Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress.

OBJECTIVE: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. METHODS: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. RESULTS: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. CONCLUSION: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; 22(4): 494-503.

Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.

Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.

Long range 3D imaging through atmospheric obscurants using array-based single-photon LiDAR.

Single-photon light detection and ranging (LiDAR) has emerged as a strong candidate technology for active imaging applications. In particular, the single-photon sensitivity and picosecond timing resolution permits high-precision three-dimensional (3D) imaging capability through atmospheric obscurants including fog, haze and smoke. Here we demonstrate an array-based single-photon LiDAR system, which is capable of performing 3D imaging in atmospheric obscurant over long ranges. By adopting the optical optimization of system and the photon-efficient imaging algorithm, we acquire depth and intensity images through dense fog equivalent to 2.74 attenuation lengths at distances of 13.4 km and 20.0 km. Furthermore, we demonstrate real-time 3D imaging for moving targets at 20 frames per second in mist weather conditions over 10.5 km. The results indicate great potential for practical applications of vehicle navigation and target recognition in challenging weather.

COVID-19 Vaccination Rates of People Who Use Drugs - Chengdu City, Sichuan Province, China, November 2021 - February 2022.

What is already known about this topic?: Few studies have reported that people who use drugs (PWUDs) have much lower coronavirus disease 2019 (COVID-19) vaccination rates than the general population, especially with no relative information reported in China specifically. What is added by this report?: This study seminally uncovers that the vaccination rate among PWUDs was about 79.34% in one district of Chengdu City, Sichuan Province, China. Assuming that unvaccinated PWUDs with disease records were really not eligible for vaccination, the vaccination rate goes up to 87.25% among the studied PWUDs. The study implies that PWUDs were not left behind in the vaccination drive against COVID-19 in China. What are the implications for public health practice?: In pandemics like COVID-19, government leadership and the overall planning and distribution of public health products are critical in achieving national health equity. However, in order to do this as well as avoid discrimination or exclusion among specific portions of the general population, it's necessary to understand the vaccination rates and behaviors of at-risk groups such as PWUD's.

Compact long-range single-photon imager with dynamic imaging capability.

Single-photon light detection and ranging (LiDAR) has emerged as a strong candidate technology for active imaging applications. Benefiting from the single-photon sensitivity in detection, long-range active imaging can be realized with a low-power laser and a small-aperture transceiver. However, existing kilometer-range active imagers are bulky and have a long data acquisition time. Here we present a compact co-axial single-photon LiDAR system for kilometer-range 3D imaging. A fiber-based transceiver with a 2.5 cm effective aperture was employed to realize a robust and compact architecture, while a tailored temporal filtering approach guaranteed the high signal-to-noise level. Moreover, a micro-electro-mechanical system scanning mirror was adopted to achieve fast beam scanning. In experiment, high-resolution 3D images of different targets up to 12.8 km were acquired to demonstrate the long-range imaging capability. Furthermore, it exhibits the ability to achieve dynamic imaging at five frames per second over a distance of ∼1km. The results indicate potential in a variety of applications such as remote sensing and long-range target detection.

Tetramethylpyrazine Protects Blood-Spinal Cord Barrier Integrity by Modulating Microglia Polarization Through Activation of STAT3/SOCS3 and Inhibition of NF-кB Signaling Pathways in Experimental Autoimmune Encephalomyelitis Mice.

We previously reported that tetramethylpyrazine (TMP) alleviates experimental autoimmune encephalomyelitis (EAE) by decreasing glia activation. Activated microglia has been shown to mediate blood-spinal cord barrier (BSCB) disruption, which is a primary and continuous pathological characteristic of multiple sclerosis (MS). Therefore, in this study, we further investigated whether TMP protects the BSCB integrity by inhibition of glia activation to alleviate EAE. Extravasation of evans blue was used to detect the BSCB disruption. Tumor necrosis factor-α (TNF-α)/interlukine-1ß (IL-1ß) and interlukine-4 (IL-4)/interlukine-10 (IL-10) were determined by enzyme-linked immunosorbent assay. BV2 glial cells stimulated by interferon-γ (IFN-γ) were co-cultured with human brain microvascular endothelial cells to investigate the effect of TMP on the BSCB disruption. Flow cytometry was used to analyze the microglia phenotype. Western blot was performed to reveal the signaling pathways involved in the microglia activation. In this study, most importantly, we found that TMP protects the BSCB integrity by modulating microglia polarization from M1 phenotype to M2 phenotype through activation of STAT3/SOCS3 and inhibition of NF-кB signaling pathways. Moreover, TMP significantly preserves the tight junction proteins, reduces the secretion of pro-inflammatory cytokines (TNF-α, IL-1ß) and increases the secretion of anti-inflammatory cytokines (IL-4, IL-10) from IFN-γ-stimulated BV2 microglia cells. Consequently, protection of the BSCB integrity leads to alleviation of clinical symptoms and demyelination in EAE mice. Therefore, TMP might be an effective therapeutic agent for cerebral disorders with BBB or BSCB disruption, such as ischemic stroke, MS, and traumatic brain injury.

