Achilles' heel of male infertility: good LEGO players.

In a recent journal article, Chen et al. identified a germ cell-specific cofactor, STYXL1, associated with male fertility function. Deletion of STYXL1 prevents the LEGO player CCT complex from properly folding key microtubule proteins of the sperm flagellum, which affects sperm motility and male fertility function.

Defect-Rich Single Atom Catalyst Enhanced Polysulfide Conversion Kinetics to Upgrade Performance of Li-S Batteries.

Lithium-sulfur (Li-S) batteries have attracted considerable attention owing to their extremely high energy densities. However, the application of Li-S batteries has been limited by low sulfur utilization, poor cycle stability, and low rate capability. Accelerating the rapid transformation of polysulfides is an effective approach for addressing these obstacles. In this study, a defect-rich single-atom catalytic material (Fe-N4/DCS) is designed. The abundantly defective environment is favorable for the uniform dispersion and stable existence of single-atom Fe, which not only improves the utilization of single-atom Fe but also efficiently adsorbs polysulfides and catalyzes the rapid transformation of polysulfides. To fully exploit the catalytic activity, catalytic materials are used to modify the routine separator (Fe-N4 /DCS/PP). Density functional theory and in situ Raman spectroscopy are used to demonstrate that Fe-N4 /DCS can effectively inhibit the shuttling of polysulfides and accelerate the redox reaction. Consequently, the Li-S battery with the modified separator achieves an ultralong cycle life (a capacity decay rate of only 0.03% per cycle at a current of 2 C after 800 cycles), and an excellent rate capability (894 mAh g-1 at 3 C). Even at a high sulfur loading of 5.51 mg cm-2 at 0.2 C, the reversible areal capacity still reaches 5.4 mAh cm-2 .

Clinical effect of micturition interruption exercise on urinary incontinence after radical prostatectomy.

PURPOSE: To explore the effectiveness of micturition interruption exercise in improving the incidence of urinary incontinence after radical prostatectomy. MATERIALS AND METHODS: With a retrospective case-control study, 96 patients admitted in the Second Affiliated Hospital of Zhejiang Chinese Medical University from August 2014 to August 2020 and underwent radical prostatectomy were collected as the subjects. Those patients who used micturition interruption exercise (n = 48) were set as the therapy group, and the control group was collected according to the ratio of 1:1; the patients used Kegel exercise (n = 48) to compare the rehabilitation of urinary incontinence in patients and the effect of training compliance on rehabilitation. RESULTS: The recovery time of urinary incontinence in the therapy group was significantly shorter than that of the control group. In the therapy group, 83.3% of patients with training compliance reached an average or above, while the control group only accounted for 58.3%. International Consultation on Incontinence Questionnaire Short-Form score of the therapy group was lower than that of the control group after surgery. Spearman analysis suggests that there is a negative correlation between the postoperative urinary incontinence recovery time and compliance with the micturition interruption exercise. CONCLUSIONS: Micturition interruption exercise could not only improve the compliance of patients with exercise, but also significantly shorten the recovery time of urinary incontinence after radical prostatectomy.

Response mechanism of Chlamydomonas reinhardtii to nanoscale bismuth oxyiodide (nano-BiOI): Integrating analysis of mineral nutrient metabolism and metabolomics.

Nanoscale bismuth oxyiodide (nano-BiOI) is widely studied and applied in environmental applications and biomedical fields, with the consequence that it may be deposited into aquatic environments. However, the impact of nano-BiOI on aquatic ecosystems, especially freshwater microalga, remains limited. Herein, the nano-BiOI was synthesized and its response mechanism towards microalga Chlamydomonas reinhardtii was evaluated. Results showed that a low concentration of nano-BiOI (5 mg/L) could stimulate algal growth at the early stage of stress. With the increase in concentration, the growth rate of algal cells was inhibited and showed a dose effect. Intracellular reactive oxygen species (ROS) were significantly induced and accompanied by enhanced lipid peroxidation, decreased nonspecific esterase activity, and significantly upregulated glutathione S-transferase activity (GST) activity. Mineral nutrient metabolism analysis showed that nano-BiOI significantly interfered with the mineral nutrients of the algae. Non-targeted metabolomics identified 35 different metabolites (DEMs, 22 upregulated, and 13 downregulated) under 100 mg/L BiOI stress. Metabolic pathway analysis demonstrated that a high concentration of nano-BiOI significantly induced metabolic pathways related to amino acid biosynthesis, lipid biosynthesis, and glutathione biosynthesis, and significantly inhibited the sterol biosynthesis pathway. This finding will contribute to understanding the toxicological mechanisms of nano-BiOI on C. reinhardtii.

