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Background: Exposure to ultraviolet B (UVB) radiation can damage the epidermis barrier function and eventually result in skin dryness. At present, little work is being devoted to skin dryness. Searching for active ingredients that can protect the skin against UVB-induced dryness will have scientific significance.Methods:Saussurea involucrata polysaccharide (SIP) has been shown to have significant antioxidant and anti-photodamage effects on the skin following UVB irradiation. To evaluate the effect of SIP on UVB-induced skin dryness ex vivo, SIP-containing hydrogel was applied in a mouse model following exposure to UVB and the levels of histopathological changes, DNA damage, inflammation, keratinocyte differentiation, lipid content were then evaluated. The underlying mechanisms of SIP to protect the cells against UVB induced-dryness were determined in HaCaT cells.Results: SIP was found to lower UVB-induced oxidative stress and DNA damage while increasing keratinocyte differentiation and lipid production. Western blot analysis of UVB-irradiated skin tissue revealed a significant increase in peroxisome proliferator-activated receptor-α (PPAR-α) levels, indicating that the underlying mechanism may be related to PPAR-α signaling pathway activation.Conclusions: By activating the PPAR-α pathway, SIP could alleviate UVB-induced oxidative stress and inhibit the inflammatory response, regulate proliferation and differentiation of keratinocytes, and mitigate lipid synthesis disorder. These findings could provide candidate active ingredients with relatively clear mechanistic actions for the development of skin sunscreen moisturizers.

The integrity of skin tissue structure and function plays an important role in maintaining skin rejuvenation. Ultraviolet (UV) radiation is the main environmental factor that causes skin aging through photodamage of the skin tissue. Cryptotanshinone (CTS), an active ingredient mianly derived from the Salvia plants of Lamiaceae, has many pharmacological effects, such as anti-inflammatory, antioxidant, and anti-tumor effects. In this study, we showed that CTS could ameliorate the photodamage induced by UV radiation in epidermal keratinocytes (HaCaT) and dermal fibroblasts (HFF-1) when applied to the cells before exposure to the radiation, effectively delaying the aging of the cells. CTS exerted its antiaging effect by reducing the level of reactive oxygen species (ROS) in the cells, attenuating DNA damage, activating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and reduced mitochondrial dysfunction as well as inhibiting apoptosis. Further, CTS could promote mitochondrial biosynthesis in skin cells by activating the AMP-activated protein kinase (AMPK)/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) signaling pathway. These findings demonstrated the protective effects of CTS against UV radiation-induced skin photoaging and provided a theoretical and experimental basis for the application of CTS as an anti-photodamage and anti-aging agent for the skin.

Plastic recycling is an effective strategy to solve the shortage of national resources and improve the ecological environment. Herein, a novel approach was proposed to identify different colored plastics using laser-induced breakdown spectroscopy (LIBS) by neighborhood component analysis (NCA) and support vector machine (SVM). Six kinds of plastics (PVC, POM, ABS, PP, PA, and PE) with multiple colors were used to verify the feasibility of this method. Firstly, the types of plastics were classified by SVM, and the average accuracy about 97% was obtained. Then the same type of plastics with multiple colors was classified by SVM, and more than 99% average accuracy was acquired. However, the average accuracy of PVC by SVM was only 82%. To improve the average identification accuracy of PVC, the neighborhood component analysis (NCA) was used for feature selection by evaluating the weights of spectral lines. The spectral lines of focus elements (hydrogen (H), potassium (K), carbon (C), etc.) with higher weight were used as the input of SVM. The average accuracy of NCA-SVM was 91%, which higher than 9% and 5% with SVM and principal component analysis (PCA) combined with SVM (PCA -SVM), respectively. The results demonstrated that LIBS with the SVM and NCA-SVM can acquire high accuracy identification of different plastics, as well as recognition of the same type of plastics with different colors.

