Search for light dark matter from atmosphere in PandaX-4T

We report a search for light dark matter produced through the cascading decay of $\eta$ mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne$\cdot$year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at $5.9 \times 10^{-37}{\rm cm^2}$ for dark matter mass of $0.1$ MeV$/c^2$ and mediator mass of 300 MeV$/c^2$. The lowest upper limit of $\eta$ to dark matter decay branching ratio is $1.6 \times 10^{-7}$

Tumor-targeted upconverting nanoplatform constructed by host-guest interaction for near-infrared-light-actuated synergistic photodynamic-/chemotherapy

The strategic combination of photodynamic therapy and chemotherapy has emerged as a promising treatment option for various tumor indications, which not only expands our understanding of each individual modality but also reveals new opportunities to achieve superadditive benefit via exploring their internal synergy rather than simple mixing. In this study, dual-emissive upconverting nanoparticle (UCNP) was employed to bridge the two treatment regimens to synergistically reinforce the therapeutic efficacy. The UCNP-based drug delivery nanoplatform was first co-loaded with 1,8-dihydroxy-3-methylanthraquinone (DHMA) photosensitizers and UV-activatable camptothecin prodrug (NBCCPT) and then complexed with biofunctional β-cyclodextrin species (β-CD-PEG-LA) via highly specific host-guest interactions to cap the camptothecin prodrug conjugated on the nanoparticle surface. The supramolecularly attached β-CD-PEG-LA could not only enhance the aqueous dispersity of the nanocarriers and prevent DHMA leakage, but also imbues targeting effect against asialoglycoprotein receptor-overexpressing tumor cells. The UCNP core would convert the NIR excitation (980 nm) into localized UV (360 nm) and visible (480 nm) emissions, of which the former would cleave the nitrobenzene linker to restore the cytotoxicity of CPT while the latter could excite the photosensitizer to generate reactive oxygen species (ROS). In addition to the photodynamic damage, the light-generated ROS could also facilitate the endo/lysosomal escape of the endocytosed nanoparticles and improve the overall antitumor potency in a synergistic manner.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)This research is supported by the National Natural Science Foundation of China (11832008, 51773023, 51602034, 51603024, 51825302, 21734002), National Key R&D Program of China (2016YFC1100300, 2017YFB0702603), Innovation Project on Industrial Generic Key Technologies of Chongqing (cstc2015zdcy-ztzx120003), Natural Science Foundation of Chongqing Municipal Government (cstc2018jcyjAX0368), People's Livelihood Special Innovation Projects of Chongqing CSTC (cstc2017shmsA130071), Fundamental Research Funds for the Central Universities (2018CDQYSM0036), Innovation Team in University of Chongqing Municipal Government (CXTDX201601002), Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A1883c0005) and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03)

Construction and Synthesis of MoS₂/Biocarbon Composites for Efficient Visible Light-Driven Catalytic Degradation of Humic Acid

MoS2/bio-template carbon composite materials with outstanding photocatalytic degradation performance were constructed and synthesized by an impregnation–hydrothermal–calcination (IHC) method. Composites of the same type were synthesized by a direct-impregnation–calcination (DIC) method for comparison. The results showed that calcination process was obtained from biotemplate carbon with preserved structure. IHC method obtained petal-like MoS2, while DIC method obtained needle-like MoS2. The composite material exhibits adsorption–catalytic degradation performance. Driven by visible light, the photocatalytic degradation efficiency of the composites synthesized by IHC method for humic acid reached 98.73% after 150 min of illumination

Construction and Synthesis of MoS2/Biocarbon Composites for Efficient Visible Light-Driven Catalytic Degradation of Humic Acid

MoS2/bio-template carbon composite materials with outstanding photocatalytic degradation performance were constructed and synthesized by an impregnation–hydrothermal–calcination (IHC) method. Composites of the same type were synthesized by a direct-impregnation–calcination (DIC) method for comparison. The results showed that calcination process was obtained from biotemplate carbon with preserved structure. IHC method obtained petal-like MoS2, while DIC method obtained needle-like MoS2. The composite material exhibits adsorption–catalytic degradation performance. Driven by visible light, the photocatalytic degradation efficiency of the composites synthesized by IHC method for humic acid reached 98.73% after 150 min of illumination

Stepwise mini-incision microdissection testicular sperm extraction in NOA patients with a history of cryptorchidism: a case–control study

