Cystathionine-ß-synthase (CBS)/H2S system promotes lymph node metastasis of esophageal squamous cell carcinoma (ESCC) by activating SIRT1.

Lymph node metastasis is a key factor of death and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Previous studies have demonstrated that Cystathionine-ß-synthase (CBS)/H2S system plays important roles in progression of various cancer. However, the function and mechanism of CBS/H2S system in lymph node metastasis of ESCC remains unclear. Here, we found that CBS was highly expressed in human ESCC tissues and closely associated with lymph node metastasis in ESCC patients. Functional studies demonstrated that CBS could significantly promote lymph node metastasis of ESCC tumor cells. In vitro, CBS knockdown inhibited tumor cell proliferation, migration and invasion, whereas CBS overexpression produced the opposite results. In vivo, downregulation of CBS distinctly inhibited ESCC tumor growth and lymphatic metastasis, as evidenced by the decreased size and weight of tumor and popliteal lymph node. Meanwhile, we also found high expression of CBS-induced ESCC angiogenesis and lymphangiogenesis in vitro and in vivo by upregulating VEGF, VEGF-C, and VEGF-D. Mechanistically, CBS up-regulated the expression of SIRT1 and thus interrupted the Notch1/Hes1 axis, which plays a crucial role in lymph node metastasis of ESCC. Moreover, it was demonstrated that H2S derived from CBS-activated SIRT1 via increasing the NAD+/NADH ratio and promoting the phosphorylation of SIRT1. In addition, H2S derived from CBS also enhanced SIRT1 protein stability. Taken together, these data show that the high expression of CBS/H2S system promotes ESCC lymph node metastasis via activating SIRT1 signaling pathway and CBS could serve as a potential therapeutic target for clinical intervention in ESCC.

MicroRNA-506 ameliorates breast cancer-induced osteolytic bone metastasis via the NFATc-1 signaling pathway.

Breast cancer is becoming a common life-threatening disease, especially in women, along with higher incidence and mortality. MicroRNA (miR)-506 was reported to participate in breast cancer progression, while the role of miR-506 in breast cancer-induced osteolytic bone metastasis is unclear. In the present study, we found significant downregulation of miR-506 in breast cancer tissues and cell lines. Overexpression of miR-506 notably reduced the proliferative, migratory and invasive rates of MCF7 and MDA-MB-231 cells, and reduced the production of inflammatory factors IL-6 and TNF-α in MCF7 cells. Moreover, overexpression of miR-506 obviously inhibited tumor growth in an in vivo animal model. In addition, overexpression of miR-560 efficiently attenuated breast cancer-induced osteolysis in vivo, which was characterized by increased bone volume/total volume (BT/TV), trabecular number (Tb. N), and trabecular thickness (Tb. Th), as well as the reduced trabecular separation (Tb. Sp). The nuclear factor of activated T cell cytoplasmic 1 (NFATc1) was identified as a downstream target of miR-506, and overexpression of miR-506 could inhibit breast cancer progression by targeting NFATc1. Furthermore, our results showed that NFATc-1 might participate in the inhibition of miR-506 on breast cancer-induced osteolysis. In conclusion, our findings provide insights into understanding the pathogenesis of breast cancer and breast cancer-induced osteolytic bone metastasis, and miR-506 might serve as a novel biomarker for this disease.

One-Pot Heterointerfacial Metamorphosis for Synthesis and Control of Widely Varying Heterostructured Nanoparticles.

Despite remarkable facileness and potential in forming a wide variety of heterostructured nanoparticles with extraordinary compositional and structural complexity, one-pot synthesis of multicomponent heterostructures is largely limited by the lack of fundamental mechanistic understanding, designing principles, and well-established, generally applicable chemical methods. Herein, we developed a one-pot heterointerfacial metamorphosis (1HIM) method that allows heterointerfaces inside a particle to undergo multiple equilibrium stages to form a variety of highly crystalline heterostructured nanoparticles at a relatively low temperature (<100 °C). As proof-of-concept experiments, it was shown that widely different single-crystalline semiconductor-metal anisotropic nanoparticles with synergistic chemical, spectroscopic, and band-gap-engineering properties, including a series of metal-semiconductor nanoframes with high structural and compositional tunability, can be formed by using the 1HIM approach. 1HIM offers a new paradigm to synthesize previously unobtainable or poorly controllable heterostructures with unique or synergistic properties and functions.

