Evaluating the therapeutic potential of moxibustion on polycystic ovary syndrome: a rat model study on gut microbiota and metabolite interaction.

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion's impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.

Hierarchical self-recognition and response in CSC and non-CSC micro-niches for cancer therapy.

Cancer stem cells (CSCs) characterized by self-renewal, invasiveness, tumorigenicity and resistance to treatment are regarded as the thorniest issues in refractory tumors. We develop a targeted and hierarchical controlled release nano-therapeutic platform (SEED-NPs) that self-identifies and responds to CSC and non-CSC micro-niches of tumors. In non-CSC micro-niche, reactive oxygen species (ROS) trigger the burst release of the chemotherapeutic drug and photosensitizer to kill tumor cells and reduce tumor volume by combining chemotherapy and photodynamic therapy (PDT). In CSC micro-niche, the preferentially released differentiation drug induces CSC differentiation and transforms CSCs into chemotherapy-sensitive cells. SEED-NPs exhibit an extraordinary capacity for downregulating the stemness of CD44+/CD24- SP (side population) cell population both in vitro and in vivo, and reveal a 4-fold increase of tumor-targeted accumulation. Also, PDT-generated ROS promote the formation of tunneling nanotubes and facilitate the divergent network transport of drugs in deep tumors. Moreover, ROS in turn promotes CSC differentiation and drug release. This positive-feedback-loop strategy enhances the elimination of refractory CSCs. As a result, SEED-NPs achieve excellent therapeutic effects in both 4T1 SP tumor-bearing mice and regular 4T1 tumor-bearing mice without obvious toxicities and eradicate half of mice tumors. SEED-NPs integrate differentiation, chemotherapy and PDT, which proved feasible and valuable, indicating that active targeting and hierarchical release are necessary to enhance antitumor efficacy. These findings provide promising prospects for overcoming barriers in the treatment of CSCs.

Reinforced Immunogenic Endoplasmic Reticulum Stress and Oxidative Stress via an Orchestrated Nanophotoinducer to Boost Cancer Photoimmunotherapy.

Cancer progression and treatment-associated cellular stress impairs therapeutic outcome by inducing resistance. Endoplasmic reticulum (ER) stress is responsible for core events. Aberrant activation of stress sensors and their downstream components to disrupt homeostasis have emerged as vital regulators of tumor progression as well as response to cancer therapy. Here, an orchestrated nanophotoinducer (ERsNP) results in specific tumor ER-homing, induces hyperthermia and mounting oxidative stress associated reactive oxygen species (ROS), and provokes intense and lethal ER stress upon near-infrared laser irradiation. The strengthened "dying" of ER stress and ROS subsequently induce apoptosis for both primary and abscopal B16F10 and GL261 tumors, and promote damage-associated molecular patterns to evoke stress-dependent immunogenic cell death effects and release "self-antigens". Thus, there is a cascade to activate maturation of dendritic cells, reprogram myeloid-derived suppressor cells to manipulate immunosuppression, and recruit cytotoxic T lymphocytes and effective antitumor response. The long-term protection against tumor recurrence is realized through cascaded combinatorial preoperative and postoperative photoimmunotherapy including the chemokine (C-C motif) receptor 2 antagonist, ERsNP upon laser irradiation, and an immune checkpoint inhibitor. The results highlight great promise of the orchestrated nanophotoinducer to exert potent immunogenic cell stress and death by reinforcing ER stress and oxidative stress to boost cancer photoimmunotherapy.

A 5 × 200 Gbps microring modulator silicon chip empowered by two-segment Z-shape junctions.

Optical interconnects have been recognized as the most promising solution to accelerate data transmission in the artificial intelligence era. Benefiting from their cost-effectiveness, compact dimensions, and wavelength multiplexing capability, silicon microring resonator modulators emerge as a compelling and scalable means for optical modulation. However, the inherent trade-off between bandwidth and modulation efficiency hinders the device performance. Here we demonstrate a dense wavelength division multiplexing microring modulator array on a silicon chip with a full data rate of 1 Tb/s. By harnessing the two individual p-n junctions with an optimized Z-shape doping profile, the inherent trade-off of silicon depletion-mode modulators is greatly mitigated, allowing for higher-speed modulation with energy consumption of sub-ten fJ/bit. This state-of-the-art demonstration shows that all-silicon modulators can practically enable future 200 Gb/s/lane optical interconnects.

