Target-Oriented Synthesis of Borate Derivatives Featuring Isolated [B3O3] Six-Membered Rings as Structural Features.

Borates provide an excellent platform for investigating the optical nonlinearity and linearity of crystals as photoelectric functional materials. In our work, borate derivatives with isolated [B3O3] six-membered rings as structural features are the preferred system due to their simple functional units and excellent properties. Herein, by utilizing the target-oriented synthesis, a series of borate derivatives, A2[B3O3F4(OH)] (A= NH4, Rb, Cs) (ABOFH), K2.3Cs0.7B3O3F6 (KCsBOF), and Cs3[B3O3(OH)3]Cl3 (CsBOHCl), with novel heteroanionic groups containing [BOxF4-x] (x = 0-3) and/or [BO2(OH)] units were obtained. ABOFH, KCsBOF, and CsBOHCl construct different two-dimensional pesudolayers featuring [B3O3F4(OH)], [B3O3F6], and [B3O3(OH)3] units, respectively. Also, the optical properties and the arrangement information of these anionic groups were studied. Among the total five compounds, (NH4)2[B3O3F4(OH)] and Cs3[B3O3(OH)3]Cl3 with enlarged birefringence and sufficient band gaps were screened out as promising birefringent crystals due to the optimally aligned configuration of birefringence-active heteroanionic units. The successful results of target-oriented synthesis indicate a more profound conclusion that the borate system now has more diversified structural chemistry, and an effective strategy was proposed to modify the arrangement and species of anionic units to optimize the performance of optical crystals.

The contribution of inner electron excitation to the electronic stopping power of palladium for protons.

The electronic stopping power of palladium (Pd) for protons is investigated based on time-dependent density functional theory combined with Ehrenfest molecular dynamics simulations. The electronic stopping power of Pd with explicitly considering inner electrons for protons is calculated and the excitation mechanism for the inner electrons of Pd is revealed. The velocity proportionality of the low-energy stopping power of Pd is reproduced. Our study verified that the inner electron excitation contributes significantly to the electronic stopping power of Pd in the high energy range, which is strongly dependent on the impact parameter. The electronic stopping power obtained from the off-channeling geometry is in quantitative agreement with the experimental data in a wide velocity range, and the discrepancy around the stopping maximum is further reduced by considering the relativistic correction on the binding energy of inner electrons. The velocity dependence of the mean steady-state charge of protons is quantified, and the results showed that the participation of 4p-electrons reduces the mean steady-state charge of protons, and consequently decreases the electronic stopping power of Pd in the low energy range.

From ß-Na2 B6 O10 to Na3 AlB8 O15 and Na3 Al2 B7 O15 : Structural Tuning of Anionic-Group Architectures by Substitution of [BO4 ] by [AlO4 ] Covalent Tetrahedra.

Two new sodium aluminum borates, Na3 AlB8 O15 and Na3 Al2 B7 O15 , have been successfully synthesized by the high-temperature solution method. They crystallize in the different space groups, P21 /c and P2/c, respectively. The B-O configurations of ß-Na2 B6 O10 , Na3 AlB8 O15 and Na3 Al2 B7 O15 are compared to feature complicated different dimensional open-framework structures caused by the substitution of [BO4 ] by [AlO4 ] covalent tetrahedra. Moreover, the experimental results indicate that Na3 AlB8 O15 and Na3 Al2 B7 O15 have short ultraviolet (UV) cutoff edges (<187 nm). The first-principles calculations show that Na3 AlB8 O15 and Na3 Al2 B7 O15 have moderate birefringence (0.075 and 0.041@1064 nm, respectively).

Rearrangement of [B2O5] Dimers within [B7O14] Clusters Enables Enhanced Optical Anisotropy in Li3Cs6Al2B14O28F.

Borates with tunable structure and property currently provide a new rich source for solid-state chemistry and materials science. Realization of property improvement via simple structural regulation is a rising hot spot of borate-based research. Herein, a new aluminoborate fluoride, Li3Cs6Al2B14O28F, with [B7O14] clusters was discovered, and it was found to melt congruently. The optimally aligned [B2O5] dimers within [B7O14] clusters make Li3Cs6Al2B14O28F an enhanced birefringence, which is about 4.3× higher than its congener compound Li4Cs3B7O14 with same [B7O14] clusters. Structural analysis and additional theoretical calculations have revealed the origin of enhanced optical anisotropy.