Cascade Reaction of 2-Naphthols and Azirines: One-Pot Synthesis of C-3 Naphthol-Substituted Benzo[e]indoles.

A copper-catalyzed annulation of 3-aryl-2H-azirines with 2-naphthols has been developed for the rapid assembly of C-3-naphthol-substituted benzo[e]indoles in one pot. This cascade reaction was realized through dearomatic nucleophilic ring opening of azirine, intramolecular cyclization, and oxidative cross-dehydrogenative coupling to furnish the important unreported π-expanded naphthol/benzo[e]indole biaryls.

[Prostatic fibrosis: Progress in studies].

The prostate volume is not enlarged in some patients with lower urinary tract symptoms (LUTS). Evidence shows that prostate fibrosis, in addition to BPH and smooth muscle dysfunction, is one of the causes of LUTS, and that its occurrence is related to inflammation of various causes, ischemia, hypoxia and drugs, with the differentiation, aggregation and activation of myofibroblasts involved in its pathogenesis. Therefore, anti-inflammation and anti-fibrosis strategies may be considered as potential targets for the treatment of LUTS. This article presents an overview on the causes of prostatic fibrosis, its diagnosis, its association with LUTS, and the advances in its treatment.

Fibroblast growth factor 16 stimulates proliferation but blocks differentiation of rat stem Leydig cells during regeneration.

OBJECTIVES: We aim to investigate the effects of fibroblast growth factor 16 (FGF16) on Leydig cell regeneration in ethane dimethane sulphonate (EDS)-treated rat testis. METHODS: We intraperitoneally inject 75 mg/kg EDS to adult male Sprague Dawley rats and then intratesticularly inject FGF16 (0, 10 and 100 ng/testis/day) from post-EDS day 14 for 14 days. We investigate serum hormone levels, Leydig cell number, gene and protein expression in vivo. We also explore the effects of FGF16 treatment on stem Leydig cell proliferation in vitro. RESULTS: FGF16 lowers serum testosterone levels (21.6% of the control at a dose of 100 ng/testis) without affecting the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) on post-EDS day 28 in vivo. FGF16 increases Leydig cell number at doses of 10 and 100 ng/mg without affecting Sertoli cell number, increases the percentage of PCNA-positive Leydig cells, and down-regulates the expression of Leydig cell genes (Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1 and Hsd17b3) and Sertoli cell genes (Fshr, Dhh and Sox9) and their proteins in vivo. FGF16 increases phosphorylation of AKT1 and AKT2 as well as EKR1/2 in vivo, indicating that it possibly acts via AKT1/ATK2 and ERK1/2 pathways. FGF16 also lowers medium testosterone levels and down-regulates the expression of Leydig cell genes (Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1 and Hsd17b3) but increases EdU incorporation into stem Leydig cells in vitro. CONCLUSIONS: These data suggest that FGF16 stimulates stem and progenitor Leydig cell proliferation but blocks their differentiation, thus lowering testosterone biosynthesis.

Induced pluripotent stem cell-derived conditional medium promotes Leydig cell anti-apoptosis and proliferation via autophagy and Wnt/ß-catenin pathway.