To solve the adulteration problem of brown rice flour in the commodity market, a novel, accurate, and stable detection method based on time-resolved laser-induced breakdown spectroscopy (TR-LIBS) is proposed. Qualitative and quantitative analysis was used to detect five adulterants and seven different adulterant ratios in brown rice flour. Being able to excavate more information from plasma by obtaining time-resolved spectra, TR-LIBS has a stronger performance, which has been further verified by experiments. For the qualitative analysis of adulterants, the traditional machine learning models based on TR-LIBS, linear discriminant analysis (LDA), naïve Bayes (NB) and support vector machine (SVM) have significantly better classification accuracy than those based on traditional LIBS, increasing by 3–11%. The deep learning classification model based on TR-LIBS also achieved the same results, with an accuracy increase of more than 8%. For the quantitative analysis of the adulteration ratio, compared with traditional LIBS, the quantitative model based on TR-LIBS reduces the limit of detection (LOD) of five adulterants from about 8–51% to 4–19%, which effectively improves the quantitative detection performance. Moreover, t-SNE visualization proved that there were more obvious boundaries between different types of samples based on TR-LIBS. These results demonstrate the great prospect of TR-LIBS in the identification of brown rice flour adulteration.

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

Objective: Exposure to ultraviolet B (UVB) can cause skin damage through oxidative stress, DNA damage, and apoptosis. Keratinocyte growth factor (KGF) has been shown to reduce the content of intracellular reactive oxygen species (ROS) following UVB exposure, a role that is crucial for the efficient photoprotection of skin. The present study evaluated the photoprotective effect of KGF-2 on UVB-induced skin damage and explored its potential molecular mechanism.Methods: To evaluate the effect of KGF-2 on UVB-induced damage ex vivo, a human epidermal full-thickness skin equivalent was pretreated without or with KGF-2 and then exposed to UVB and the levels of histopathological changes, DNA damage, inflammation, and apoptosis were then evaluated. The ability of KGF-2 to protect the cells against UVB-inflicted damage and its effect on ROS production, apoptosis, and mitochondrial dysfunction were determined in HaCaT cells.Results: Pretreatment of the epidermis with KGF-2 ameliorated the extent of photodamage. At the cellular level, KGF-2 could attenuate ROS production, apoptosis, DNA damage, and mitochondrial dysfunction caused by UVB exposure. KGF-2 could also activate the aryl hydrocarbon receptor (AhR) to trigger the Nrf2 signaling pathway.Conclusion: Taken together, our findings suggested that KGF-2 could ameliorate UVB-induced skin damage through inhibiting apoptosis, reducing oxidative stress, and preventing DNA damage and mitochondrial dysfunction via regulating AhR/Nrf2 signaling pathway.

Background: Macrophages can selectively recognize and eliminate senescent cells, but this function is impaired with age, resulting in excessive accumulation of senescent cells in the skin, which ultimately causes skin aging. Therefore, enhancing the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts from aging skin may be an effective skin rejuvenation strategy.Methods: In this study, a macrophage and senescent skin cell co-culture model was established whereby THP-1-derived macrophages and tert-butyl hydroxide-induced senescent skin cells (HaCaT and HFF-1) were grown in the same culture. Senescent skin cells were detected by the SPiDER-βgal assay, and the expression of secretory phenotype factors related to senescence was assayed by qPCR. The effect of carnosine on the number of SA-β-gal positive skin cells in the macrophage-senescent skin cell co-culture was evaluated and compared with that in the senescent skin cell monoculture.Results: Carnosine promoted macrophage-mediated elimination of senescent skin cells in the co-culture. Through the AKT2 signaling pathway, carnosine upregulated the expression of CD36 and receptors for advanced glycation end products and elevated the phagocytic capacity of the macrophages, thereby promoting the ability of the macrophages to eliminate the senescent skin cells.Conclusions: Carnosine could boost the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts in the macrophage-senescent skin cell co-culture by activating the AKT2 signaling pathway, suggesting the possibility of using carnosine as an agent to reverse skin aging.

