Intercellular Mitochondrial Transfer: The Novel Therapeutic Mechanism for Diseases.

Mitochondria, the dynamic organelles responsible for energy production and cellular metabolism, have the metabolic function of extracting energy from nutrients and synthesizing crucial metabolites. Nevertheless, recent research unveils that intercellular mitochondrial transfer by tunneling nanotubes, tumor microtubes, gap junction intercellular communication, extracellular vesicles, endocytosis and cell fusion may regulate mitochondrial function within recipient cells, potentially contributing to disease treatment, such as nonalcoholic steatohepatitis, glioblastoma, ischemic stroke, bladder cancer and neurodegenerative diseases. This review introduces the principal approaches to intercellular mitochondrial transfer and examines its role in various diseases. Furthermore, we provide a comprehensive overview of the inhibitors and activators of intercellular mitochondrial transfer, offering a unique perspective to illustrate the relationship between intercellular mitochondrial transfer and diseases.

ZIP transporters-regulated Zn2+ homeostasis: A novel determinant of human diseases.

As an essential trace element for organisms, zinc participates in various physiological processes, such as RNA transcription, DNA replication, cell proliferation, and cell differentiation. The destruction of zinc homeostasis is associated with various diseases. Zinc homeostasis is controlled by the cooperative action of zinc transporter proteins that are responsible for the influx and efflux of zinc. Zinc transporter proteins are mainly categorized into two families: Zrt/Irt-like protein (SLC39A/ZIP) family and zinc transporter (SLC30A/ZNT) family. ZIP transporters contain 14 members, namely ZIP1-14, which can be further divided into four subfamilies. Currently, ZIP transporters-regulated zinc homeostasis is one of the research hotspots. Cumulative evidence suggests that ZIP transporters-regulated zinc homeostasis may cause physiological dysfunction and contribute to the onset and progression of diverse diseases, such as cancers, neurological diseases, and cardiovascular diseases. In this review, we initially discuss the structure and distribution of ZIP transporters. Furthermore, we comprehensively review the latest research progress of ZIP transporters-regulated zinc homeostasis in diseases, providing a new perspective into new therapeutic targets for treating related diseases.

Spin-Orbit Excitons in a Correlated Metal: Raman Scattering Study of Sr_{2}RhO_{4}.

Using Raman spectroscopy to study the correlated 4d-electron metal Sr_{2}RhO_{4}, we observe pronounced excitations at 220 meV and 240 meV with A_{1g} and B_{1g} symmetries, respectively. We identify them as transitions between the spin-orbit multiplets of the Rh ions, in close analogy to the spin-orbit excitons in the Mott insulators Sr_{2}IrO_{4} and α-RuCl_{3}. This observation provides direct evidence for the unquenched spin-orbit coupling in Sr_{2}RhO_{4}. A quantitative analysis of the data reveals that the tetragonal crystal field Δ in Sr_{2}RhO_{4} has a sign opposite to that in insulating Sr_{2}IrO_{4}, which enhances the planar xy orbital character of the effective J=1/2 wave function. This supports a metallic ground state, and suggests that c-axis compression of Sr_{2}RhO_{4} may transform it into a quasi-two-dimensional antiferromagnetic insulator.

[Two new sesquiterpenes in Qi-nan Aquilariae Lignum Resinatum].

This study aimed to investigate the chemical constituents of supercritical extract from Qi-nan Aquilariae Lignum Resinatum by silica gel column chromatography, thin-layer chromatography, and semi-preparative high-performance liquid chromatography. One new elemane-type and one new eudesmane-type sesquiterpene compounds were isolated from the extract, and their structures were identified by MS, UV, IR, NMR, and ECD spectroscopic techniques, and named aquqinanol C(1) and aquqinanol D(2). Both compounds are novel compounds. The neuroprotective effect of the compounds on CORT-induced PC12 cell damage was determined in vitro. The results showed that compounds 1 and 2 exhibited a certain protective effect against CORT-induced damage in PC12 cells.

The REEP family of proteins: Molecular targets and role in pathophysiology.