Near-Infrared Voltage Nanosensors Enable Real-Time Imaging of Neuronal Activities in Mice and Zebrafish.

Optical voltage sensors with the ability to monitor neuronal activities are invaluable tools for studying information processing of the brain. However, the current genetically encoded voltage indicators usually require high-power visible light for excitation and are limited to genetically addressable model animals. Here, we report a near-infrared (NIR)-excited nongenetic voltage nanosensor that achieves stable recording of neuronal membrane potential in intact animals. The nanosensor is composed of a Förster resonance energy transfer (FRET) pair, the outer membrane-anchored upconversion nanoparticle (UCNP), and the membrane-embedded dipicrylamine (DPA). The negative charge of DPA allows membrane potential fluctuation to affect the distance between the DPA and UCNP, therefore changing the FRET efficiency. Consequently, the emission intensity of the nanosensor can report the membrane potential. Using the nanosensor, we monitor not only electrically evoked changes in the membrane potential of cultured cells but also sensory responses of neurons in intact zebrafish and brain state-modulated subthreshold activities of cortical neurons in intact mice.

Cancer cell nucleus-targeting nanocomposites for advanced tumor therapeutics.

Tumor therapeutic efficacy is determined, to a great extent, by the delivery efficiency of therapeutic drugs to their final targets. The cell nucleus has been proven to be the main interaction site for most therapeutic agents such as anticancer drugs, genes, free radicals, and heat. Therefore, it is highly expected that cell nucleus-targeting or nuclear membrane-penetrating nanotherapeutics would provide a more effective strategy than ordinary cell membrane-targeting ones for benefiting precise nanomedicine in humans' battles against cancer. This tutorial review presents a summary of the most recent progress achieved in the design, synthesis, and application of cell nucleus-targeting nanotherapeutics. We first discuss a number of design principles involved in cell nucleus-targeting nanotherapeutics, including size control, shape regulation, and surface modification. Next, we demonstrate the diverse applications of cell nucleus-targeting nanotherapeutics ranging from chemotherapy, gene therapy, photodynamic therapy, photothermal therapy to synergistic therapy. Moreover, a number of typical nanotherapeutics designed for enhanced therapeutic efficacy by targeting other subcellular organelles (such as mitochondria, lysosomes, and endoplasmic reticulum) are also briefly discussed. Finally, perspectives and challenges in this research field are proposed, in the hope of accelerating their translation into the clinic.

Real-time in vivo quantitative monitoring of drug release by dual-mode magnetic resonance and upconverted luminescence imaging.

Insufficient or excess drug doses, due to unknown actual drug concentrations at the focus, are one of the main causes of chemotherapy failure for cancers. In this regard, the real-time monitoring of the release of anticancer drugs from nanoparticle drug delivery systems is of crucial importance, but it remains a critical and unsolved challenge. Herein, we report the proposal and development of a novel concept of real-time monitoring of NIR-triggered drug release in vitro and in vivo by using simultaneous upconverted luminescence (UCL) and magnetic resonance (MR) imaging. Such a monitoring strategy features the high sensitivity of UCL and the high-resolution, noninvasiveness, and tissue-depth-independence of MR imaging. The dual-mode real-time and quantitative monitoring of drug release can be applied to determine online the drug concentrations in vivo in the tissue regions of interest and, therefore, to avoid insufficient or excess drug dosings.

Research progress on insomnia treated by traditional Chinese medicine and acupuncture based on microbial-gut-brain axis theory.

Insomnia, as one of the emotional diseases, has been increasing in recent years, which has a great impact on people's life and work. Therefore, researchers are eager to find a more perfect treatment. The microbiome-gut-brain axis is a new theory that has gradually become popular abroad in recent years and has a profound impact in the field of insomnia. In recent years, traditional Chinese medicine (TCM) has played an increasingly important role in the treatment of insomnia, especially acupuncture and Chinese herbal medicine. It is the main method of TCM in the treatment of insomnia. This paper mainly reviews the combination degree of "microorganism-gut-brain axis" theory with TCM and acupuncture under the system of TCM. To explore the mechanism of TCM and acupuncture in the treatment of insomnia under the guidance of "microorganism-gut-brain axis" theory, in order to provide a new idea for the diagnosis and treatment of insomnia.