BACKGROUND: Insufficient apoptosis in activated lymphocytes contributes to the development of autoimmune hepatitis (AIH). Baicalein (BE), a flavonoid originally isolated from the root of Scutellaria baicalensis Georgi, possesses anti-inflammatory properties. However, whether BE can selectively induce apoptosis in activated lymphocytes and exert therapeutic effect on AIH has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: The pro-apoptotic properties of BE were evaluated in vitro on different types of immune cells, and in vivo effects of BE were examined in a murine model of Concanavalin A (Con A)-induced hepatitis. In vitro treatment with BE resulted in a higher increase in the level of apoptosis in Con A-stimulated murine splenocytes, Con A-stimulated CD3(+) splenocytes, lipopolysaccharide (LPS)-stimulated CD19(+) splenocytes, and phorbol 12-myristate 13-acetate/ionomycin-stimulated Jurkat T cells, compared with that in unstimulated naïve ones. Murine bone marrow-derived dentritic cells, peritoneal macrophages, and RAW264.7 cells, either stimulated with LPS or unstimulated, were all insensitive to the BE-induced apoptosis. BE treatment also led to a loss of mitochondrial membrane potential, an increase of cytochrome c release from mitochondria to the cytosol, a decrease in the ratio of Bcl-2/Bax, and activation of caspase-9,-3 in Con A-stimulated CD3(+) splenocytes and LPS-stimulated CD19(+) splenocytes, while showing no impact on Fas/FasL expressions and caspase-8 activation. In vivo administration of BE alleviated Con A-induced liver injury, suppressed serum level of TNF-α and IFN-γ, and reduced liver infiltration of mononuclear cells (MNCs). Furthermore, BE treatment increased the incidences of apoptosis in liver-infiltrating MNCs and splenocytes, as well as in CD3(+) and CD19(+) splenocytes. When liver MNCs and splenocytes from BE-treated mice were cultured in vitro for 24 h, they exhibited marked increase in apoptosis compared to vehicle-treated control. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates the ability of BE to promote apoptosis in activated lymphocytes through mitochondrial pathway and its potential use in the treatment of AIH.

Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

This study was aimed to investigate the effects of baicalin (BA), a major flavonoid constituent found in the herb Baikal skullcap, on dendritic cells (DCs). DCs were generated by culturing murine bone marrow (BM) cells for 6 days with granulocyte–macrophage colony-stimulating factor and interleukin (IL)-4, and lipopolysaccharide (LPS) was added on day 5 to stimulate DCs maturation. The expression levels of DC maturity markers (CD80/CD86) were assessed by flow cytometry using direct immunofluorescence method. IL-12 levels in the culture supernatants were assayed by ELISA. Apoptosis of DCs was analyzed by flow cytometry after annexin V/propidium iodide staining. The mitochondrial membrane potential (Δψm) changes were measured by using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Exposure of DCs to BA (2–50 μM) during BM cell differentiation showed no effects on the up-regulation of CD80/CD86 expression on DCs in response to LPS stimulation, but reduced DCs recovery by inducing apoptosis, and significantly inhibited the release of IL-12 to culture supernatants. BA-induced DC apoptosis in a time- and dose-dependent way, and immature DCs were more sensitive for BA-induced apoptosis than mature DC. BA also induced Δψm changes in DCs. These results demonstrate that BA induces selective apoptosis in immature DCs possibly through mitochondria-mediated pathway.

This study investigates the impact of Saussurea involucrata polysaccharide on glucocorticoid-induced epidermal atrophy and barrier dysfunction. The topical application of Saussurea involucrata polysaccharide to the shaved dorsal skin of mice, administered 30 min after clobetasol propionate treatment twice daily for 6 d, significantly prevented clobetasol propionate-induced transepidermal water loss elevation and reduction in stratum corneum hydration. This was accompanied by an increase in epidermal thickness. Nile red staining demonstrated Saussurea involucrata polysaccharide augmentation of the overall epidermal lipid amount. Molecular analyses, including real-time quantitative polymerase chain reaction and immunohistochemical analysis, unveiled Saussurea involucrata polysaccharide influence on the upregulation of major lipidsynthesizing enzymes (serine-palmitoyl transferase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and fatty acid synthase) and epidermal differentiation-related proteins (filaggrin and involucrin). In conclusion, these findings suggest that Saussurea involucrata polysaccharide effectively prevents glucocorticoid-induced epidermal atrophy and barrier impairment by enhancing epidermal lipid synthesis and stimulating keratinocyte differentiation. [ABSTRACT FROM AUTHOR]