All-silicon microring avalanche photodiodes with a >65 A/W response.

We report an all-Si microring (MRR) avalanche photodiode (APD) with an ultrahigh responsivity (R) of 65 A/W, dark current of 6.5 µA, and record gain-bandwidth product (GBP) of 798 GHz at -7.36 V. The mechanisms for the high responsivity have been modelled and investigated. Furthermore, open eye diagrams up to 20 Gb/s are supported at 1310 nm at -7.36 V. The device is the first, to the best of our knowledge, low cost all-Si APD that has potential to compete with current commercial Ge- and III-V-based photodetectors (PDs). This shows the potential to make the all-Si APD a standard "black-box" component in Si photonics CMOS foundry platform component libraries.

Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies.

Despite the promising potential of cancer vaccine, their efficacy has been limited in clinical trials and improved methods are urgently needed. Here we designed a nanovaccine platform that contains dendritic cell derived exosomes carriers and patient-specific neoantigens for individualized immunotherapies. The nanovaccine exhibited convenient cargo loading and prolonged cargo transportation to the lymph nodes, followed by eliciting potent antigen specific broad-spectrum T-cell and B-cell-mediated immune responses with great biosafety and biocompatibility. Strikingly, delivery of neoantigen-exosome nanovaccine significantly prohibited tumor growth, prolonged survival, delayed tumor occurrences with long-term memory, eliminated the lung metastasis in the therapeutic, prophylactic and metastatic B16F10 melanoma as well as therapeutic MC-38 models, respectively. Additionally, exosome-based nanovaccine demonstrated synergistic antitumor response superior to liposomal formulation due to presence of exosomal proteins. Collectively, our research indicated improved strategies for cell free vaccines and suggested exosome-based nanoplatform for cancer immunotherapy and personalized nanotechnology. These findings represent a powerful pathway to generate individualized nanovaccine rapidly for clinical application.

Radiative anti-parity-time plasmonics.

Space and guided electromagnetic waves, as widely known, are two crucial cornerstones in extensive wireless and integrated applications respectively. To harness the two cornerstones, radiative and integrated devices are usually developed in parallel based on the same physical principles. An emerging mechanism, i.e., anti-parity-time (APT) symmetry originated from non-Hermitian quantum mechanics, has led to fruitful phenomena in harnessing guided waves. However, it is still absent in harnessing space waves. Here, we propose a radiative plasmonic APT design to harness space waves, and experimentally demonstrate it with subwavelength designer-plasmonic structures. We observe two exotic phenomena unrealized previously. Rotating polarizations of incident space waves, we realize polarization-controlled APT phase transition. Tuning incidence angles, we observe multi-stage APT phase transition in higher-order APT systems, constructed by using the scalability of leaky-wave couplings. Our scheme shows promise in demonstrating novel APT physics, and constructing APT-symmetry-empowered radiative devices.

NMR-based metabonomics reveals the dynamic effect of electro-acupuncture on central nervous system in gastric mucosal lesions (GML) rats.

