Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

A fully autonomous robotic ultrasound system for thyroid scanning.

The current thyroid ultrasound relies heavily on the experience and skills of the sonographer and the expertise of the radiologist, and the process is physically and cognitively exhausting. In this paper, we report a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nod- ules. In this system, human skeleton point recognition, reinforcement learning, and force feedback are used to deal with the difficulties in locating thyroid targets. The orientation of the ultrasound probe is adjusted dynamically via Bayesian optimization. Experimental results on human participants demonstrated that this system can perform high-quality ultrasound scans, close to manual scans obtained by clinicians. Additionally, it has the potential to detect thyroid nodules and provide data on nodule characteristics for American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) calculation.

Enhancing AsH3 Detoxification via Electron-Deficient [NiIII-OH (µ-O)] in a Nickel-Modified NaY Zeolite: A Pathway toward As0 Products.

The transformation of toxic arsine (AsH3) gas into valuable elemental arsenic (As0) from industrial exhaust gases is important for achieving sustainable development goals. Although advanced arsenic removal catalysts can improve the removal efficiency of AsH3, toxic arsenic oxides generated during this process have not received adequate attention. In light of this, a novel approach for obtaining stable As0 products was proposed by performing controlled moderate oxidation. We designed a tailored Ni-based catalyst through an acid etching approach to alter interactions between Ni and NaY. As a result, the 1Ni/NaY-H catalyst yielded an unprecedented proportion of As0 as the major product (65%), which is superior to those of other reported catalysts that only produced arsenic oxides. Density functional theory calculations clarified that Ni species changed the electronic structure of oxygen atoms, and the formed [NiIII-OH (µ-O)] active centers facilitated the adsorption of AsH2*, AsH*, and As* reaction intermediates for As-H bond cleavage, thereby decreasing the direct reactivity of oxygen with the arsenic intermediates. This work presents pioneering insights into inhibiting excessive oxidation during AsH3 removal, demonstrating potential environmental applications for recovery of As0 from toxic AsH3.

Lysosome passivation triggered by silver nanoparticles enhances subcellular-targeted drug therapy.

Frequently, subcellular-targeted drugs tend to accumulate in lysosomes after cellular absorption, a process termed the lysosomal trap. This accumulation often interferes with the drug's ability to bind to its target, resulting in decreased efficiency. Existing methods for addressing lysosome-induced drug resistance mainly involve improving the structures of small molecules or enveloping drugs in nanomaterials. Nonetheless, these approaches can lead to changes in the drug structure or potentially trigger unexpected reactions within organisms. To address these issues, we introduced a strategy that involves inactivating the lysosome with the use of Ag nanoparticles (Cy3.5@Ag NPs). In this method, the Cy3.5@Ag NPs gradually accumulate inside lysosomes, leading to permeation of the lysosomal membrane and subsequent lysosomal inactivation. In addition, Cy3.5@Ag NPs also significantly affected the motility of lysosomes and induced the occurrence of lysosome passivation. Importantly, coincubating Cy3.5@Ag NPs with various subcellular-targeted drugs was found to significantly increase the efficiency of these treatments. Our strategy illustrates the potential of using lysosomal inactivation to enhance drug efficacy, providing a promising therapeutic strategy for cancer.

Chiral Supramolecular Nanofibers Regulated Tumor-Derived Exosomes Secretion for Constructing an Anti-Tumor Extracellular Microenvironment.

Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of L/D -phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion.

Tumor keratin 15 expression links with less extent of invasion and better prognosis in papillary thyroid cancer patients receiving tumor resection.