Abstract Vitamin A is a crucial nutrient renowned for its role in visual health and cellular regulation. Its derivatives influence cell differentiation, proliferation, and tissue homeostasis, making them significant in cancer research due to their effects on both normal and tumour cells. This review explores the intricate relationship between vitamin A metabolism and the extracellular matrix (ECM) in cancer. The ECM profoundly affects tumour behaviour, including proliferation, invasion, and metastasis. Alterations in the ECM can facilitate tumour progression, and vitamin A derivatives have shown potential in modulating these changes. Through transcriptional regulation, vitamin A impacts ECM components and matrix metalloproteinases, influencing tumour dynamics. The review highlights the potential of vitamin A and its derivatives as adjunctive agents in cancer therapy. Despite promising laboratory findings, their clinical application remains limited due to challenges in translating these effects into therapeutic outcomes. Future research should focus on the modulation of retinol metabolism within tumours and the development of targeted therapies to enhance treatment efficacy and improve patient prognosis.

Abstract LHPP, a novel, recognized tumor suppressor, exerts a critical influence on the regulation of tumor cell proliferation and survival by modulating various signaling pathways with its phosphatase activity. Here, we unveil a robust correlation between reduced LHPP expression and adverse prognosis in prostate cancer. We demonstrate that LHPP interacts with AKT, thereby dampening AKT phosphorylation and subsequently inhibiting ACSL4 phosphorylation at the T624 site. This interaction impedes phosphorylation-dependent ubiquitination, thwarting SKP2 from recognizing and binding to ACSL4 at the K621 site. As a result, ACSL4 is spared from lysosomal degradation, leading to its accumulation and the promotion of lipid peroxidation, and ferroptosis. Moreover, our findings reveal that Panobinostat, a potent histone-deacetylase inhibitor, intricately regulates LHPP expression at multiple levels through the inhibition of HDAC3. This complex modulation enhances the ferroptosis pathway, offering a novel mechanism for curtailing the growth of prostate tumors and highlighting its significant translational potential for clinical application.

Abstract Sharply increased reactive oxygen species (ROS) are thought to induce oxidative stress, damage cell structure and cause cell death; however, its role in prostate cancer remains unclear. Enzalutamide is a widely used anti-prostate cancer drug that antagonizes androgen binding with its receptor. Further exploration of the mechanism and potential application strategies of enzalutamide is crucial for the treatment of prostate cancer. Here, we confirmed PEX10 can be induced by ROS activators while reduce ROS level in prostate cancer cells, which weakened the anti-tumor effect of ROS activators. The androgen receptor (AR) can promote the expression of PEX10 by acting as an enhancer in cooperation with FOXA1. The anti-tumor drug enzalutamide inhibits PEX10 by inhibiting the function of AR, and synergize with ROS activators ML210 or RSL3 to produce a stronger anti-tumor effect, thereby sensitizing cells to ROS activators. This study reveals a previously unrecognized function of enzalutamide and AR by regulating PEX10 and suggests a new strategy of enzalutamide application in prostate cancer treatment.