Leydig cell transplantation is a better alternative in the treatment of androgen-deficient males. The main purpose of this study was to investigate the effects of induced pluripotent stem cell-derived conditioned medium (iPS-CM) on the anti-apoptosis, proliferation and function of immature Leydig cells (ILCs), and illuminate the underlying mechanisms. ILCs were exposed to 200 µmol/L hydrogen peroxide (H2 O2 ) for 24 hours with or without iPS-CM treatments. Cell apoptosis was detected by flow cytometric analysis. Cell proliferation was assessed using cell cycle assays and EdU staining. The steroidogenic enzyme expressions were quantified with Western blotting. The results showed that iPS-CM significantly reduced H2 O2 -induced ILC apoptosis through down-regulation of autophagic and apoptotic proteins LC3-I/II, Beclin-1, P62, P53 and BAX as well as up-regulation of BCL-2, which could be inhibited by LY294002 (25 µmol/L). iPS-CM could also promote ILC proliferation through up-regulation of ß-catenin and its target proteins cyclin D1, c-Myc and survivin, but was inhibited by XAV939 (10 µmol/L). The level of bFGF in iPS-CM was higher than that of DMEM-LG. Exogenous bFGF (20 ng/mL) or Wnt signalling agonist lithium chloride (LiCl) (20 mmol/L) added into DMEM-LG could achieve the similar effects of iPS-CM. Meanwhile, iPS-CM could improve the medium testosterone levels and up-regulation of LHCGR, SCARB1, STAR, CYP11A1, HSD3B1, CYP17A1, HSD17B3 and SF-1 in H2 O2 -induced ILCs. In conclusion, iPS-CM could reduce H2 O2 -induced ILC apoptosis through the activation of autophagy, promote proliferation through up-regulation of Wnt/ß-catenin pathway and enhance testosterone production through increasing steroidogenic enzyme expressions, which might be used in regenerative medicine for future.

Dual functional NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ core-shell nanoparticles for cell temperature sensing and imaging.

Lanthanide-doped up-conversion nanoparticles (UCNPs) provide a remote temperature sensing approach to monitoring biological microenvironments. In this research, the UCNPs of NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ with hexagonal (ß)-phase were synthesized and applied in cell temperature sensing as well as imaging after surface modification with meso-2, 3-dimercaptosuccinic acid. In the core-shell UCNPs, Yb3+ ions were introduced as energy transfer media between sensitizers of Nd3+ and activators of Er3+ to improve Er3+emission and prevent their quenching behavior due to multiple energy levels of Nd3+. Under the excitations of 808 nm and 980 nm lasers, the NaYF4:Yb3+, Er3+@NaYF4:Yb3+, Nd3+ nanoparticles exhibited an efficient green band with two emission peaks at 525 nm and 545 nm, respectively, which originated from the transitions of 2H11/2 â†’ 4I15/2 and 4S3/2 â†’ 4I15/2 for Er3+ ions. We demonstrate that an occurrence of good logarithmic linearity exists between the intensity ratio of these two emission peaks and the reciprocal of the inside or outside temperature of NIH-3T3 cells. A better thermal stability is proved through temperature-dependent spectra with a heating-cooling cycle. The obtained viability of NIH-3T3 cells is greater than 90% after incubations of about 12 and 24 (h), and they possess a lower cytotoxicity of UCNPs. This work provides a method for monitoring the cell temperature and its living state from multiple dimensions including temperature response, cell images and visual up-conversion fluorescent color.

Heat shock protein 70 enhances mucosal immunity against human norovirus when coexpressed from a vesicular stomatitis virus vector.