OBJECTIVE: Keratin 15 (KRT15) is identified as a useful biomarker in several solid tumors, while its clinical role in papillary thyroid cancer (PTC) remains unknown. Herein, this study is intended to explore the correlation of tumor KRT15 with clinical features and survival in PTC patients who received tumor resection. METHODS: This study retrospectively screened 350 PTC patients who received tumor resection and 50 thyroid benign lesions (TBL) patients. KRT15 in formalin-fixed paraffin-embedded lesion specimens of all subjects was detected by immunohistochemistry (IHC). RESULTS: KRT15 was reduced in PTC patients compared to TBL patients (P < 0.001). Furthermore, KRT15 was negatively associated with tumor size (P = 0.017), extrathyroidal invasion (P = 0.007), pathological tumor (pT) stage (P < 0.001), and postoperative radioiodine application (P = 0.008) in PTC patients. Regarding prognostic value, high KRT15 (cut-off by an IHC value of 3) is linked with prolonged accumulating disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.008) in PTC patients. Also, the multivariate Cox regression model showed that high KRT15 (vs. low) was an independent factor for longer DFS (hazard ratio = 0.433, P = 0.049), but not for OS (P > 0.050) in PTC patients. Subgroup analyses revealed that KRT15 possessed a better prognostic value in PTC patients with age ≥ 55 years, tumor size > 4 cm, pathological node stage 1, or pathological tumor-node-metastasis stage ≤ 2 (all P < 0.050). CONCLUSION: Increased tumor KRT15 associates with a lower invasive degree, prolonged DFS, and OS, revealing its prognostic utility in PTC patients undergoing tumor resection.

Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema.

Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA-loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA- loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L-type hydrogels are found to have preferable drug penetration over D-type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration.

Drug monomers from Salvia miltiorrhiza Bge. promoting tight junction protein expression for therapeutic effects on lung cancer.

Salvia miltiorrhiza Bge. is a traditional Chinese medicine (TCM) that has been used for treatment of various diseases, including cancer by activating blood circulation and removing blood stasis. Tanshinone (TanIIA) and cryptotanshinone (CPT) are major lipophilic compounds extracted from the root of Salvia miltiorrhiza Bge., which are considered to be the effective compounds affecting the efficacy of the anti-tumor therapy of Salvia miltiorrhiza Bge. We have explored the mechanism of CPT and TanIIA exerting inhibition in non-small cell lung cancer (NSCLC) to provide experimental data support for guiding the translational development and clinical application of anti-tumor components of TCM. The subcutaneous tumor model and in vitro culture model of A549 cells was constructed to evaluate CPT and TanIIA's tumour-inhibitory effect respectively. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to CPT and TanIIA treatment. qRT-PCR and Western blot were used to explore the mechanism of CPT and TanIIA intervention on NSCLC. Both CPT and TanIIA significantly inhibited the proliferation of A549 tumor cells and tumor growth in animal models. After intervention, the migration ability decreased and the level of apoptosis increased. RNA-seq results showed that both CPT and TanIIA could cause gene differential expression, miR-21-5p as one of the most significant gene expression differences between the two groups, and could act on cell connectivity. CPT and TanIIA play a regulatory role in regulating tight junction proteins (Occludin and ZO1), and Occludin mRNA and protein levels were reduced in an in vitro miR-21-5p overexpression A549 cell model. The mechanisms may be related to the reduction of miR-21-5p expression to increase the level of promoted tight junction protein expression for the purpose of inhibiting proliferation and invasion of NSCLC.

A novel splice donor mutation in DCLRE1C caused atypical severe combined immunodeficiency in a patient with colon lymphoma: case report and literature review.

Introduction: Hypomorphic mutations of DCLRE1C cause an atypical severe combined immunodeficiency (SCID), and Epstein-Barr virus (EBV)-related colon lymphoma is a rare complication. Case presentation: A teenage boy presented with colon EBV-related colon lymphoma, plantar warts, and a history of recurrent pneumonia. His peripheral blood lymphocyte count and serum level of immunoglobulin (Ig) G were normal, but he exhibited a T+B-NK+ immunophenotype. Genetic analysis by whole exome sequencing revealed compound heterozygous mutations of DCLRE1C (NM_001033855.3), including a novel paternal splicing donor mutation (c.109 + 2T>C) in intron 1, and a maternal c.1147C>T (p.R383X) nonsense mutation in exon 13. Based on his clinical features and genetic results, the diagnosis of atypical SCID with colon lymphoma was established. Our review shows that seven patients, including our patient, have been reported to develop lymphoma, all with hypomorphic DCLRE1C mutations. Among these cases, six had EBV-related B-cell lineage lymphoma, and one had Hodgkin lymphoma with EBV reactivation. Unfortunately, all of the patients died. Conclusion: Recognizing the radiosensitivity of the disease is critical for the prognosis. Hematopoietic stem cell transplantation before being infected with EBV is an optimal treatment.