BACKGROUND: Gastric mucosal lesions (GML) are common in gastric diseases and seriously affect the quality of life. There are inevitable side effects in drug therapy. Acupuncture is an important part of traditional Chinese medicine. Electro-acupuncture (EA) has unique curative effect in treatment of GML. However, there are still few reports on the central mechanism of electro-acupuncture in treatment of GML. In this study, NMR metabonomics was used to explore the central metabolic change mechanism of electro-acupuncture in treatment of GML. METHODS: SD rats were randomly divided into Control, GML and EA groups. According to different intervention time, each group was further divided into 3 subgroups. This study mainly established GML model rats by 75% ethanol. Dynamic expressions of metabolites in cerebral cortex and medulla were observed by 1D 1H Nuclear Magnetic Resonance (NMR) metabolomics, combined with gastric mucosal histopathological examination to evaluate the time-effect relationship of electro-acupuncture at Zusanli (ST36) and Liangmen (ST21) points for 1 day, 4 days and 7 days treatment of GML. RESULTS: The results showed that the repair effect of electro-acupuncture on gastric mucosal injury was the most obvious in 4 days and stable in 7 days, and 4 days electro-acupuncture can effectively inhibit GML gastric mucosal inflammation and the expression of inflammatory cells. Meanwhile, the NMR spectrum results of medulla and cerebral cortex showed that, 21 potential metabolites were identified to participate in the mechanism of pathogenesis of GML and the regulation of electro-acupuncture, including 15 in medulla and 10 in cerebral cortex. Metabolic pathway analysis showed that the differential metabolites involved 19 metabolic pathways, which could be divided into energy, neurotransmitters, cells and cell membrane and antioxidation according to their functions. The correlation analysis of stomach, medulla and cerebral cortex shows that the stimulation signal of GML may reach the cerebral cortex from the stomach through medulla, and electro-acupuncture can treat GML by regulating the central nervous system (CNS). CONCLUSIONS: 4 days electro-acupuncture treatment can significantly improve gastric mucosal injury, and the curative effect tends to be stable in 7 days treatment. Meanwhile, the pathogenesis of GML and the efficacy of electro-acupuncture involve metabolic pathways such as energy, neurotransmitters, cells and antioxidation, and electro-acupuncture can treat GML by regulating CNS.

Near 100% external quantum efficiency 1550-nm broad spectrum photodetector.

We report InGaAs/InP based p-i-n photodiodes with an external quantum efficiency (EQE) above 98% from 1510 nm to 1575 nm. For surface normal photodiodes with a diameter of 80 µm, the measured 3-dB bandwidth is 3 GHz. The saturation current is 30.5 mA, with an RF output power of 9.3 dBm at a bias of -17 V at 3 GHz.

Engineered Microglia Potentiate the Action of Drugs against Glioma Through Extracellular Vesicles and Tunneling Nanotubes.

Gliomas remain difficult to treat because of their metastatic and recurrent nature and the existence of the blood-brain barrier (BBB), which impedes drug delivery. Microglia, the resident macrophages in the CNS, can be recruited by gliomas and can penetrate the tumor. In this study, microglia (BV2 cells) are used as transport vectors to deliver paclitaxel for the treatment of glioma. To avoid paclitaxel toxicity in microglia, liposomes are first employed to isolate the drug from BV2 cells. Dipalmitoyl phosphatidylserine (DPPS), as an "eat me" signal, is doped into liposomes to amplify their phagocytosis by microglia. This study demonstrates that engineered microglia can cross the BBB, independently migrate toward gliomas, and transfer cargo to glioma cells. Of note, extracellular vesicles and tunneling nanotubes are found to offer unique modes of cargo transportation between microglia and glioma cells. In vivo, the engineered drug-loaded microglia has a high ability to target the brain, penetrate glioma, and suppress tumor progression, supporting the notion that the use of engineered microglia is a potential strategy for the treatment of glioma. These findings present new opportunities for exploration into the use of microglia as transport vectors to deliver therapeutic agents through specific membrane nanotubes and vesicles.

Phototherapy and anti-GITR antibody-based therapy synergistically reinvigorate immunogenic cell death and reject established cancers.

Phototherapy and immunogenic cell death (ICD) are powerful strategies to fight cancer. However, their therapeutic outcomes are diminished by immunosuppressive and hypoxia microenvironment. Herein, a photo-based, immunomodulating and hypoxia-alleviated nanosystem, PDA-ICG@CAT-DTA-1, is proposed to achieve the synergism between phototherapy and immunotherapy. Catalase (CAT) and anti-GITR antibody (DTA-1) are loaded to photothermal agent and photosensitizer composed PDA-ICG nanoparticles. The PDA-ICG@CAT-DTA-1 exhibits intrinsic local hyperthermia and enhanced ROS generation in tumor, and abrogates tumor immune suppression. It results in reduction of intratumoral FOXP3+ regulatory T cells (4.3-fold) and increase of CD4+ effector T cells (1.5-fold) compare with the control, and promotes damage associated molecular patterns generation to reinvigorate ICD effect. The potent antitumor of PDA-ICG@CAT-DTA-1 is proved in 4T1 bilateral tumor-bearing mice, with inhibition ratio of 95.1% for primary cancers and 68.7% for abscopal cancers. Our findings highlight great promise of the constructed versatility nanosystem to fix bottlenecks for cancer therapy.