UNLABELLED: Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide. Currently, there is no vaccine available to combat human NoV as it is not cultivable and lacks a small-animal model. Recently, we demonstrated that recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942-2952, 2011). To further improve the safety and efficacy of the vaccine candidate, heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A second construct was generated in which the firefly luciferase (Luc) gene was inserted in place of HSP70 as a control for the double insertion. The resultant recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more attenuated in cell culture and viral spread in mice than rVSV-VP1. At the inoculation dose of 1.0 × 10(6) PFU, rVSV-HSP70-VP1 triggered significantly higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA responses than rVSV-Luc-VP1, although serum IgG and T cell responses were similar. At the inoculation dose of 5.0 × 10(6) PFU, rVSV-HSP70-VP1 stimulated significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1. Fecal and vaginal IgA responses were also significantly increased when combined vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV-VP1 backbone further attenuates the VSV-based vaccine in vitro and in vivo, thus improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV vaccine. IMPORTANCE: Human norovirus (NoV) is responsible for more than 95% of acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for this virus. Development of a live attenuated vaccine for human NoV has not been possible because it is uncultivable. Thus, a live vector-based vaccine may provide an alternative vaccine strategy. In this study, we developed a vesicular stomatitis virus (VSV)-based human NoV vaccine candidate. We constructed rVSV-HSP70-VP1, coexpressing heat shock protein (HSP70) and capsid (VP1) genes of human NoV, and rVSV-Luc-VP1, coexpressing firefly luciferase (Luc) and VP1 genes. We found that VSVs with a double gene insertion were significantly more attenuated than VSV with a single VP1 insertion (rVSV-VP1). Furthermore, we found that coexpression or coadministration of HSP70 from VSV vector significantly enhanced human NoV-specific mucosal immunity. Collectively, we developed an improved live vectored vaccine candidate for human NoV which will be useful for future clinical studies.

Dynamic Changes in Qidan Aroma during Roasting: Characterization of Aroma Compounds and Their Kinetic Fitting.

Qidan is one of the most famous varieties of Wuyi Rock tea and has a strong aroma. The aroma-active compounds in Qidan subject to different roasting times were analyzed using solid-phase microextraction two-dimensional gas chromatography-olfactometry-mass spectrometry (SPME-GC×GC-O-MS), and a total of 92 aroma-active compounds were detected. Multivariate statistical analysis showed that the roasting time had a significant effect on the aroma characteristics of Qidan, and that the key products in the Maillard reaction accumulated with the extension of the roasting time; these key products were screened out according to the calculation of the odor activity values (OAVs), from which kinetic equations were established. It was found that the levels of 2-methylbutanal, 3-methylbutanal, 2-methylpyrazine, 2-ethyl-5-methylpyrazine, and benzaldehyde increased with time, while the contents of benzeneacetaldehyde showed a tendency to first increase and then decrease. This study provides a theoretical basis for flavor quality control during Qidan processing.

Rational Design of a Surface Acoustic Wave Device for Wearable Body Temperature Monitoring.

Continuous monitoring of vital signs based on advanced sensing technologies has attracted extensive attention due to the ravages of COVID-19. A maintenance-free and low-cost passive wireless sensing system based on surface acoustic wave (SAW) device can be used to continuously monitor temperature. However, the current SAW-based passive sensing system is mostly designed at a low frequency around 433 MHz, which leads to the relatively large size of SAW devices and antenna, hindering their application in wearable devices. In this paper, SAW devices with a resonant frequency distributed in the 870 MHz to 960 MHz range are rationally designed and fabricated. Based on the finite-element method (FEM) and coupling-of-modes (COM) model, the device parameters, including interdigital transducer (IDT) pairs, aperture size, and reflector pairs, are systematically optimized, and the theoretical and experimental results show high consistency. Finally, SAW temperature sensors with a quality factor greater than 2200 are obtained for real-time temperature monitoring ranging from 20 to 50 °C. Benefitting from the higher operating frequency, the size of the sensing system can be reduced for human body temperature monitoring, showing its potential to be used as a wearable monitoring device in the future.

Therapeutic strategies and predictive models for Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma in adults based on data of two Chinese medical centers.