Publication trends and hotspots of colorectal adenoma during 2002-2022: a bibliometric and visualized analysis.

Background: Prevention and treatment of colorectal adenoma (CRA) are great significant to reduce morbidity and mortality of colorectal cancer. Although there have been numerous studies on CRA recently, few publications utilized the bibliometrics to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and frontier progress of CRA over the past 20 years. Methods: The Web of Science Core Collection was utilized to extracted all studies of CRA during 2002-2022. Bibliometric tools including CiteSpace, VOSviewer, and the Online Analysis Platform of Literature Metrology were used for statistical analysis. CiteSpace and the Online Analysis Platform were used to evaluate the contributions of various countries/regions, institutions, authors, and journals in this field. Research hotspots and trends were identified through keywords and references analysis by VOSviewer and CiteSpace. Results: 2,268 publications from 2002 to 2022 in total were identified. The number of global publications in this field has increased annually. The USA was the most productive country, contributing nearly 30% of global publications. But in recent years, China's publications grew rapidly and had the highest citation strength. The most productive institutions was the National Cancer Institute. Baron JA from the USA was the most productive and the one of most co-cited authors. Cancer Epidemiology Biomarkers & Prevention had the highest number of publications and Gastroenterology was the most co-cited journals. Analysis of keywords clusters showed that "mechanism/pathophysiology", "risk factors and prevention", "colonoscopy screening and treatment", "metabolism", and "microbiota" were the major frontier topics and the main research directions. Conclusions: CRA publications have shown a gradual upward trend in recent years, most of which have been published by developed countries. Developing countries should further focus on CRA research and transnational cooperation with developed countries in the future, in order to better improve the situation of the increasing morbidity and mortality of CRC. Baron JA was the most outstanding researcher in this field. More attention should be devoted to "pathogenesis of CRA", "less invasive diagnostic methods", "chemoprevention", and "screening and risk prediction of CRA including gut microbiome and metabolism", which will be frontiers in the future.

Downregulation of VPS13C promotes cisplatin resistance in cervical cancer by upregulating GSTP1.

Cisplatin resistance remains a major obstacle limiting the effectiveness of chemotherapy in cervical cancer. However, the underlying mechanism of cisplatin resistance is still unclear. In this study, we demonstrate that vacuolar protein sorting 13 homolog C (VPS13C) deficiency promotes cisplatin resistance in cervical cancer. Moreover, through an RNA sequencing screen, VPS13C deficiency was identified as negatively correlated with the high expression of glutathione S-transferase pi gene (GSTP1). Mechanistically, loss of VPS13C contributes to cisplatin resistance by influencing the expression of GSTP1 and inhibiting the downstream c-Jun N-terminal kinase (JNK) pathway. In addition, targeting GSTP1 with the inhibitor NBDHEX effectively rescued the cisplatin resistance induced by VPS13C deficiency. Overall, our findings provide insights into the underlying mechanisms of VPS13C in cisplatin resistance and identify VPS13C as a promising candidate for the treatment of chemoresistance in cervical cancer.

SETD8, a frequently mutated gene in cervical cancer, enhances cisplatin sensitivity by impairing DNA repair.