Receptor expression-enhancing proteins (REEPs) are an evolutionarily conserved protein family that is pivotal to the structure and function of the endoplasmic reticulum (ER). The REEP family can be classified into two major subfamilies in higher species, the REEP1-4 and REEP5-6 subfamilies. Within the REEP1-4 subfamily, REEP1 and REEP2 are closely related, and REEP3 and REEP4 are similarly related. The REEP family is widely distributed in various tissues. Recent studies indicate that the REEP family is involved in many pathological and physiological processes, such as ER morphogenesis and remodeling, microtubule cytoskeleton regulation, and the trafficking and expression of G protein-coupled receptors (GPCRs). Moreover, the REEP family plays crucial roles in the occurrence and development of many diseases, including neurological diseases, diabetes, retinal diseases, cardiac diseases, infertility, obesity, oligoarticular juvenile idiopathic arthritis (OJIA), COVID-19, and cancer. In the present review, we describe the distribution and structure of the REEP family. Furthermore, we summarize the functions and the associated diseases of this family. Based on the pleiotropic actions of the REEP family, the study of its family members is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.

Therapeutic potential of traditional Chinese medicine in atherosclerosis: A review.

Atherosclerosis is the onset of endothelial cell damage and is characterized by abnormal accumulation of fibrinogen and lipid in large and middle arteries. Recent researches indicate that traditional Chinese medicine including Notoginseng Radix et Rhizoma, Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Fructus Crataegi, Glycyrrhizae Radix et Rhizoma, Polygoni Multiflori Radix, Fructus Lycii, and Coptidis Rhizoma have therapeutic effects on atherosclerosis. Furthermore, the pharmacological roles of these kinds of traditional Chinese medicine in atherosclerosis refer to endothelial function influences, cell proliferation and migration, platelet aggregation, thrombus formation, oxidative stress, inflammation, angiogenesis, apoptosis, autophagy, lipid metabolism, and the gut microbiome. Traditional Chinese medicine may serve as potential and effective anti-atherosclerosis drugs. However, a critical study has shown that Notoginseng Radix et Rhizoma may also have toxic effects including pustules, fever, and elevate circulating neutrophil count. Further high-quality studies are still required to determine the clinical safety and efficacy of traditional Chinese medicine and its active ingredients.

NCOA2 promotes lytic reactivation of Kaposi's sarcoma-associated herpesvirus by enhancing the expression of the master switch protein RTA.

Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) is important for persistent infection in the host as well as viral oncogenesis. The replication and transcription activator (RTA) encoded by KSHV ORF50 plays a central role in the switch from viral latency to lytic replication. Given that RTA is a transcriptional activator and RTA expression is sufficient to activate complete lytic replication, RTA must possess an elaborate mechanism for regulating its protein abundance. Previous studies have demonstrated that RTA could be degraded through the ubiquitin-proteasome pathway. A protein abundance regulatory signal (PARS), which consists of PARS I and PARS II, at the C-terminal region of RTA modulates its protein abundance. In the present study, we identified a host protein named Nuclear receptor coactivator 2 (NCOA2), which can interact with RTA in vitro and in vivo. We further showed that NCOA2 binds to the PARS II domain of RTA. We demonstrated that NCOA2 enhances RTA stability and prevents the proteasome-mediated degradation of RTA by competing with MDM2, an E3 ubiquitin ligase of RTA that interacts with the PARS II domain. Moreover, overexpression of NCOA2 in KSHV-infected cells significantly enhanced the expression level of RTA, which promotes the expression of RTA downstream viral lytic genes and lytic replication. In contrast, silencing of endogenous NCOA2 downregulated the expression of viral lytic genes and impaired viral lytic replication. Interestingly, we also found that RTA upregulates the expression of NCOA2 during lytic reactivation. Taken together, our data support the conclusion that NCOA2 is a novel RTA-binding protein that promotes RTA-driven lytic reactivation by increasing the stability of RTA, and the RTA-NCOA2 positive feedback regulatory loop plays an important role in KSHV reactivation.

Regulated aberrant amygdala functional connectivity in premenstrual syndrome via electro-acupuncture stimulation at sanyinjiao acupoint（SP6）.

Background: Acupuncture is an effective therapy for premenstrual syndrome (PMS). However, the mechanisms behind this method are still unclear. Our previous study found that aberrant amygdala resting-state functional networks were involved in PMS. Thereby, a deep investigation on the alterations of amygdala resting-state functional networks induced by acupuncture stimulation might contribute to a better understanding of the intricate mechanisms of acupuncture treatment on PMS. Methods: Twenty three PMS patients were recruited in this study. All patients received a 6-minute electro-acupuncture stimulation (EAS) at Sanyinjiao acupoint (SP6) and underwent two 6-minute resting-state fMRI scannings before and after EAS. With amygdala as the seed region, functional connectivity (FC) method was adopted to examine EAS-related modulation of intrinsic connectivity in PMS patients by comparing pre-EAS. Results: The results showed that EAS at SP6 induced increased FC between the left amygdala and brainstem, right hippocampus, and decreased FC between the left amygdala and left thalamus, bilateral supplementary motor area (SMA). Moreover, the results also showed that EAS at SP6 induced increased FC between the right amygdala and brainstem, right hippocampus, right orbitofrontal cortex, bilateral anterior cingulate cortex (ACC), and decreased FC between the right amygdala and right SMA. Conclusions: Based on the results of our previous study, our findings might improve our understanding of neural mechanisms behind acupuncture effects on PMS.