OBJECTIVE: This study aims to establish an effective predictive model for predicting Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma (TFE3-RCC) and develop optimal therapeutic strategies. METHODS: Data from 4961 patients diagnosed with renal cell carcinoma at two medical centers in China were retrospectively analyzed. A cohort of 1571 patients from Zhejiang Provincial People's Hospital (Ra cohort) was selected to construct the model. Another cohort of 1124 patients from the Second Affiliated Hospital of Zhejiang Chinese Medical University was used for external validation (the Ha cohort). All patients with TFE3-RCC in both cohorts were included in the Ta cohort for the prognostic analysis. Univariate and multivariate binary logistic regression analyses were performed to identify independent predictors of the predictive nomogram. The apparent performance of the model was validated. Decision curve analysis was also performed to assess the clinical utility of the developed model. Factors associated with progression and prognosis in the Ta cohort were analyzed using the log-rank method, and Cox regression analysis and Kaplan-Meier survival curves were used to describe the effects of factors on prognosis and progression. RESULTS: Univariate and multivariate logistic regression analyses demonstrated that age, sex, BMI, smoking, eosinophils, and LDL were independent predictors of TFE3-RCC. Therefore, a predictive nomogram for TFE3-RCC, which had good discriminatory power (AUC = 0.796), was constructed. External validation (AUC = 0.806) also revealed good predictive ability. The calibration curves displayed good consistency between the predicted and observed incidences of TFE3-RCC. Invasion of regional lymph nodes, tyrosine kinase inhibitors, and surgical methods were independent factors associated with progression. Tyrosine kinase inhibitors are independent prognostic factors. CONCLUSION: This study not only proposed a high-precision clinical prediction model composed of various variables for the early diagnosis of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma but also optimized therapeutic strategies through prognostic analysis.

gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity.

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one ß-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 ß-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many ß-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

One new species of the genus Capnogryllacris Karny, 1937 (Orthoptera: Gryllacrididae) from China.

The paper reports a new species of the genus Capnogryllacris Karny, 1937 (Orthoptera: Gryllacrididae) from China, i.e. Capnogryllacris latilamargis sp. nov. The all specimens are deposited in the Museum of Hebei University, Baoding, China.

Two new species of the genus Ocellarnaca Gorochov, 2004 (Orthoptera: Gryllacrididae) from China.

The paper reports two new species of the genus Ocellarnaca Gorochov, 2004 (Orthoptera: Gryllacrididae) from China, i.e. Ocellarnaca longiprotubera sp. nov. and Ocellarnaca grossa sp. nov. The type specimens are deposited in the Museum of Hebei University, Baoding 071002, China.

MutexMatch: Semi-Supervised Learning With Mutex-Based Consistency Regularization.

The core issue in semi-supervised learning (SSL) lies in how to effectively leverage unlabeled data, whereas most existing methods tend to put a great emphasis on the utilization of high-confidence samples yet seldom fully explore the usage of low-confidence samples. In this article, we aim to utilize low-confidence samples in a novel way with our proposed mutex-based consistency regularization, namely MutexMatch. Specifically, the high-confidence samples are required to exactly predict "what it is" by the conventional true-positive classifier (TPC), while low-confidence samples are employed to achieve a simpler goal-to predict with ease "what it is not" by the true-negative classifier (TNC). In this sense, we not only mitigate the pseudo-labeling errors but also make full use of the low-confidence unlabeled data by the consistency of dissimilarity degree. MutexMatch achieves superior performance on multiple benchmark datasets, i.e., Canadian Institute for Advanced Research (CIFAR)-10, CIFAR-100, street view house numbers (SVHN), self-taught learning 10 (STL-10), and mini-ImageNet. More importantly, our method further shows superiority when the amount of labeled data is scarce, e.g., 92.23% accuracy with only 20 labeled data on CIFAR-10. Code has been released at https://github.com/NJUyued/MutexMatch4SSL.

Trilobatin, an Active Dihydrochalcone from Lithocarpus polystachyus, Prevents Cisplatin-Induced Nephrotoxicity via Mitogen-Activated Protein Kinase Pathway-Mediated Apoptosis in Mice.

