous Intraepithelial Lesion: A Clinicopathologic Study of Three Patients.

OBJECTIVE: We investigate gastric-type endocervical adenocarcinoma (ECA), a prominent HPV-independent adenocarcinoma, and its coexistence with high-grade squamous intraepithelial lesion (HSIL) through the examination of three such tumors. METHODS: In this study, we conducted an in-depth review of three patients with gastric-type ECA, each associated with high-risk HPV infection as detected on Pap smears. We detailed the clinical and pathological features of each patient and utilized RNAscope for high-risk HPV testing to ascertain HPV status in both gastric-type ECA and HSIL components. Immunohistochemistry with p16, p53, and other biomarkers was also applied. RESULTS: The gastric-type ECA component, characterized by well-differentiated glands with abundant, clear to eosinophilic cytoplasm, distinct cellular borders, and pale nuclei with conspicuous nucleoli, tested negative for both p16 and high-risk HPV, unlike the concurrent HSIL components which were positive. Additionally, two tumors showed aberrant p53 protein expression in the gastric-type ECA areas, and elevated carbohydrate antigen19-9 levels were noted in two patients. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy, supplemented by chemotherapy and/or radiation, with disease-free intervals of 24, 12, and 40 months post-treatment, respectively. CONCLUSION: This study highlights the critical need for meticulous diagnostic protocols that combine morphological examination, immunohistochemistry, and HPV RNA in situ hybridization. The rarity of gastric-type ECA coexisting with HPV infection underscores the necessity for continuous research and vigilant monitoring in the field of gynecological oncology.

All in the family: The complementary protective roles of spousal and other family support for Chinese immigrant mothers' life satisfaction over time.

The demand-resources model of stress posits that parenting tasks and expectations of mothers that exceed their resources are likely to tax their psychological well-being. Social and instrumental support from spouse or family may help alleviate the negative effects of parenting stress on mothers' psychological well-being. However, parenting stress and its impact have been less studied among immigrant mothers. Moreover, the sources of family support (i.e., spousal and other family members) might interactively affect mothers' well-being in the face of parenting stress. Therefore, the present study aimed to examine whether support from the spouse and other family members jointly buffers against the long-term psychological effects of parenting stress on Chinese immigrant mothers' life satisfaction. Data were collected from 273 Chinese American mothers at two time points separated by 6 months. A three-way interaction was conducted to examine the complementary protective effect of perceived support mothers received from their spouses and their other family members combined. Results showed that after controlling for the covariates, parenting stress was only longitudinally associated with changes in maternal life satisfaction when support from both spouse and other family members was low. Our findings highlight the complementary protective effects of spousal support and nonspouse family members' support in alleviating parenting stress of mothers and its adverse impact on lowering mothers' life satisfaction 6 months later. Theoretical and applied implications of these findings are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Urine-derived stem cells: Promising advancements and applications in regenerative medicine and beyond.

Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.

High Accuracy of Clinical Verification of Electrohydrodynamic-Driven Nanobox-on-Mirror Platform for Molecular Identification of Respiratory Viruses.

The molecular detection of multiple respiratory viruses provides evidence for the rational use of drugs and effective health management. Herein, we developed and tested the clinical performance of an electrohydrodynamic-driven nanobox-on-mirror platform (E-NoM) for the parallel, accurate, and sensitive detection of four respiratory viral antigens. The E-NoM platform uses gold-silver alloy nanoboxes as the core material with the deposition of a silver layer as a shell on the core surfaces to amplify and enable a reproducible Raman signal readout that facilitates accurate detection. Additionally, the E-NoM platform employs gold microelectrode arrays as the mirror with electrohydrodynamics to manipulate the fluid flow and enhance molecular interactions for an improved biosensing response. The presence of viral antigens binds the nanobox-based core-shell nanostructure on the gold microelectrode and creates the nanocavity with extremely strong "hot spots" to benefit sensitive analysis. Significantly, in a large clinical cohort with 227 patients, the designed E-NoM platform demonstrates the capability of screening respiratory infection with achieved clinical specificity, sensitivity, and accuracy of 100.0, 96.48, and 96.91%, respectively. It is anticipated that the E-NoM platform can find a position in clinical usage for respiratory disease diagnosis.

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle.

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (∼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 µM) compared to the conventional anticancer agent, oxaliplatin (300 µM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8+ T cell responses and depleting Foxp3+ T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.