Abstract Background Although the orchiopexy is recommended for cryptorchidism to preserve male fertility, non-obstructive azoospermia (NOA) may occur in adulthood. Fortunately, a great many of azoospermic men may obtain sperm by microdissection testicular sperm extraction (mTESE). Due to the potential injuries caused by testicular diagnostic biopsy and vascular damage at the time of orchidopexy, minimal invasiveness is particularly important during mTESE, aims to reduce the surgical damage and avoids secondary testicular failure. This comparative study aims to investigate the efficacy of stepwise mini-incision mTESE technique by comparison with standard mTESE in the treatment of NOA patients with a history of cryptorchidism. Results A total of 73 mTESE procedures were divided into two groups: Group 1 included 37 cases performed by stepwise mini-incision mTESE, while Group 2 included 36 cases with standard mTESE. The overall sperm retrieval rate (SRR) in the two groups was 68.5% (50/73), with no significant difference in SRR between Group 1 (78.4%, 29/37) and Group 2 (58.3%, 21/36) (P = 0.1). In addition, 46.0% of the patients (17/37) obtained sperm in the first mini-incision step in Group 1, which was also equal to an overall SRR in Group 2 (58.3%, 21/36) (P = 0.3). The operation time in Group 1 (72.6 ± 33.9 min) was significantly shorter than that in Group 2 (90.4 ± 36.4 min) (P = 0.04). Patients with an orchidopexy age no more than 10 years old had a higher SRR (79.5%, 31/39) than others (55.9%, 19/34) (P = 0.03). There were no postoperative complications including wound infection, scrotal hematoma, persistent pain, and testicular atrophy during a follow-up period of at least 6 months. Conclusions In conclusion, our study suggests that the stepwise mini-incision mTESE could be a promising approach for sperm retrieval in NOA men with a history of cryptorchidism. While the technique may potentially reduce operation time and surgical invasiveness, further research is needed to validate these findings on a larger scale. The results also suggest that age at orchidopexy may affect SRR and have important implications for the management of cryptorchidism

Distinct Expression Profiles and Novel Targets of MicroRNAs in Human Spermatogonia, Pachytene Spermatocytes, and Round Spermatids between OA Patients and NOA Patients

Human spermatogenesis includes three main stages, namely, the mitosis of spermatogonia, meiosis of spermatocytes, and spermiogenesis of spermatids, which are precisely regulated by epigenetic and genetic factors. Abnormality of epigenetic and genetic factors can result in aberrant spermatogenesis and eventual male infertility. However, epigenetic regulators in controlling each stage of normal and abnormal human spermatogenesis remain unknown. Here, we have revealed for the first time the distinct microRNA profiles in human spermatogonia, pachytene spermatocytes, and round spermatids between obstructive azoospermia (OA) patients and non-obstructive azoospermia (NOA) patients. Human spermatogonia, pachytene spermatocytes, and round spermatids from OA patients and NOA patients were isolated using STA-PUT velocity sedimentation and identified by numerous hallmarks for these cells. RNA deep sequencing showed that 396 microRNAs were differentially expressed in human spermatogonia between OA patients and NOA patients and 395 differentially expressed microRNAs were found in human pachytene spermatocytes between OA patients and NOA patients. Moreover, 378 microRNAs were differentially expressed in human round spermatids between OA patients and NOA patients. The differential expression of numerous microRNAs identified by RNA deep sequencing was verified by real-time PCR. Moreover, a number of novel targeting genes for microRNAs were predicted using various kinds of software and further verified by real-time PCR. This study thus sheds novel insights into epigenetic regulation of human normal spermatogenesis and the etiology of azoospermia, and it could offer new targets for molecular therapy to treat male infertility

Tumor‐Microenvironment‐Activated In Situ Self‐Assembly of Sequentially Responsive Biopolymer for Targeted Photodynamic Therapy