Although naturally occurring flavonoids have shown beneficial effects on the side effects caused by cisplatin, there are few reports on the protective effect of dihydrochalcone on the cisplatin-induced toxicity. Trilobatin (TLB), as the major sweetener and active ingredient in Lithocarpus polystachyus Rehd, is a dihydrochalcone-like compound that can be present in concentrations of up to 10% or more in tender leaves. Herein, a cisplatin-induced acute kidney injury (AKI) model was established to investigate the protective effect and mechanism of TLB against the cisplatin-induced nephrotoxicity in mice. The results showed that TLB significantly reversed the inhibition of CRE, BUN, and MDA levels compared with the cisplatin group. Furthermore, TLB treatment (50 and 100 mg/kg) for 10 days significantly alleviated cisplatin-induced renal pathological changes. TUNEL staining showed that TLB administration can effectively improve the occurrence of apoptosis of renal tissue cells caused by cisplatin exposure. Importantly, western blot analysis verified that TLB alleviated cisplatin-induced nephrotoxicity by regulating the AKT/MAPK signaling pathway and apoptosis. In summary, our findings showed clearly that TLB has a significant preventive effect on cisplatin-induced AKI.

Medical image segmentation and reconstruction of prostate tumor based on 3D AlexNet.

BACKGROUND: Prostate cancer is a disease with a high incidence of tumors in men. Due to the long incubation time and insidious condition, early diagnosis is difficult; especially imaging diagnosis is more difficult. In actual clinical practice, the method of manual segmentation by medical experts is mainly used, which is time-consuming and labor-intensive and relies heavily on the experience and ability of medical experts. The rapid, accurate and repeatable segmentation of the prostate area is still a challenging problem. It is important to explore the automated segmentation of prostate images based on the 3D AlexNet network. METHOD: Taking the medical image of prostate cancer as the entry point, the three-dimensional data is introduced into the deep learning convolutional neural network. This paper proposes a 3D AlexNet method for the automatic segmentation of prostate cancer magnetic resonance images, and the general network ResNet 50, Inception -V4 compares network performance. RESULTS: Based on the training samples of magnetic resonance images of 500 prostate cancer patients, a set of 3D AlexNet with simple structure and excellent performance was established through adaptive improvement on the basis of classic AlexNet. The accuracy rate was as high as 0.921, the specificity was 0.896, and the sensitivity It is 0.902 and the area under the receiver operating characteristic curve (AUC) is 0.964. The Mean Absolute Distance (MAD) between the segmentation result and the medical expert's gold standard is 0.356 mm, and the Hausdorff distance (HD) is 1.024 mm, the Dice similarity coefficient is 0.9768. CONCLUSION: The improved 3D AlexNet can automatically complete the structured segmentation of prostate magnetic resonance images. Compared with traditional segmentation methods and depth segmentation methods, the performance of the 3D AlexNet network is superior in terms of training time and parameter amount, or network performance evaluation. Compared with the algorithm, it proves the effectiveness of this method.

Immune Modulator and Low-Temperature PTT-Induced Synergistic Immunotherapy for Cancer Treatment.

Immunotherapy has shown great potential in cancer therapeutics but has limitations of the insufficient activation of dendritic cells (DCs) and immune-suppressive microenvironment. To overcome these obstacles, a cascade synergistic immunotherapy nanosystem (denoted as CpG@PDA-FA) was designed to elevate anticancer immune response. The combination nanosystem including a photothermal agent polydopamine (PDA) and immunomodulator CpG oligodeoxynucleotides (CpG ODNs). On the one hand, polydopamine (PDA) acts as a photothermal agent to induce low-temperature PTT. It leads to immunogenic cell death (ICD), a programmed cell death pathway, which can activate DCs and enhance the antitumor immune response of T cells. On the other hand, CpG ODNs further promote maturation and migration of DCs as well as ameliorates the immunosuppression microenvironment of the tumor (TME). This paper focuses on a cancer synergistic treatment of ICD-induced immunotherapy by low-temperature PTT and ameliorates TME by immunomodulator CpG ODNs. We proved that CpG@PDA-FA NPs realized a remarkable synergistic treatment effect compared with respective single PTT or CpG therapy in the maturation of DCs and activation of T cells. In addition, CpG@PDA-FA NPs also reduced myeloid-derived suppressor cells and regulatory T cells to relieve immunosuppression. Hence, CpG@PDA-FA NPs provide a bidirectional immunotherapy strategy for tumor inhibition and highlight the cascade effects of low-temperature PTT and immunotherapy.