Abstract Heat shock protein family B [small] member 6 (HSPB6), widely found in various muscles, has been recently identified as a tumor suppressor gene. However, its role in prostate cancer remains unexplored. Herein, we investigated the expression of HSPB6 in prostate cancer and its association with prognosis. Our findings revealed that HSPB6 downregulation in prostate cancer correlated with a poor prognosis. Moreover, we discovered that HSPB6 can be phosphorylated and activated by 8-Br-cGMP, leading to apoptosis in prostate cancer cells by activating Cofilin. Additionally, we demonstrated that knocking down E2F1 by quinidine administration enhances the transcriptional level of HSPB6. Furthermore, we evaluated the combination of quinidine and 8-Br-cGMP as a potential therapeutic strategy for prostate cancer. Our results revealed that the combined treatment was more effective than either treatment alone in inhibiting the growth of prostate cancer through the HSPB6 pathway, both in vitro and in vivo. Overall, our study provides compelling evidence that HSPB6 suppresses malignant behavior in prostate cancer by inducing apoptosis. The combination of quinidine and 8-Br-cGMP emerges as a promising approach for the treatment of prostate cancer.

The technologies such as data, information and intelligence are gradually applied to the power industry, and the power industry is gradually realizing digital transformation to meet the requirements of more reliable, stable, intelligent and safe power supply. UHV converter station is the heart of power grid equipment, which mainly ensures the conversion between AC and DC to ensure the stable operation of the power system. Facing the situation that the fault location is difficult and the loss is too large, this paper introduces the Digital Twin Technology(DTT), which completes the real-time mapping of the data state between the physical body and the virtual body of the converter station line through the digital modeling of the physical intelligent equipment. The recognition rate of CNN-BiGRU model for line fault and type reaches 99.78 % and 98.56 %. The CNN-BiGRU model has the highest recognition rate and the best effect in terms of the line recognition rate and the fault type recognition rate. The maximum Recall and Precision values of CNN-BiGRU model are 99.67 % and 97.96 %. The closer the F1 is to 1, the better the performance of the model is, and the value of CNN-BiGRU reaches 0. 94, which shows that the model has good performance.

Abstract Background Upper tract urothelial carcinoma (UTUC) is a rare disease, belonging to the same category of urothelial cancers as bladder cancer (BC). Despite sharing similar non-surgical treatment modalities, UTUC demonstrates a higher metastasis propensity than BC. Furthermore, although both cancers exhibit similar molecular disease emergence mechanisms, sequencing data reveals some differences. Our study investigates the transcriptomic distinctions between UTUC and BC, explores the causes behind UTUC's heightened metastatic tendency, constructs a model for UTUC metastasis and prognosis, and propose personalized treatment strategies for UTUC. Methods In our research, we utilized differential gene expression analysis, interaction networks, and Cox regression to explore the enhanced metastatic propensity of UTUC. We formulated and validated a prognostic risk model using diverse techniques, including cell co-culture, reverse transcription quantitative polymerase chain reaction (rt-qPCR), western blotting, and transwell experiments. Our methodological approach also involved survival analysis, risk model construction, and drug screening leveraging the databases of CTRPv2, PRISM and CMap. We used the Masson staining technique for histological assessments. All statistical evaluations were conducted using R software and GraphPad Prism 9, reinforcing the rigorous and comprehensive nature of our research approach. Results Screening through inflammatory fibrosis revealed a reduction of extracellular matrix and cell adhesion molecules regulated by proteoglycans in UTUC compared with BC, making UTUC more metastasis-prone. We demonstrated that SDC1, LUM, VEGFA, WNT7B, and TIMP3, are critical in promoting UTUC metastasis. A risk model based on these five molecules can effectively predict the risk of UTUC metastasis and disease-free survival time. Given UTUC's unique molecular mechanisms distinct from BC, we discovered that UTUC patients could better mitigate the issue of poor prognosis associated with UTUC's easy metastasis through tyrosine kinase inhibitors (TKIs) alongside the conventional gemcitabine and cisplatin chemotherapy regimen. Conclusions The poor prognosis of UTUC because of its high metastatic propensity is intimately tied to inflammatory fibrosis induced by the accumulation of reactive oxygen species. The biological model constructed using the five molecules SDC1, LUM, VEGFA, WNT7B, and TIMP3 can effectively predict patient prognosis. UTUC patients require specialized treatments in addition to conventional regimens, with TKIs exhibiting significant potential.