Super-resolution single-photon imaging at 8.2 kilometers.

Single-photon light detection and ranging (LiDAR), offering single-photon sensitivity and picosecond time resolution, has been widely adopted for active imaging applications. Long-range active imaging is a great challenge, because the spatial resolution degrades significantly with the imaging range due to the diffraction limit of the optics, and only weak echo signal photons can return but mixed with a strong background noise. Here we propose and demonstrate a photon-efficient LiDAR approach that can achieve sub-Rayleigh resolution imaging over long ranges. This approach exploits fine sub-pixel scanning and a deconvolution algorithm tailored to this long-range application. Using this approach, we experimentally demonstrated active three-dimensional (3D) single-photon imaging by recognizing different postures of a mannequin model at a stand-off distance of 8.2 km in both daylight and night. The observed spatial (transversal) resolution is ∼5.5 cm at 8.2 km, which is about twice of the system's resolution. This also beats the optical system's Rayleigh criterion. The results are valuable for geosciences and target recognition over long ranges.

[Gene Polymorphism 24 Rare Blood Group Antigens of 11 RBC Blood Group Systems in Manchu Population of Harbin Area in China].

OBJECTIVE: The purpose of this study was to investigate the 24 kinds of antigen gene polymorphism chara-cteristics in 11 RBC blood group systems of Manchu population blood donor in Harbin Area of China, so as to better perform the clinical blood transfusion and to avoid adverse transfusion reactions. METHODS: Twenty-four antigen genes (GYPB (S/S), Duffy, Kell, Dombrock, Diego, Kidd, Scianna, Colton, Lutheran, Yt, Mur) were assessed by the polymerase chain reaction sequence specific primers (PCR-SSP) in 11 blood type systems, including Fya, Fyb; K, K; Doa, Dob; Dia, Dib; JKa, JKb; Sc1,Sc2; Coa, Cob; Lua, Lub; Yta, Ytb; Kpa, Kpb; Mur, Mur2 among 200 Manchus in Harbin. RESULTS: The gene frequency of blood type system in Harbin Manchu GYPB (S/S) was as follows: S=0.0625, s=0.9325; the gene frequency of duffy blood type system: Fya=0.0525, Fyb=0.9475; Gene frequency of Dombrock type system was as follows: Doa=0.1250, Dob=0.8750; Gene frequency of Diego type system: Dia=0.0275, Dib=0.9725; the gene frequency of Kidd blood type system: JKa=0.5650, JKb=0.4350; the gene frequency of Mur blood type system: Mur1 = 0.0050, Mur2 = 0.9950; the Kell, Scianna, Colton, Lutheran and Yt type blood type system displayed a monomorph distribution and the genotype was kkKpbKpb,Sc1Sc1,CoaCoa, LubLub, YtaYta, respectively. CONCLUSION: The distribution of GYPB(S/s),Duffy,Dombrock, Diego, Kidd and Mur blood type system in Harbin Manchu has been found to be characterized by polymorphism, and the distribution of kell, scianna, colton, lutheran and ye blood type system has been found to be characterized by oligomorphism. The gene destribution of dombrock and Kidd blood group systems is unique in Harbin Manchu.

IRGM1 regulates oxidized LDL uptake by macrophage via actin-dependent receptor internalization during atherosclerosis.

Macrophage derived foam cells are actively involved in the initial phase of atherosclerosis. Uptake of modified lipoprotein such as oxidized LDL (oxLDL) is a critical step for foam cell formation. CD36 is the major receptor mediating oxLDL uptake by macrophage. However, the molecular mechanism underlying CD36 mediated oxLDL uptake remains unclear. Here we reported that IRGM1 (IRGM in human), a member of immunity-related small GTPase family, is essential for the actin-dependent CD36 mediated oxLDL uptake by macrophage. IRGM/IRGM1 was highly expressed by macrophage around the atherosclerotic plaque and was up-regulated by oxLDL both in vitro and in vivo. Moreover loss of IRGM/IRMG1 significantly decreased oxLDL uptake in both mouse and human. Furthermore, the IRGM1 knock-out mice displayed impaired CD36 internalization in macrophage, which was associated with the deficiency of F-actin polymerization. These results revealed a novel function of IRGM1 in regulating oxLDL uptake by macrophage during atherosclerosis.