BACKGROUND: Cisplatin is commonly used to treat cervical cancer while drug resistance limits its effectiveness. There is an urgent need to identify strategies that increase cisplatin sensitivity and improve the outcomes of chemotherapy. RESULTS: We performed whole exome sequencing (WES) of 156 cervical cancer tissues to assess genomic features related to platinum-based chemoresistance. By using WES, we identified a frequently mutated locus SETD8 (7%), which was associated with drug sensitivity. Cell functional assays, in vivo xenografts tumor growth experiments, and survival analysis were used to investigate the functional significance and mechanism of chemosensitization after SETD8 downregulation. Knockdown of SETD8 increased the responsiveness of cervical cancer cells to cisplatin treatment. The mechanism is exerted by reduced binding of 53BP1 to DNA breaks and inhibition of the non-homologous end joining (NHEJ) repair pathway. In addition, SETD8 expression was positively correlated with resistance to cisplatin and negatively associated with the prognosis of cervical cancer patients. Further, UNC0379 as a small molecule inhibitor of SETD8 was found to enhance cisplatin sensitivity both in vitro and in vivo. CONCLUSIONS: SETD8 was a promising therapeutic target to ameliorate cisplatin resistance and improve the efficacy of chemotherapy.

Mitogenomes of Eight Nymphalidae Butterfly Species and Reconstructed Phylogeny of Nymphalidae (Nymphalidae: Lepidoptera).

The Nymphalidae family of cosmopolitan butterflies (Lepidoptera) comprises approximately 7200 species found on all continents and in all habitats. However, debate persists regarding the phylogenetic relationships within this family. In this study, we assembled and annotated eight mitogenomes of Nymphalidae, constituting the first report of complete mitogenomes for this family. Comparative analysis of 105 mitochondrial genomes revealed that the gene compositions and orders were identical to the ancestral insect mitogenome, except for Callerebia polyphemus trnV being before trnL and Limenitis homeyeri having two trnL genes. The results regarding length variation, AT bias, and codon usage were consistent with previous reports on butterfly mitogenomes. Our analysis indicated that the subfamilies Limenitinae, Nymphalinae, Apaturinae, Satyrinae, Charaxinae, Heliconiinae, and Danainae are monophyletic, while the subfamily the subfamily Cyrestinae is polyphyletic. Danainae is the base of the phylogenetic tree. At the tribe level, Euthaliini in Limenitinae; Melitaeini and Kallimini in Nymphalinae; Pseudergolini in Cyrestinae; Mycalesini, Coenonymphini, Ypthimini, Satyrini, and Melanitini in Satyrinae; and Charaxini in Charaxinae are regarded as monophyletic groups. However, the tribe Lethini in Satyrinae is paraphyletic, while the tribes Limenitini and Neptini in Limenitinae, Nymphalini and Hypolimni in Nymphalinae, and Danaini and Euploeini in Danainae are polyphyletic. This study is the first to report the gene features and phylogenetic relationships of the Nymphalidae family based on mitogenome analysis, providing a foundation for future studies of population genetics and phylogenetic relationships within this family.

A TMVP1-modified near-infrared nanoprobe: molecular imaging for tumor metastasis in sentinel lymph node and targeted enhanced photothermal therapy.

BACKGROUND: TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging. RESULTS: In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine. CONCLUSION: TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.

Two Birds with One Stone: Copper-Based Adsorbents Used for Photocatalytic Oxidation of Hg0 (Gas) after Removal of PH3.

CuX/TiO2 adsorbents with CuO as the active component were prepared via a simple impregnation method for efficient purification of phosphine (PH3) under the conditions of low temperatures (90 °C) and low oxygen concentration (1%). The PH3 breakthrough capacity of optimal adsorbent (Cu30/TiO2) is 136.2 mg(PH3)·gsorbent-1, and the excellent dephosphorization performance is mainly attributed to its abundant sur face-active oxygen and alkaline sites, large specific surface area, and strong interaction between CuO and the support TiO2. Surprisingly, CuO is converted to Cu3P after the dephosphorization by CuX/TiO2. Since Cu3P is a P-type semiconductor with high added value, the deactivated adsorbent (Cu3P/TiO2) is an efficient heterostructure photocatalyst for photocatalytic removal of Hg0 (gas) with the Hg0 removal performance of 92.64% under visible light. This study provides a feasible strategy for the efficient removal and resource conversion of PH3 under low-temperature conditions and the alleviation of the environmental risk of secondary pollution.