Abstract Background As a novel necrosis manner, ferroptosis has been increasingly reported to play a role in tumor progression and treatment, however, the specific mechanisms underlying its development in prostate cancer remain unclear. Growing evidence showed that peroxisome plays a key role in ferroptosis. Herein, we identified a novel mechanism for the involvement of ferroptosis in prostate cancer progression, which may provide a new strategy for clinical treatment of prostate cancer. Methods Label-Free Mass spectrometry was used to screen and identify candidate proteins after ferroptosis inducer-ML210 treatment. Immunohistochemistry was undertaken to explore the protein expression of AGPS in prostate cancer tissues compared with normal tissues. Co-immunoprecipitation and GST pull-down were used to identify the directly binding of AGPS to MDM2 in vivo and in vitro. CCK8 assay and colony formation assay were used to illustrate the key role of AGPS in the progression of prostate cancer in vitro. The xenograft model was established to verify the key role of AGPS in the progression of prostate cancer in vivo. Results AGPS protein expression was downregulated in prostate cancer tissues compared with normal tissues from the first affiliated hospital of Zhengzhou University dataset. Lower expression was correlated with poorer overall survival of patients compared to those with high expression of AGPS. In addition, AGPS can promote ferroptosis by modulating the function of peroxisome-resulting in the lower survival of prostate cancer cells. Furthermore, it was shown that AGPS can be ubiquitinated and degraded by the E3 ligase-MDM2 through the proteasomal pathway. Meanwhile, kinase TrkA can promote the combination of AGPS and MDM2 by phosphorylating AGPS at Y451 site. It was verified that kinase TrkA inhibitor—Larotrectinib can increase the susceptibility of prostate cancer cells to ferroptosis, which leads to the inhibition of prostate cancer proliferation to a great extent in vitro and in vivo. Conclusion Based on these findings, we proposed the combination of ferroptosis inducer and TrkA inhibitor to synergistically exert anti-tumor effects, which may provide a new strategy for the clinical treatment of prostate cancer.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial–mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Urinary tumors primarily consist of kidney, urothelial, and prostate malignancies, which pose significant treatment challenges, particularly in advanced stages. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach, combining monoclonal antibody specificity with cytotoxic chemotherapeutic payloads. This review highlights recent advancements, opportunities, and challenges in ADC application for urinary tumors. We discuss the FDA-approved ADCs and other novel ADCs under investigation, emphasizing their potential to improve patient outcomes. Furthermore, we explore strategies to address challenges, such as toxicity management, predictive biomarker identification, and resistance mechanisms. Additionally, we examine the integration of ADCs with other treatment modalities, including immune checkpoint inhibitors, targeted therapies, and radiation therapy. By addressing these challenges and exploring innovative approaches, the development of ADCs may significantly enhance therapeutic options and outcomes for patients with advanced urinary tumor.

The formation and development of tubers, the primary edible and economic organ of potatoes, directly affect their yield and quality. The regulatory network and mechanism of tuberization have been preliminarily revealed in recent years, but plenty of relevant genes remain to be discovered. A few candidate genes were provided due to the simplicity of sampling and result analysis of previous transcriptomes related to tuberization. We sequenced and thoroughly analyzed the transcriptomes of thirteen tissues from potato plants at the tuber proliferation phase to provide more reference information and gene resources. Among them, eight tissues were stolons and tubers at different developmental stages, which we focused on. Five critical periods of tuberization were selected to perform an analysis of differentially expressed genes (DEGs), according to the results of the tissue correlation. Compared with the unswollen stolons (Sto), 2751, 4897, 6635, and 9700 DEGs were detected in the slightly swollen stolons (Sto1), swollen stolons (Sto2), tubers of proliferation stage 1 (Tu1), and tubers of proliferation stage 4 (Tu4). A total of 854 transcription factors and 164 hormone pathway genes were identified in the DEGs. Furthermore, three co-expression networks associated with Sto–Sto1, Sto2–Tu1, and tubers of proliferation stages two to five (Tu2–Tu5) were built using the weighted gene co-expression network analysis (WGCNA). Thirty hub genes (HGs) and 30 hub transcription factors (HTFs) were screened and focalized in these networks. We found that five HGs were reported to regulate tuberization, and most of the remaining HGs and HTFs co-expressed with them. The orthologs of these HGs and HTFs were reported to regulate processes (e.g., flowering, cell division, hormone synthesis, metabolism and signal transduction, sucrose transport, and starch synthesis) that were also required for tuberization. Such results further support their potential to control tuberization. Our study provides insights and countless candidate genes of the regulatory network of tuberization, laying the foundation for further elucidating the genetic basis of tuber development.