A sequentially responsive photosensitizer-integrated biopolymer is developed for tumor-specific photodynamic therapy, which is capable of forming long-retained aggregates in situ inside tumor tissues. Specifically, the photosensitizer zinc phthalocyanine (ZnPc) is conjugated with polyethylene glycol (PEG) via pH-labile maleic acid amide linker and then immobilized onto the hyaluronic acid (HA) chain using a redox-cleavable disulfide linker. The PEG segment can enhance blood circulation of the molecular carrier after intravenous administration and be shed after reaching the acidic tumor microenvironment, allowing the remaining fragment to self-assemble into large clusters in situ to avoid backward diffusion and improve tumor retention. This process is driven by hydrophobic interactions and does not require additional external actuation. The aggregates are then internalized by the tumor cells via HA-facilitated endocytosis, and the high glutathione level in tumor cells eventually leads to the intracellular release of ZnPc to facilitate its interaction with the subcellular lipid structures. This tumor-triggered morphology-based delivery platform is constructed with clinically tested components and could potentially be applied to other hydrophobic therapeutics.National Research Foundation (NRF)Accepted versionX. Wang and M.H. Li contributed equally to this work. This work was financially supported by Natural Science Foundation of China (11832008, 51773023 and 21734002), National Key Technology R&D Program of China (2017YFB0702603 and 2016YFC1100300), Fundamental Research Funds for the Central Universities (2019CDQYSW005), Chongqing Outstanding Young Talent Supporting Program (CQYC201905072), Returning Overseas Scholar Innovation Program (CX2018062), Central University's Basic Scientific Research Business Fee Medical Integration Project (2019CDYGYB004). The work was also supported by the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03)

Low-Intensity Pulsed Ultrasound Alleviates Human Testicular Leydig Cell Senescence In Vitro

Aging has a significant negative impact on human testicular function; steroidogenesis is gradually impaired, and testosterone replacement therapy still has many risks. Low-intensity pulsed ultrasound (LIPUS) has been used as a novel non-invasive treatment for male erectile dysfunction and other fields, and has been shown to increase testosterone levels in animal models. Testosterone is synthesized and secreted by Leydig cells (LCs), and the serum testosterone level decreases after aging due to the LCs senescence. However, the effect of LIPUS on human senescent LCs has not been reported. In this study, human senescent LCs were isolated and stimulated with different energy intensities in vitro, and cell morphology, cell apoptosis, cell proliferation, cell senescence levels, lipid droplet number, testosterone and INSL3 secretion levels were tested and analyzed. Quantitative Polymerase Chain Reaction (QPCR) and Western Blot were performed to compare cell senescence characteristics and the expression profile of key pathways of testosterone secretion, and transcriptome analysis was performed to explore the signaling pathways of LCs alteration after LIPUS stimulation. It was safe and effective to stimulate LCs with the 75 mW/cm2 energy of LIPUS in vitro, which not only improved the senescence phenotype, but also effectively enhanced the secretory function of LCs in vitro, and increased the expression of key pathways of the testosterone synthesis pathway. These results suggest that LIPUS could be used as a novel treatment to human senescent LCs with decreased testosterone secretion levels in vitro

Fibroblast growth factor-5 promotes spermatogonial stem cell proliferation via ERK and AKT activation

Abstract Background Sertoli cells are the most important somatic cells contributing to the microenvironment (named niche) for spermatogonial stem cells (SSCs). They produce amounts of crucial growth factors and structure proteins that play essential roles in the complex processes of male SSCs survival, proliferation, and differentiation. It has been suggested that Sertoli cell abnormalities could result in spermatogenesis failure, eventually causing azoospermia in humans. However, to the end, the gene expression characteristics and protein functions of human Sertoli cells remained unknown. In this study, we aimed to evaluate the effect of fibroblast growth factor-5 (FGF5), a novel growth factor downregulated in Sertoli cells from Sertoli cell-only syndrome (SCOS) patients compared to Sertoli cells from obstructive azoospermia (OA) patients, on SSCs. Methods We compared the transcriptome between Sertoli cell from SCOS and OA patients. Then, we evaluated the expression of FGF5, a growth factor which is downregulated in SCOS Sertoli cells, in human primary cultured Sertoli cells and testicular tissue. Also, the proliferation effect of FGF5 in mice SSCs was detected using EDU assay and CCK-8 assay. To investigate the mechanism of FGF5, Phospho Explorer Array was performed. And the results were verified using Western blot assay. Results Using RNA-Seq, we found 308 differentially expressed genes (DEGs) between Sertoli cells from SCOS and OA patients. We noted and verified that the expression of fibroblast growth factor-5 (FGF5) was higher in Sertoli cells of OA patients than that of SCOS patients at both transcriptional and translational levels. Proliferation assays showed that rFGF5 enhanced the proliferation of mouse SSCs line C18-4 in a time- and dose-dependent manner. Moreover, we demonstrated that ERK and AKT were activated and the expression of Cyclin A2 and Cyclin E1 was enhanced by rFGF5. Conclusion The distinct RNA profiles between Sertoli cells from SCOS and OA patients were identified using RNA-Seq. Also, FGF5, a growth factor that downregulated in SCOS Sertoli cells, could promote SSCs proliferation via ERK and AKT activation