Mechanism and future prospect of treatment of facial paralysis caused by herpes zoster virus infection with acupuncture combined with medicine: A review.

Herpes zoster virus infectious facial paralysis is caused by the reactivation and replication of varicella-zoster virus, which leads to herpetic inflammatory lesions, resulting in peripheral facial paralysis associated with herpes rash in the auricle and external ear, and vestibular cochlear dysfunction. It is also known as Ramsey-Hunter syndrome (Hunt syndrome). Facial paralysis caused by herpes zoster is difficult to cure due to its easy loss of treatment and mistreatment. Cause a greater burden on the patient's body and mind. However, the treatment of Western medicine has lagged behind and there are many adverse reactions, which cannot be completely cured, and new alternatives are urgently needed. This article briefly reviews the advantages and disadvantages of modern medical treatment of Hunt syndrome. This paper expounds the unique ideas of traditional Chinese medicine in the treatment of Hunt syndrome from the perspectives of antiviral, antibacterial, improving blood circulation, protecting cardiovascular, cerebrovascular, and nerve. This article discusses the superiority of traditional Chinese medicine in the treatment of Hunt syndrome from 2 aspects of Chinese medicine therapy and acupuncture therapy, and points out the feasibility of combined treatment of acupuncture and traditional Chinese medicine. So as to provide a new treatment for Hunt syndrome.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine.

Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.

Network Pharmacology and Experimental Analysis to Explore the Effect and Mechanism of Modified Buyang Huanwu Decoction in the Treatment of Diabetic Nephropathy.

Purpose: Preventing and treating diabetic nephropathy (DN) are global challenges due to the complexity and diversity of its causes and manifestations. It is important to find effective medications to treat DN. Patients and Methods: Gene expression files of DN were downloaded from the GEO database to identify the differentially expressed genes. Network pharmacology and molecular docking were used to explore the possible mechanisms of modified Buyang Huanwu Decoction (mBHD) in treating DN. Biochemical, histopathological, and real-time PCR analyses were conducted in both in vivo and in vitro DN models to investigate the effects of mBHD. Results: A total of 336 active ingredients and 124 potential targets of mBHD associated with DN were identified. Among them, 8 hub genes were found to be important targets for mBHD in treating DN and were significantly correlated with the infiltration status of six immune cells. Partially, the active ingredients of mBHD demonstrated good stability in binding to CASP3 and TP53. mBHD treatment significantly reduced levels of total cholesterol, triglyceride, blood urea nitrogen, serum creatinine, and microalbumin in db/db mice. HE and Masson's staining results showed that mBHD attenuated renal injury in db/db mice. Additionally, mBHD treatment could significantly alter the expression of CASP3, CCL2, TP53, ALB, and HMOX1. Conclusion: mBHD may be involved in the treatment of DN through multiple ingredients, targets, and pathways. In addition, mBHD could alleviate renal injury in db/db mice, possibly involving CASP3, CCL2, TP53, ALB, and HMOX1.

Empagliflozin attenuating renal interstitial fibrosis in diabetic kidney disease by inhibiting lymphangiogenesis and lymphatic endothelial-to-mesenchymal transition via the VEGF-C/VEGFR3 pathway.

Renal interstitial fibrosis (RIF) is a significant pathological change in diabetic kidney disease (DKD) that can be induced by endothelial-to-mesenchymal transition (EndMT). Lymphangiogenesis, mediated by the vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) pathway, plays a crucial role in the development of RIF in DKD. Although numerous studies have demonstrated the efficacy of empagliflozin in treating renal injury, its effects on lymphangiogenesis in DKD-related RIF and the underlying mechanisms remain unclear. In the present study, significant lymphangiogenesis was assessed in the renal interstitium of patients with DKD. We subsequently explored the relationship between DKD-related RIF and lymphangiogenesis in mouse models, high-glucose (HG)-stimulated renal HK-2 cell lines, and human lymphatic endothelial cells (hLECs). Additionally, we evaluated the effects of empagliflozin on these processes. The results revealed that HG induces lymphangiogenesis, which exacerbates RIF by promoting inflammatory responses. Furthermore, hLECs directly contributed to the progression of DKD-related RIF through EndMT. Further analysis revealed that tubular epithelial cells (TECs) act as effector cells for VEGF-C, with the epithelial-to-mesenchymal transition (EMT) of TECs occurring concurrently with the EndMT of lymphatic vessels. Empagliflozin inhibited RIF in DKD by suppressing the VEGF-C/VEGFR3 pathway and reducing lymphangiogenesis. In conclusion, this study elucidates the interplay between lymphangiogenesis, EndMT, and RIF in DKD and provides new insights into the mechanism by which empagliflozin treats DKD.