Effect of online aerobic exercise training in patients with bipolar depression: Protocol of a randomized clinical trial.

Introduction: Bipolar disorder (BD) is a common and debilitating mental illness that affects about 400 million people worldwide, decreasing their functionality and quality of life. Medication and psychotherapy are recommended for treatment of BD, while some evidence indicates that exercise could improve the clinical outcome of BD. This study aims to investigate whether exercise intervention could reduce the mood symptoms and inflammation level of BD. Methods: This is a longitudinal, interventional, randomized, and single-blind trial. We plan to recruit 94 patients diagnosed with BD in depression episode. Patients will be randomly assigned to treatment as usual + aerobic exercise group (intervention group) and treatment as usual (TAU) only group, at a ratio of 1:1. The intervention group will undergo 40-min aerobic exercise training twice a week for eight weeks. The primary outcome of this study is the mean change of Hamilton Depression Rating Scale 17 (HAMD 17) scores from baseline to week 8. The Young Manic Rating Scale (YMRS), Self-Rating Depression Scale (SDS), and Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) levels will also be measured. The measurements will be performed at baseline, immediately after intervention and two months after intervention. Discussion: Aerobic exercise training + treatment is expected to bring more benefits to BD patients than TAU only. This trial might provide stronger evidence of physical exercise efficacy for BD treatment. Clinical trial registration: This study was approved by the Chinese Clinical Trial Registry (Registration Code: ChiCTR2200057159). Registered on 1 March 2022.

Polydopamine-doped supramolecular chiral hydrogels for postoperative tumor recurrence inhibition and simultaneously enhanced wound repair.

Cancer recurrence remains a major challenge after primary tumor excision, and the inflammation of tumor-caused wounds can hinder wound healing and potentially promote tumor growth. Herein, a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel system encapsulated with polydopamine nanoparticles (PDA-NPs) has been developed in order to prevent tumor relapse after surgery and promote wound repair. PDA-NPs allow for near-infrared (NIR) light-triggered photothermal therapy, especially, it can scavenge free radicals in the surgical wound. LPFEG can mimic native extracellular matrix (ECM) structure to create a chiral microenvironment that enhances fibroblast adhesion, proliferation, and new tissue regeneration. With anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is significantly enhanced by the integration of chemo-photothermal therapy both in vitro and in vivo. The PDA-based chiral supramolecular composite hydrogel as an effective postoperative adjuvant possesses promising applicable prospects in inhibiting tumor recurrence and accelerating wound healing after operation. STATEMENT OF SIGNIFICANCE: After primary tumor excision, cancer recurrence remains a severe concern, and the inflammation induced by tumor-related wounds can delay wound healing. Herein, we designed a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel platform that was co-assembled with polydopamine nanoparticles (PDA-NPs). Among them, PDA-NPs can offer photothermal therapy and scavenge free radicals in surgical wounds. LPFEG can create a chiral microenvironment that promotes fibroblast adhesion, proliferation, and new tissue regeneration. Furthermore, with anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is considerably boosted. Therefore, the PDA-based chiral supramolecular hydrogel shows high application potential as a postoperative adjuvant in preventing tumor relapse as well as accelerating wound healing after surgery.

Efficacy and safety of Xuebijing injection for radiation pneumonitis: A meta-analysis.