Abstract Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations of AOC1 and its regulatory mechanism in prostate cancer. Here, we reveal a novel action of AOC1 and a tumor suppressor mechanism in prostate cancer. AOC1 is downregulated in prostate cancer. Abatement of AOC1 in prostate cancer tissue is positively correlated with the tumor size, lymph node metastasis, and Gleason score for prostate cancer. Conversely, high expression of AOC1 is significantly associated with reduced proliferation and migration in prostate cancer both in vitro and in vivo. We show that the anticancer effect of AOC1 is mediated by its action on spermidine which leads to the activation of reactive oxygen species and ferroptosis. AOC1 expression in prostate cancer is positively regulated by the transcription factor SOX15. Therefore, SOX15 can transcriptionally promote AOC1 expression and strengthen this effect. Targeting AOC1 and SOX15 may be promising for the treatment of prostate cancer.

The uncertainty caused by the growing use of renewable energy sources, such as wind and solar energy, makes it difficult to forecast the operation costs of micro-energy systems, particularly those in remote rural areas. Motivated by this point, this paper analyzes the possible operational risks and then introduces Condition Value at Risk (CVaR) to quantify the cost of the operational risk. On this basis, stochastic programming based on a multi-energy microgrid planning model that minimizes the investment cost, the operating cost, and the cost of operational risk, while considering the physical limitations of the multi-energy microgrid, is presented. Especially, scenarios of wind and solar energy output are generated using the Latin hypercube sampling method and reduced using the crowding measure-based scenario reduction method. After piecewise linearization and second-order cone relaxation, the model proposed in this paper is processed as a mixed integer linear model and solved by CPLEX. According to the achieved typical scenarios processed by the reduction method, the simulation shows that the presented configuration model can balance the investment cost and the cost of the operational risk, which effectively enhances the system’s ability to cope with uncertainties and fluctuations. Moreover, by adjusting the risk preference coefficient, the conservativeness of the planning scheme can be correspondingly adjusted.

With the unprecedented development of green and renewable energy sources, the proportion of clean hydrogen (H2) applications grows rapidly. Since H2 has physicochemical properties of being highly permeable and combustible, high-performance H2 sensors to detect and monitor hydrogen concentration are essential. This review discusses a variety of fiber-optic-based H2 sensor technologies since the year 1984, including: interferometer technology, fiber grating technology, surface plasma resonance (SPR) technology, micro lens technology, evanescent field technology, integrated optical waveguide technology, direct transmission/reflection detection technology, etc. These technologies have been evolving from simply pursuing high sensitivity and low detection limits (LDL) to focusing on multiple performance parameters to match various application demands, such as: high temperature resistance, fast response speed, fast recovery speed, large concentration range, low cross sensitivity, excellent long-term stability, etc. On the basis of palladium (Pd)-sensitive material, alloy metals, catalysts, or nanoparticles are proposed to improve the performance of fiber-optic-based H2 sensors, including gold (Au), silver (Ag), platinum (Pt), zinc oxide (ZnO), titanium oxide (TiO2), tungsten oxide (WO3), Mg70Ti30, polydimethylsiloxane (PDMS), graphene oxide (GO), etc. Various microstructure processes of the side and end of optical fiber H2 sensors are also discussed in this review.