Cascade Catalytic Nanoparticles Selectively Alkalize Cancerous Lysosomes to Suppress Cancer Progression and Metastasis.

Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (•OH) in the presence of excessive H+ and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert •OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe.

Mechanism of Schwann cells in diabetic peripheral neuropathy: A review.

Diabetic peripheral neuropathy (DPN) is the most common neuropathy in the world, mainly manifested as bilateral symmetry numbness, pain or paresthesia, with a high rate of disability and mortality. Schwann cells (SCs), derived from neural ridge cells, are the largest number of glial cells in the peripheral nervous system, and play an important role in DPN. Studies have found that SCs are closely related to the pathogenesis of DPN, such as oxidative stress, endoplasmic reticulum stress, inflammation, impaired neurotrophic support and dyslipidemia. This article reviews the mechanism of SCs in DPN.

Study on the active ingredients and mechanism of Jiaotai Pill in the treatment of primary insomnia based on network pharmacology and GEO statistics: A review.

OBJECTIVE: To explore the active components and mechanism of Jiaotai Pill (JTP) in the treatment of primary insomnia (PI) based on gene expression omnibus. METHODS: The main active components of Jiaotai Pills were obtained by TCMSP and literature mining, and the targets of the active components of Jiaotai Pills were predicted. The targets were verified and standardized by Uniprot database. PI-related targets were obtained from GeneCards, OMIM, DrugBank, PharmGKB, and TTD databases. Obtaining an intersection action target point of the Jiaotai pill and the PI by using a Venny diagram; Gene chip data (GSE208668) was downloaded from gene expression omnibus database, and then gene probe enrichment analysis (GSEA) was used to screen the differentially expressed genes between PI patients and normal controls, and molecular docking was used to virtually verify the screened differentially expressed genes with potential active compounds. RESULTS: 21 active components and 263 potential targets of Jiaotai Pill were screened by database analysis and literature mining, 112 of which were intersected with PI. Molecular docking results showed that quercetin, EGCG, kaempferol, R-kanatin, stigmasterol, berberine and other core active components had good docking activity with related differential genes. CONCLUSION: Jiaotai Pill can regulate the release of inflammatory factors through multiple active ingredients, multiple disease targets, multiple biological pathways and multiple pathways to achieve the purpose of treating PI, which provides a theoretical basis for the clinical treatment of PI and broadens the clinical use of Jiaotai Pill.

Efficacy of traditional Chinese exercises in improving anthropometric and biochemical indicators in overweight and obese subjects: A systematic review and meta-analysis.

BACKGROUND: The efficacy of traditional Chinese exercise (TCE)-based intervention in the improvement of anthropometric and biochemical indicators in overweight and obese patients is controversial. In this regard, the aim of this review was to summarize the evidence of TCE interventions to evaluate their effectiveness on the anthropometric and biochemical indicators of overweight and obese patients. METHOD: Five databases were systematically searched for relevant articles published from inception to October 2022. Randomized controlled trials examining TCE intervention in overweight and obese patients The treatment effects were estimated using a random-effect meta-analysis model with standardized mean differences (Hedges' g). The categorical and continuous variables were used to conduct moderator analyses. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (identifier CRD42022377632). RESULT: Nine studies involving a total of 1297 participants were included in the final analysis. In the anthropometric indicators outcomes, the meta-analytic findings revealed large and significant improvements in body mass index (g = 1.44, 95% confidence interval [CI] = 1.27-1.61, P = .000, I2 = 99%), weight (g = 1.47, 95% CI = 1.25-1.68, P = .000, I2 = 95%), fat percentage (g = 1.22, 95% CI = 0.52-1.93, P = .000, I2 = 93%), and small and significant improvements in waist circumference (g = 0.38, 95% CI = 0.21-0.54, P = .000, I2 = 99%). In the biochemical indicators outcomes, the findings revealed large and significant improvements in low density lipoprotein (g = 2.08, 95% CI = 1.80-2.37, P = .000, I2 = 98%), moderate and significant improvements in triglyceride (g = 0.69, 95% CI = 0.56-0.81, P = .000, I2 = 96%), small and significant improvements in total cholesterol (g = 0.37, 95% CI = 0.19-0.54, P = .000, I2 = 77%), and high-density lipoprotein (g = -0.71, 95% CI = -0.86 to 0.57, P = .000, I2 = 99%). The moderator shows that the effects of TCE on anthropometric and biochemical indicators were moderated by frequency of exercise, exercise duration, and type of control group. CONCLUSION: TCE intervention is a beneficial non-pharmacological approach to improving anthropometric and biochemical indicators in overweight and obese subjects, especially in body mass index, weight, fat percentage, triglyceride, and low-density lipoprotein. The clinical relevance of our findings is pending more extensive trials and more rigorous study designs to strengthen the evidence.