Rutin Promotes Pancreatic Cancer Cell Apoptosis by Upregulating miRNA-877-3p Expression.

(1) Background: pancreatic cancer is one of the most serious cancers due to its rapid and inevitable fatality, which has been proved very difficult to treat, compared with many other common cancers. Thus, developing an effective therapeutic strategy, especially searching for potential drugs, is the focus of current research. The exact mechanism of rutin in pancreatic cancer remains unknown. (2) Method: three pancreatic cancer cell lines were used to study the anti-pancreatic cancer effect of rutin. The potent anti-proliferative, anti-migration and pro-apoptotic properties of rutin were uncovered by cell viability, a wound-healing migration assay, and a cell apoptosis assay. High-throughput sequencing technology was used to detect the change of miRNAs expression. Immunoblotting analysis was used to detect the expression of apoptotic proteins. (3) Results: CCK-8 and EDU assays revealed that rutin significantly inhibited pancreatic cancer cells' proliferation (p < 0.05). A wound-healing assay showed that rutin significantly suppressed pancreatic cancer cells' migration (p < 0.05). A flow cytometric assay showed that rutin could promote pancreatic cancer cells' apoptosis. Intriguingly, rutin significantly upregulated miR-877-3p expression to repress the transcription of Bcl-2 and to induce pancreatic cancer cell apoptosis. Accordingly, rutin and miR-877-3p mimics could promote apoptotic protein expression. (4) Conclusions: our findings indicate that rutin plays an important role in anti-pancreatic cancer effects through a rutin-miR-877-3p-Bcl-2 axis and suggests a potential therapeutic strategy for pancreatic cancer.

Jiedutongluotiaogan formula restores pancreatic function by suppressing excessive autophagy and endoplasmic reticulum stress.

CONTEXT: Jiedutongluotiaogan formula (JTTF), a traditional Chinese medicine (TCM), could promote islet function. However, the potential effect of JTTF on endoplasmic reticulum stress (ERS) and autophagy have not been reported. OBJECTIVE: This study explores the potential effect of JTTF on ERS and autophagy in the pancreas. MATERIALS AND METHODS: The Zucker diabetic fatty (ZDF) rats were randomised into five groups, control, model, JTTF (1, 3, 5 g/kg/day for 12 weeks). LPS induced pancreatic ß-cells were treated with JTTF (50, 100, 200 µg/mL). LPS was used to induce pancreatic ß-cell injury, with cell viability and insulin secretion evaluated using MTT, glucose-stimulated insulin secretion (GSIS) assays, and PCR. Intracellular Ca2+ concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining. RESULTS: Compared with the model group, body weight, FGB, HbA1c, IPGTT, FINs, and HOMA-IR in JTTF treatment groups were significantly reduced. In islets cells treated with JTTF, the pancreatic islet cells in the JTTF group were increased, lipid droplets were reduced, and there was a decrease in Ca2+ (16.67%). After JTTF intervention, PERK, p-PERK, IRE1α, p- IRE1α, ATF6, eIF2α, GRP78, p-ULK1, LC3 and p62 expression decreased, whereas Beclin1and p-mTOR expression increased. In addition, the expression of proteins related to apoptosis in the JTTF groups were lower than those in the control group. DISCUSSION AND CONCLUSIONS: JTTF may alleviate pancreatic ß-cell injury by inhibiting ER stress and excessive autophagy in diabetic rats. This provides a new direction for treating diabetes and restoring pancreatic dysfunction by TCM.

Achieving Short-Wavelength Phase-Matching Second Harmonic Generation in Boron-Rich Borosulfate with Planar [BO3 ] Units.