Photonic generation of pulsed microwave signals in the X-, Ku- and K-band.

Photonic microwave generation of high-power pulsed signals in the X-, Ku- and K-band using charge-compensated MUTC photodiodes is demonstrated. The impulse photoresponse without modulation showed a maximum peak voltage of 38.3 V and full-width at half-maximum of 30 ps. High power pulsed microwave signals at 10, 17 and 22 GHz with peak power up to 44.2 dBm (26.3 W), 41.6 dBm (14.5 W) and 40.6 dBm (11.5 W) were achieved, respectively.

Albumin-Based Nanotheranostic Probe with Hypoxia Alleviating Potentiates Synchronous Multimodal Imaging and Phototherapy for Glioma.

Highly infiltrative and invasive glioma cells obscure the boundary between tumor and normal brain tissue, making it extremely difficult to precisely diagnose and completely remove. The combination of multimodal imaging with effective treatments to diagnose precisely and guide surgery and therapy accurately is desperately needed for glioma in the brain. Here, we report a biomimetic catalase-integrated-albumin phototheranostic nanoprobe (ICG/AuNR@BCNP) to realize multimodal imaging, amplify phototherapy, and guide surgery for glioma after penetrating the blood-brain barrier, accumulating into deep-seated glioma via albumin-binding protein mediated transportation. The phototheranostic nanoprobe enabled fluorescence, photoacoustic, and infrared thermal imaging with desirable detecting depth and high signal-to-background ratio for clearly differentiating brain tumors from surrounding tissues. Meanwhile, the nanoprobe could effectively induce local hyperthermia and promote the level of singlet oxygen based on alleviated hypoxic glioma microenvironment by decomposing endogenous hydrogen peroxide to oxygen to amplify phototherapy. Thus, significant inhibition of glioma growth, extended survival time, alleviated tumor hypoxia, improved apoptosis, and antiangiogenesis effects were exhibited in several animal models including the periphery and the brain through intravenous or intratumoral injection, meanwhile with low toxicity to normal tissue. The phototherapy was also guided by the assistance of external bioluminescence, magnetic resonance, and positron emission tomography imaging. Moreover, the nanoprobe could accurately guide the glioma resection. These results suggest that the phototheranostic nanoprobe is a promising nanoplatform specifically for glioma to achieve multimodal diagnosis, effective phototherapy, and accurate imaging-guided surgery.

Low-photon-number optical switch and AND/OR logic gates based on quantum dot-bimodal cavity coupling system.

We propose a new scheme based on quantum dot-bimodal cavity coupling system to realize all-optical switch and logic gates in low-photon-number regime. Suppression of mode transmission due to the destructive interference effect is theoretically demonstrated by driving the cavity with two orthogonally polarized pulsed lasers at certain pulse delay. The transmitted mode can be selected by designing laser pulse sequence. The optical switch with high on-off ratio emerges when considering one driving laser as the control. Moreover, the AND/OR logic gates based on photon polarization are achieved by cascading the coupling system. Both proposed optical switch and logic gates work well in ultra-low energy magnitude. Our work may enable various applications of all-optical computing and quantum information processing.

The sensing characteristics of plasmonic waveguide with a ring resonator.

A surface plasmon polaritons (SPPs) refractive index sensor which consists of two metal-insulator-metal (MIM) waveguides coupled to each other by a ring resonator is proposed. The transmission properties are numerically simulated by finite element method. The sensing characteristics of such structure are systematically analyzed by investigating the transmission spectrum. The results indicate that there exist three resonance peaks in the transmission spectrum, and all of which have a linear relationship with the refractive index of the material under sensing. Through the optimization of structural parameters, we achieve a theoretical value of the refractive index sensitivity as high as 3460nmRIU(-1). Furthermore, this structure can also be used as a temperature sensor with temperature sensitivity of 1.36nm/°C. This work paves the way toward sensitive nanometer scale refractive index sensor and temperature sensor for design and application.