Clinical study of "Jiaotai Pill" combined with head massage with 5-tone rhythm on insomnia patients of heart-kidney disharmony type.

OBJECTIVE: To explore the curative effect of "Jiaotai Pill" combined with head rhythmic massage consistent with 5-tone rhythm on insomnia of heart-kidney disharmony type. METHODS: Sixty patients with insomnia in massage clinic and ward were randomly divided into treatment group A (30 cases) and treatment group B (30 cases). Patients in group A were treated with traditional head massage combined with oral estazolam tablets. Group B was treated with "Jiaotai Pill" combined with head rhythmic massage therapy consistent with 5-tone rhythm. After 2 weeks of treatment, the scores of Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index and Traditional Chinese Medicine Symptom Scale, as well as the expression changes of interleukin (IL)-6 and IL-8 in serum were compared between the 2 groups before and after treatment. RESULTS: After 2 weeks of treatment, the total effective rate of group B was 93. 33%, which was significantly higher than that of group A (66. 67%) (P < .05). After treatment, the scores of Hamilton Anxiety Scale, PQSI, insomnia severity index and traditional Chinese medicine symptom scores were significantly decreased in both groups, and the decrease in group B was more significant than that in group A (P < .05). After treatment, the serum levels of IL-6 and IL-8 were significantly decreased in both groups, and the decrease in group B was greater than that in group A, the difference was statistically significant (P < .05). CONCLUSION: The overall efficacy of Jiaotai Pill combined with head massage therapy consistent with 5-tone rhythm is significantly better than that of traditional massage combined with 5-element music therapy for insomnia patients with heart-kidney disharmony.

Value of internet of things-based diagnosis-treatment model in improving the quality of medical services during COVID-19 outbreak.

OBJECTIVE: To demonstrate the value of Internet of things (IoT)-based diagnosis-treatment model in improving medical service quality during the novel coronavirus pneumonia (COVID-19) outbreak. METHODS: In this retrospective analysis, 483 patients with chronic diseases treated between January 2020 and March 2021 were selected and grouped as follows based on different intervention methods: a research group (the Res group) with 229 patients that were given IoT-based diagnosis and treatment, and a control group (the Con group) with 254 patients that were treated with routine diagnosis and treatment. The qualified rate of medical records, the missing rate of medical records, and the incidence of doctor-patient disputes were compared between the two groups. In addition, investigations were made regarding patients' daily living ability, psychological state, health behavior, self-care ability, quality of life, as well as treatment satisfaction. RESULTS: There was no difference in the qualified rate of medical records between the Res group and the Con group (P>0.05), but the missing rate of medical records and the incidence of doctor-patient disputes were lower in the Res group (both P<0.05). An obviously improved living ability was observed in both groups after the treatment (both P<0.05), with no statistical significance between groups (P>0.05). Besides, the Res group presented lower scores of SAS and SDS but higher scores of SRAHP, ES-CA and SF-36 than the Con group after treatment (all P<0.05). Finally, according to the satisfaction survey, more patients in the Res group were very satisfied but fewer cases were dissatisfied with the medical service they received as compared with the Con group (both P<0.05). CONCLUSIONS: The IoT-based diagnosis-treatment model can effectively improve the quality of medical services and patients' self-care ability, which is extremely important and promising for addressing the current medical limitations during the COVID-19 epidemic.