Altered fractional amplitude of low-frequency fluctuation in women with premenstrual syndrome via acupuncture at Sanyinjiao (SP6).

BACKGROUND: Premenstrual syndrome (PMS) is a prevalent gynecological disease and is significantly associated with abnormal neural activity. Acupuncture is an effective treatment on PMS in clinical practice. However, few studies have been performed to investigate whether acupuncture might modulate the abnormal neural activity in patients with PMS. Thereby, the aim of the study was to assess alterations of the brain activity induced by acupuncture stimulation in PMS patients. METHODS: Twenty PMS patients were enrolled in this study. All patients received a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) scan before and after electro-acupuncturing stimulation (EAS) at Sanyinjiao (SP6) acupoint in the late luteal phase of menstrual. Fractional amplitude of low-frequency fluctuation (fALFF) method was applied to examine the EAS-related brain changes in PMS patients. RESULTS: Compared with pre-EAS at SP6, increased fALFF value in several brain regions induced by SP6, including brainstem, right thalamus, bilateral insula, right paracentral lobule, bilateral cerebellum, meanwhile, decreased fALFF in the left cuneus, right precuneus, left inferior temporal cortex. CONCLUSIONS: Our findings provide imaging evidence to support that SP6-related acupuncture stimulation may modulate the neural activity in patients with PMS. This study may partly interpret the neural mechanisms of acupuncture at SP6 which is used to treat PMS patients in clinical. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn . The Clinical Trial Registration Number is ChiCTR-OPC-15005918, registry in 29/01/2015.

Kitaev Spin Liquid in 3d Transition Metal Compounds.

We study the exchange interactions and resulting magnetic phases in the honeycomb cobaltates. For a broad range of trigonal crystal fields acting on Co^{2+} ions, the low-energy pseudospin-1/2 Hamiltonian is dominated by bond-dependent Ising couplings that constitute the Kitaev model. The non-Kitaev terms nearly vanish at small values of trigonal field Δ, resulting in spin liquid ground state. Considering Na_{3}Co_{2}SbO_{6} as an example, we find that this compound is proximate to a Kitaev spin liquid phase, and can be driven into it by slightly reducing Δ by ∼20 meV, e.g., via strain or pressure control. We argue that, due to the more localized nature of the magnetic electrons in 3d compounds, cobaltates offer the most promising search area for Kitaev model physics.

Pseudo-Jahn-Teller Effect and Magnetoelastic Coupling in Spin-Orbit Mott Insulators.

The consequences of the Jahn-Teller (JT) orbital-lattice coupling for magnetism of pseudospin J_{eff}=1/2 and J_{eff}=0 compounds are addressed. In the former case, represented by Sr_{2}IrO_{4}, this coupling generates, through the so-called pseudo-JT effect, orthorhombic deformations of a crystal concomitant with magnetic ordering. The orthorhombicity axis is tied to the magnetization and rotates with it under magnetic field. The theory resolves a number of puzzles in Sr_{2}IrO_{4} such as the origin of in-plane magnetic anisotropy and magnon gaps, metamagnetic transition, etc. In J_{eff}=0 systems, the pseudo-JT effect leads to spin-nematic transition well above magnetic ordering, which may explain the origin of "orbital order" in Ca_{2}RuO_{4}.

A nanohybrid composed of MoS2 quantum dots and MnO2 nanosheets with dual-emission and peroxidase mimicking properties for use in ratiometric fluorometric detection and cellular imaging of glutathione.