Ultraviolet (UV) nonlinear optical (NLO) crystals which can produce short-wavelength lasers via a direct second harmonic generation (SHG) process are of great importance in modern laser technology. Currently, the exploration of UV NLO crystals in borosulfates is nearly stagnant since the non-phase matching (PM) property lies on the small birefringence induced by the intrinsically small optical anisotropy of the tetrahedral groups. Herein, for the first time, the planar [BO3 ] units were introduced into borosulfates leading to a boron-rich borosulfate (NH4 )2 B4 SO10 with unprecedented [B4 SO10 ]∞ layers and evidently enhanced birefringence. To the best of our knowledge, it achieves the shortest SHG PM wavelength of 252 nm in all reported borosulfates with deep UV cutoff edge (184 nm), large SHG response (1.1×KDP at 1064 nm and 0.15×ß-BBO at 532 nm) and large birefringence (0.053 at 1064 nm) and is easy to grow single crystals via simple chemical vapor deposition method. These results confirm the feasibility of utilizing planar [BO3 ] units to optimize birefringence of borosulfates, and also open up broad prospects for UV NLO crystals in boron-rich borosulfates.

Inhibitory effect of bushen huoxue formula against dehydroepiandrosterone-induced inflammation in granulosa cells through TLR4/NF-κB signaling pathway.

Androgen exposure may be an important factor in promoting the development of polycystic ovary syndrome (PCOS) and disease progression. Bushen Huoxue Formula (BHF), a traditional Chinese medicine, is prescribed in clinical settings as a PCOS remedy, albeit with unclear pharmacological effects on granulosa cells. The present research explores potentially advantageous BHF impacts and whereby BHF alleviates dehydroepiandrosterone (DHEA)-induced inflammation and endocrine disruption. Six chemical components in BHF were identified and fingerprint analysis showed good reproducibility. Using a human granulosa cell line (KGN), BHF effects on cell viability, secretion of steroidogenic and inflammatory factors were evaluated and TLR4/NF-κB pathway expression was examined. Our results demonstrate that BHF treatment of KGN cells in a DHEA-induced inflammatory state led to increased cell viability, decreased testosterone and estradiol production, and decreased CYP19A1 and HSD3B2 mRNA expression. Further experiments revealed that BHF inhibited the expression of pro-inflammatory cytokines and considerably hindered up-regulation in protein levels of TLR4, MyD88, and TRAF6, while inhibiting the activation of NF-κB and phosphorylation of IκBα. Collectively, BHF administration protected granulosa cells from DHEA-induced injuries through down-regulating pro-inflammatory cytokines and blocking the pathway of TLR4/NF-κB. Therefore, BHF hold promise as a therapeutic formulation for preventing androgen induced PCOS.

Cation Substitution of Hexagonal Triple Perovskites: A Case in Trimetallic Tellurates A2A'BTe2O9.

Three new tellurates, namely, K2BaPb0.62Ba0.38Te2O9 (1), Rb2BaPb0.7Ba0.3Te2O9 (2), and Ba2KLiTe2O9 (3), with hexagonal triple-perovskite structures have been designed via a cation substitution strategy. All three centrosymmetric compounds crystallize in the same hexagonal space group P63/mmc. In their structures, the [BTe2O9] (B = Pb/Ba for 1 and 2 and Li for 3) groups construct the final three-dimensional framework using face-sharing [Te2O9] dimmers and vertex-linked [BO6] linkages. Meanwhile, the theoretical calculations demonstrate the numerical differences of their birefringence. Thermal stability analysis and differential scanning calorimetry were performed, and UV-vis-NIR diffuse reflectance spectra and infrared spectra of the three title compounds were also characterized and analyzed.

Cs3B3O3F6 with a Deep-Ultraviolet Cutoff Edge and a Suitable Birefringence as the Potential Zero-Order Waveplate Material.

The zero-order waveplates, the essential materials in altering the polarization state of optical waves, are significant in polarimetry and the laser industry. Restricted by birefringence and absorption edge, few materials can have moderately small birefringence (Δn < 0.01) and a deep-ultraviolet (DUV; λ < 200 nm) transparency range. We used the B3O3F6 unit for designing the zero-order waveplate material, which is composed of three BO2F2 tetrahedra interconnected by corner sharing. Here we obtained a new Cs3B3O3F6 compound with the isolated B3O3F6 unit by a high-temperature solution method, which has the DUV cutoff edge and suitable birefringence (0.0069 at 532 nm) based on the experimental and computational results. This demonstrates that the isolated B3O3F6 unit is a potential group, which favors the search for suitable compounds for DUV zero-order waveplate materials.