Research progress on the treatment of perimenopausal insomnia with Chaihu Jia Longgu Muli decoction based on brain-intestine-bacteria axis: A review.

With the progress and rapid societal development, women are confronted with multifaceted pressures in their lives, encompassing familial and other domains. Furthermore, during the perimenopausal phase, endocrine equilibrium is disrupted, leading to the emergence of psychological and physiological health challenges. Insomnia is a prevalent symptom among perimenopausal individuals. The brain-gut-bacteria axis assumes a pivotal role in the prevention, diagnosis, and management of perimenopausal insomnia. Chaihu Jia Longgu Muli decoction is a commonly prescribed remedy for addressing perimenopopausal insomnia. Consequently, this paper aims to investigate the interplay between the brain-gut-bacteria axis, intestinal microbiota, and the pathogenesis of perimenopausal insomnia. The study focuses on examining the regulatory effects of Chaihu Jia Longgu Muli decoction on the nervous system, intestinal microbiota, and the hypothalamus-pituitary-adrenal axis. Additionally, it explores the mechanisms underlying Hujia Longgu Muli decoction in mitigating perimenopausal insomnia.

Co-Delivery of Metabolic Modulators Leads to Simultaneous Lactate Metabolism Inhibition and Intracellular Acidification for Synergistic Cancer Therapy.

Simultaneous lactate metabolism inhibition and intracellular acidification (LIIA) is a promising approach for inducing tumor regression by depleting ATP. However, given the limited efficacy of individual metabolic modulators, a combination of various modulators is required for highly efficient LIIA. Herein, a co-delivery system that combines lactate transporter inhibitor, glucose oxidase, and O2 -evolving nanoparticles is proposed. As a vehicle, a facile room-temperature synthetic method for large-pore mesoporous silica nanoparticles (L-MSNs) is developed. O2 -evolving nanoparticles are then conjugated onto L-MSNs, followed by immobilizing the lactate transporter inhibitor and glucose oxidase inside the pores of L-MSNs. To load the lactate transporter inhibitor, which is too small to be directly loaded into the large pores, it is encapsulated in albumin by controlling the albumin conformation before being loaded into L-MSNs. Notably, inhibiting lactate efflux shifts the glucose consumption mechanism from lactate metabolism to glucose oxidase reaction, which eliminates glucose and produces acid. This leads to synergistic LIIA and subsequent ATP depletion in cancer cells. Consequently, L-MSN-based co-delivery of modulators for LIIA shows high anticancer efficacy in several mouse tumor models without toxicity in normal tissues. This study provides new insights into co-delivery of small-molecule drugs, proteins, and nanoparticles for synergistic metabolic modulation in tumors.

The prognostic value and response to immunotherapy of immunogenic cell death-associated genes in breast cancer.

Breast cancer (BRCA) remains the most prevalent cancer worldwide and the tumor microenvironment (TME) has been discovered to exert a wide influence on the overall survival and therapeutic response. Numerous lines of evidence reported that the effects of immunotherapy of BRCA were manipulated by TME. Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is capable of fueling adaptive immune responses and aberrant expression of ICD-related genes (ICDRGs) can govern the TME system by emitting danger signals or damage-associated molecular patterns (DAMPs). In the current study, we obtained 34 key ICDRGs in BRCA. Subsequently, using the transcriptome data of BRCA from the TCGA database, we constructed a risk signature based on 6 vital ICDRGs, which had a good performance in predicting the overall survival of BRCA patients. We also examined the efficacy of our risk signature in the validation dataset (GSE20711) in the GEO database and it performed excellently. According to the risk model, patients with BRCA were divided into high-risk and low-risk groups. Also, the unique immune characteristics and TME between the two subgroups and 10 promising small molecule drugs targeting BRCA patients with different ICDRGs risk have been investigated. The low-risk group had good immunity indicated by T cell infiltration and high immune checkpoint expression. Moreover, the BRCA samples could be divided into three immune subtypes according to immune response severity (ISA, ISB, and ISC). ISA and ISB predominated in the low-risk group and patients in the low-risk group exhibited a more vigorous immune response. In conclusion, we developed an ICDRGs-based risk signature that can predict the prognosis of BRCA patients and offer a novel therapeutic strategy for immunotherapy, which would be of great significance in the BRCA clinical setting.