A nanohybrid probe was fabricated from manganese dioxide nanosheets (MnO2 NSs), molybdenum disulfide quantum dots (MoS2 QDs) and o-phenylenediamine (OPD) for ratiometric detection of glutathione (GSH) in aqueous solutions and living cells. The MoS2 QDs act as the fluorescent "turn off-on" units. The MnO2 NSs have 3 functions, viz. (a) as fluorescence quencher, (b) as fluorescence initiator for oxidized OPD (ox OPD) and (c) as selective recognizer of GSH. The quenched blue fluorescence of the MoS2 QDs can be restored by introducing GSH that reduces the MnO2 NSs. However, the green fluorescence of ox OPD is decreased through the loss of peroxidase activity of MnO2 NSs in the presence of GSH. Therefore, the ratio of the fluorescence intensities at 560 and 400 nm (from ox OPD and MoS2 QDs, respectively) linearly decreases with increasing concentrations of GSH. Under the optimal conditions, the detection limit for GSH is as low as 90 nM. The method was successfully applied to the determination of GSH in human serum samples. This nanohybrid also is shown to be membrane-permeable and to have low cytotoxicity. This paved the way to intracellular sensing of GSH in living normal HFF and cancerous HeLa cells. Additionally, by combining with logic gate, this assay was successfully applied to visually discriminate changes in the intracellular GSH. The combination of ratiometric fluorometry and peroxidase mimicking can provide a wide range of application in bioanalysis and intracellular imaging. Graphical abstract Schematic representation of the ratiometric fluorometric detection and cellular imaging of glutathione using a nanohybrid composed of MoS2 quantum dots and MnO2 nanosheets with dual (blue and green emission and peroxidase mimicking properties.

Hippocampal fractional amplitude of low-frequency fluctuation and functional connectivity changes in premenstrual syndrome.

PURPOSE: To investigate differences in hippocampal activity between premenstrual syndrome (PMS) patients and healthy controls, to elucidate the neural mechanisms of PMS. MATERIALS AND METHODS: Twenty female patients with PMS (PMS group) and 21 healthy controls (HC group) underwent a single-shot gradient-recalled echo planar imaging (EPI) sequence scan during the luteal phase in 3.0 Tesla MRI. Spontaneous neural activity in hippocampus (HIPP) was measured by fractional amplitude of low-frequency fluctuation (fALFF). Functional connectivity (FC) was used to examine the neural networks of PMS patients by selecting the abnormal HIPP as the seed region. All participants completed a daily record of severity of problems (DRSP) questionnaire to measure the severity of clinical symptoms. RESULTS: Results from a two-sample t-test showed increased left HIPP fALFF in the PMS group compared with the HC group (P = 0.042), while there was no between-group difference of fALFF in the right HIPP (P = 0.1011). A secondary analysis using a two-sample t-test with the left HIPP as the seed region, the results revealed that the PMS group exhibited increased FC between the left HIPP and left medial prefrontal cortex (mPFC), left posterior cingulate cortex (PCC), right middle cingulate cortex (MCC), and bilateral precentral cortex (PC), while decreased FC between the left HIPP and right orbitofrontal cortex (OFC). Moreover, the PMS group exhibited higher DRSP scores, which were positively correlated (r = 0.64, P = 0.003) with FC between the left HIPP and mPFC during the luteal phase. CONCLUSION: Altered spontaneous neural activity and connectivity of left HIPP may be involved in PMS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:545-553.

Larger volume and different functional connectivity of the amygdala in women with premenstrual syndrome.

OBJECTIVES: To assess structural and functional changes of the amygdala due to premenstrual syndrome (PMS) using magnetic resonance imaging (MRI). METHODS: Twenty PMS patients and 21 healthy control (HC) subjects underwent a 6-min resting-state fMRI scan during the luteal phase as well as scanning high-resolution T1-weighted images. Subcortical amygdala-related volume and functional connectivity (FC) were estimated between the two groups. Each subject completed a daily record of severity of problems (DRSP) to measure the severity of clinical symptoms. RESULTS: Greater bilateral amygdalae volumes were found in PMS patients compared with HC subjects, and PMS patients had increased FC between the amygdala and certain regions of the frontal cortex (e.g. medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), right precentral gyrus), the right temporal pole and the insula, as well as decreased FC between the bilateral amygdalae and the right orbitofrontal cortex and right hippocampus. The strength of FC between the right amygdala and right precentral gyrus, left ACC and left mPFC were significantly and positively correlated with DRSP scores in PMS patients. CONCLUSIONS: Our findings may improve our understanding of the neural mechanisms involved in PMS. KEY POINTS: • Functional and structural MRI used to explore amygdala in PMS patients. • Aberrant amygdala structural and functional connectivity were found in PMS patients. • Amygdala strength FC was positively correlated with individual clinical symptom scores.