Inhibition of endoplasmic reticulum stress and excessive autophagy by Jiedu Tongluo Tiaogan Formula via a CaMKKß/AMPK pathway contributes to protect pancreatic ß-cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of ß cells. AIM OF THE STUDY: We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used. MATERIALS AND METHODS: The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 µg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining. RESULT: 28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic ß-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKß/AMPK pathway. CONCLUSIONS: The present study findings show that JTTF may protects ß-cells by inhibiting the CaMKKß/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM.

New insights into ginsenoside Rg1 regulating the niche to inhibit age-induced germline stem cells depletion through targeting ECR/BMP signaling pathway in Drosophila.

PURPOSE: The age-induced imbalance in ecological niches leads to the loss of GSCs, which is the main reason for ovarian germline senescence. Ginsenoside Rg1 can delay ovarian senescence. Here, we shed light on new insights of ginsenoside Rg1 in regulating the niche to maintain GSCs self-renewal and discussing related molecular mechanisms. METHODS: The differences among GSC number, reproductive capacity of naturally aging female Drosophila after ginsenoside Rg1 feeding were analyzed by immunofluorescence and behavior monitoring. The expressions of the active factors in the niche and the BMP signaling were analyzed through Western blot and RT-qPCR. The target effect was verified in the ECR mutant and combined with the molecular docking. RESULTS: Ginsenoside Rg1 inhibited the age-induced reduction of the GSCs number and restored offspring production and development. Ginsenoside Rg1 promoted the expression of anchor proteins E-cadherin, stemness maintenance factor Nos and differentiation promoting factor Bam, thereby GSCs niche homeostasis was regulated. In addition, ginsenoside Rg1 was bound to the LBD region of the hormone receptor ECR. Ginsenoside Rg1 promotes the regeneration of GSCs by targeting the ECR to increase pSmad1/5/8 expression and thereby activating the BMP signaling pathway. In addition, ginsenoside Rg1 maintenance of niche homeostasis to promote GSCs regeneration is dependent on ECR as demonstrated in ECR mutants. CONCLUSIONS: Ginsenoside Rg1 regulated the ecological niche homeostasis of GSCs and promoted the regeneration of GSCs by targeting the ECR/BMP signaling pathway in hormone-deficient states in aging ovaries. It is of great significance for prolonging fertility potential and delaying ovarian senescence.

Inhibitory effect of phellodendrine on C48/80-induced allergic reaction in vitro and in vivo.

The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that can prevent or treat allergic diseases. Phellodendron amurense Rupr. has long been applied as a treatment for allergic diseases, whose primary component is phellodendrine. However, the efficacy of phellodendrine as a treatment for allergic diseases remains to be assessed. Mast cells are the primary effectors of allergic reactions, which are not only activated by IgE-dependent pathway, but also by IgE-independent pathways via human MRGPRX2, rat counterpart MRGPRB3. As such, this study explored the effect and mechanism of phellodendrine through this family receptors in treating allergic diseases in vitro and in vivo. These analyses revealed that phellodendrine administration was sufficient to protect against C48/80-induced foot swelling and Evans blue exudation in mice, and suppressed C48/80-induced RBL-2H3 rat basophilic leukemia cells degranulation, and ß-HEX, HIS, IL-4, and TNF-α release. Moreover, phellodendrine could reduce the mRNA expression of MRGPRB3 and responsiveness of MRGPRX2 by altering its structure. It was able to decrease Ca2+ levels, phosphorylation levels of CaMK, PLCß1, PKC, ERK, JNK, p38, and p65, and inhibit the degradation of IκB-α. These analyses indicate that berberine inhibits the activation of PLC and downregulates the release of Ca2+ in the endoplasmic reticulum by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequently inhibiting downstream MAPK and NF-κB signaling, ultimately suppressing allergic reactions. There may thus be further value in studies focused on developing phellodendrine as a novel anti-allergic drug.