BACKGROUND: Currently, the treatment of radiation pneumonitis (RP) remains a clinical challenge. Although glucocorticoids are used for RP treatment, they have associated side effects. Xuebijing injection (XBJ) has been widely used for RP treatment in China, but so far no meta-analysis has evaluated its efficacy and safety. METHODS: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, WANFANG database, SinoMED, and China Science and Technology J Database were searched for randomized controlled trials related to XBJ in RP treatment. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment. The outcomes were synthesized and analyzed using the Cochrane Review Manager (RevMan 5.3) software, and a forest plot generated. RESULT: Eight articles met the eligibility criteria for further data extraction and meta-analysis. A total of 578 patients with RP participated in these studies, including 296 in the experimental group (XBJ+BT), and 282 in the control group (BT). The results of the meta-analysis revealed that compared to the BT group, XBJ+BT significantly increased the total effective rate (n = 578; RR = 1.45, 95% CI: 1.30 to 1.61, p<0.0001), and IL-10 expression (n = 296; MD = 17.62, 95% CI:13.95 to 21.29, p<0.00001), decreased interleukin-6 (IL-6) expression (n = 296; MD = -21.56, 95% CI:-27.37 to -15.76, p<0.00001), that of tumor necrosis factor alpha (n = 246; MD = -25.63, 95% CI:-30.77 to -20.50, p<0.00001), and that of C-reactive protein (n = 296; MD = -48.61, 95% CI:-56.49-40.73, p< 0.00001). CONCLUSION: Based on our results, we do not recommend XBJ as an adjuvant treatment for RP. Further randomized controlled trials with rigorous design, strict implementation, and standard reporting are needed to further evaluate the efficacy and safety of XBJ for RP treatment. SYSTEMATIC REVIEW REGISTRATION: INPLASY registration number: INPLASY2020120037.

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy.

In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs, partly caused by the absence of tumor-infiltrating lymphocytes (TILs), significantly limits the application of ICIs. Converting these immune "cold" tumors into "hot" tumors that may respond to ICIs is an unsolved question in cancer immunotherapy. Since it is a general characteristic of cancers to resist apoptosis, induction of non-apoptotic regulated cell death (RCD) is emerging as a new cancer treatment strategy. Recently, several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses. Thus, targeted therapies (inducers or inhibitors) against autophagy, ferroptosis, pyroptosis, and necroptosis in combination with immunotherapy may exert potent antitumor activity, even in tumors resistant to ICIs. This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, pyroptosis, and necroptosis, and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.

The exon 12-containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway.

LIM homeobox 6 (LHX6) has been reported to be downregulated and inhibits cell proliferation in various cancers. Alternative splicing of LHX6 leads to six annotated isoforms, which can be found in the NCBI database. However, the expression patterns and potential roles of these isoforms remain poorly characterized in cervical cancer. Here, we demonstrated that the LHX6 isoforms containing exon 12 (LHX6EX(+12) group) and isoforms lacking exon 12 (LHX6EX(-12) group) were differentially expressed in cervical tissue by qRT-PCR. The mRNA expression level of LHX6EX(+12) group was higher than that of LHX6EX(-12) group in cervical cancer tissue. Knockdown of LHX6EX(+12) group and all LHX6 isoforms (LHX6All group) inhibited cell growth, increased cell apoptosis, and induced cell cycle arrest from G0/G1 phase to S phase in vitro. Consistently, overexpression of the LHX6EX(+12) group promoted cervical cancer cell proliferation in vitro. In contrast, no significant differences in cell proliferation were found between LHX6EX(-12) isoform knockdown group and its control. RNA-sequencing suggested that the LHX6EX(+12) isoform group might exert its cancer-promoting effects in cervical cancer via regulating MAPK signaling pathway. Downregulation of the LHX6EX(+12) group significantly suppressed the phosphorylation of MRK, ERK, JNK, and P38 at the protein level. We also identified some unique biological processes and signaling pathways in which each isoform group might be involved. In summary, our results indicated that LHX6EX(+12) isoform group was the dominant oncogenic type of LHX6 in cervical cancer, which may be a new biomarker and a potential precise therapeutic target for cervical cancer in the future.