MoS2 nanosheets with peroxidase mimicking activity as viable dual-mode optical probes for determination and imaging of intracellular hydrogen peroxide.

The authors describe a dual-mode (colorimetric-fluorometric) nanoprobe for H2O2 that was fabricated by covering molybdenum disulfide nanosheets (MoS2 NS) with ortho-phenylenediamine (OPD). The probe (OPD-MoS2 NS) was applied to the optical determination of H2O2, to the quantitation of cell numbers, and to the detection of intracellular concentrations of H2O2. Oxidation by H2O2 leads to a colored and fluorescent product (oxidized OPD) with absorption/excitation/fluorescence peaks at 450/450/557 nm. The nanoprobe can detect H2O2 in down to 500 nM concentrations, and HeLa cells at levels of 100 cells mL-1. The detection limit for intracellular H2O2 is in the 5.5 to 12.6 µM concentration range when the method is applied to cells at levels of 102-106 cells mL-1. Due to its good biocompatibility and easy cell uptake, the nanoprobe also permits sensitive fluorometric imaging of intracellular H2O2. It can also comparatively discriminate the change of intracellular oxidation state in living cancerous and normal cells. Graphical abstract Editor, we provided image with high resolution. Please find it in a folder name "MIAC-D-18-00081" in the FTP site. A dual-mode (colorimetric-fluorometric) detection nanoplatform based on OPD-modified MoS2 nanosheets is used to quantitatively detect H2O2, cell numbers and intracellular H2O2. The MoS2 nanoprobes also permit sensitive fluorescence imaging of intracellular H2O2, and can discriminate intracellular oxide states in living cancerous and normal cells.

La(1-x)Bi(1+x)S3 (x ≈ 0.08): An n-Type Semiconductor.

The new bismuth chalcogenide La(0.92)Bi(1.08)S3 crystallizes in the monoclinic space group C2/m with a = 28.0447(19) Å, b = 4.0722(2) Å, c = 14.7350(9) Å, and ß = 118.493(5)°. The structure of La(0.92)Bi(1.08)S3 is built of NaCl-type Bi2S5 blocks and BiS4 and LaS5 infinitely long chains, forming a compact three-dimensional framework with parallel tunnels. Optical spectroscopy and resistivity measurements reveal a semiconducting behavior with a band gap of ∼1 eV and activation energy for transport of 0.36(1) eV. Thermopower measurements suggest the majority carriers of La(0.92)Bi(1.08)S3 are electrons. Heat capacity measurements indicate no phase transitions from 2 to 300 K. Band structure calculations at the density functional theory level confirm the semiconducting nature and the indirect gap of La(0.92)Bi(1.08)S3.

Highly efficient and ultrastable visible-light photocatalytic water splitting over ReS2.

Two dimensional materials have many outstanding intrinsic advantages that can be utilized to enhance the photocatalytic efficiency of water splitting. Herein, based on ab initio calculations, we reveal that for monolayer and multilayer rhenium disulphide (ReS2), the band gap and band edge positions are an excellent match with the water splitting energy levels. Moreover, the effective masses of the carriers are relatively light, and the optical absorption coefficients are high under visible illumination. Due to the feature of weak interlayer coupling, these properties are independent of the layer thickness. Our results suggest that ReS2 is a stable and efficient photocatalyst with potential applications in the use of solar energy for water splitting.

Molecular mechanisms of secretory autophagy and its potential role in diseases.

Autophagy is a cellular degradation system that recycles or degrades damaged organelles, viral particles, and aggregated proteins through the lysosomal pathway. Autophagy plays an indispensable role in cellular homeostasis and communication processes. An interesting aspect is that autophagy also mediates the secretion of cellular contents, a process known as secretory autophagy. Secretory autophagy differs from macroautophagy, which sequesters recruited proteins, organelles, or viral particles into autophagosomes and degrades these sequesters in lysosomes, while the secretory autophagy pathway participates in the extracellular export of cellular contents sequestered by autophagosomes through autophagy and endosomal modulators. Recent evidence reveals that secretory autophagy is pivotal in the occurrence and progression of diseases. In this review, we summarize the molecular mechanisms of secretory autophagy. Furthermore, we review the impact of secretory autophagy on diseases, including cancer, viral infectious diseases, neurodegenerative diseases, and cardiovascular diseases. Considering the pleiotropic actions of secretory autophagy on diseases, studying the mechanism of secretory autophagy may help to understand the relevant pathophysiological processes.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.