A Cation-Driven Approach toward Deep-Ultraviolet Nonlinear Optical Materials.

The design of new materials with special performances is still a great challenge, especially for the deep-ultraviolet nonlinear optical materials in which it is difficult to balance large bandgaps and strong second harmonic generation responses due to their inverse relationship. Cation variation not only influences the whole structure frameworks but also directly participates in the formation of electronic structures, both of which could lead to the uncontrollability of the properties of the designed materials. Here, a novel approach, aiming at purposeful and foreseeable material designs, is proposed to characterize the role of cations. By the verification of several series of borates, the influences of cation variation on property changes are explored systematically. Accordingly, a feasible strategy of designing deep-ultraviolet nonlinear optical materials by substituting barium for lead has been concluded, which could obviously blue-shift the ultraviolet cutoff edge and maintain the relatively strong second harmonic generation response (more than 2 times of KH2PO4), achieving the property optimization, and especially works efficiently in fluorooxoborates. The property optimization design strategy and the cation characterization method are not only helpful in exploring nonlinear optical materials but also enlightening in material design and selection.

Traditional Chinese Medicine in the treatment of hemorrhoids-a review of preparations used and their mechanism of action.

Hemorrhoids are a proctological disease primarily characterized by bleeding, prolapse, edema, and pain, severely affecting the quality of life. Surgery is an effective treatment for hemorrhoids, but the cost is relatively high, and complications such as difficulty in defecation, persistent pain, and heavy bleeding may occur postoperatively. Traditional Chinese Medicine (TCM) has a distinctive advantage in alleviating the clinical symptoms of hemorrhoid patients, reducing pain, and improving the quality of life. However, there are few summary literature about the mechanism of TCM in the prevention and treatment of hemorrhoids. Based on the etiology of hemorrhoids in both traditional Chinese and Western medicine, this paper reviews the recent research on the mechanism of TCM in the treatment of hemorrhoids, hoping to provide a basis for the better application of TCM in clinical and experimental research.

Large optical anisotropy-oriented construction of a carbonate-nitrate chloride compound as a potential ultraviolet birefringent material.

The design of new birefringent materials is very significant owing to their indispensable role in modulating the polarization of light and is vital in laser technology. Herein, by applying a large optical anisotropy-oriented construction induced by a synergy effect of multiple anionic groups, a promising carbonate-nitrate chloride, Na3Rb6(CO3)3(NO3)2Cl·(H2O)6, has been designed and synthesized successfully by the solvent evaporation method and single crystals of centimeter size were obtained by the recrystallization method in aqueous solution. It crystallizes in the hexagonal P63/mcm space group, the RbO9Cl polyhedra and the NaO7 polyhedra construct a three-dimensional (3D) framework by sharing O or Cl atoms and trigonal plane units (CO3 and NO3). The transmittance spectrum based on a 1 mm thick single-crystal plate shows that its short UV cut-off edge is about 231 nm. And the refractive index differences (0.14 @ 546 nm) measured by using a polarizing microscope on the (101) crystal plane, proves that Na3Rb6(CO3)3(NO3)2Cl·(H2O)6 has a large birefringence, which has potential application in the solar blind ultraviolet region. The theoretical calculations reveal that the π-conjugated CO3 and NO3 groups are the main cause of the birefringence. It demonstrates that combining π-conjugated CO3 and NO3 groups in one structure is an extremely effective strategy to explore new UV birefringent crystals.

Exploring Short-Wavelength Phase-Matching Nonlinear Optical Crystals by Employing KBe2BO3F2 as the Template.

Exploration of nonlinear optical (NLO) crystals that are competent in generating short-wavelength ultraviolet (UV, λ ≤ 266 nm, and even deep-UV, λ ≤ 200 nm) coherent light output by direct second harmonic generation (SHG) remains a formidable challenge. Herein, four UV/deep-UV NLO crystals, M2B4SO10 (M = K, Rb, and Cs) and Rb3B11PO19F3, were successfully synthesized by evolving the KBe2BO3F2 (KBBF) structure into mixed-anionic borosulfate and fluoroborophosphate systems. They display functional [B4SO10]∞ or [B11PO19F3]∞ KBBF-type layers that are composed of [BO3], [BO4], and [SO4] groups or [BO3], [BO4], [BO3F], and [PO4] groups, respectively. Experimental characterization and numerical computation results indicate that these crystals possess exceptional NLO performance, including large SHG responses (0.9-1.7 × KDP at 1064 nm and 0.1-0.3 × ß-BBO at 532 nm) and adequate birefringence to fulfill the SHG phase-matching (PM) condition at 266 nm. In particular, the shortest type-I PM wavelength (λPM) of Rb3B11PO19F3 reaches 180 nm, which implies that Rb3B11PO19F3 can become a prospective deep-UV NLO crystal. In addition, single crystals of K2B4SO10, Rb2B4SO10, and Cs2B4SO10 are easily obtained by the high-temperature solution approach. This work will facilitate the discovery of short-wavelength PM NLO crystals by using the KBBF structure as the template.

An excellent deep-ultraviolet birefringent material based on [BO2]∞ infinite chains.

Birefringent materials play indispensable roles in modulating the polarization of light and are vital in the laser science and technology. Currently, the design of birefringent materials operating in the deep-ultraviolet region (DUV, λ ≤200 nm) is still a great challenge. In this work, we developed a new DUV birefringent crystal LiBO2 based on [BO2]∞ infinite chains in the Li-B-O system, which simultaneously achieves the shortest UV cutoff edge (164 nm) and the largest birefringence (≥0.168 at 266 nm) among all the reported borate-based DUV birefringent materials. Single crystals of LiBO2 with dimensions up to Ø55 × 34 mm3 were grown by the Czochralski method, providing access to large-sized single crystal with low cost. Moreover, it has a high laser damage threshold and stable physicochemical properties. These outstanding characters unambiguously support that LiBO2 can be an excellent birefringent material for DUV application.

Polydatin prevents lipotoxicity-induced dysfunction in pancreatic ß-cells by inhibiting endoplasmic reticulum stress and excessive autophagy.

BACKGROUND: Chronically elevated free fatty acid levels can adversely affect pancreatic ß-cells, leading to insulin resistance and eventually type 2 diabetes mellitus (T2DM). Polydatin (PD) from Polygonum cuspidatum has been shown to regulate blood lipid content and lower cholesterol levels. However, there have been no reports on the potential therapeutic effects and actions of PD on lipotoxicity in ß-cells. PURPOSE: This study aimed to investigate the protective effects of PD on palmitate (PA)-treated INS-1 insulinoma cells and diabetic mice. METHODS: Cells were incubated with PA and varying concentrations of PD for 24 h. Viability assays, morphological observations, flow cytometric analysis, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to assess the effects of PD on PA-induced lipotoxicity. Western blotting was used to measure the endoplasmic reticulum stress (ERS) and the levels of autophagy-related factors after incubation with inducers and inhibitors of ERS and autophagy. Diabetic mice were treated with intragastric PD for 6 weeks followed by the measurement of their physiological and blood lipid indices and assessment of the results of histological and immunofluorescence analyses. RESULTS: Treatment with PD after PA exposure enhanced insulin secretion and the expression of diabetes-associated genes. PD promoted ß-cell function by reducing the levels of proteins associated with ERS and autophagy while also attenuating ERS triggered by tunicamycin. PD also reduced tunicamycin-induced autophagy, indicating that it regulated ERS-mediated autophagy and reduced PA-induced cellular dysfunction. In addition, treatment of db/db mice with PD substantially reduced body weight gain, alleviated dyslipidemia, improved ß-cell function, and reduced insulin resistance. CONCLUSION: These results suggest that PD protects ß-cells from lipotoxicity-induced dysfunction and apoptosis by inhibiting ERS and preventing excessive autophagy. Our study provides a new basis for exploring the potential of PD against ß-cell lipotoxicity and T2DM.

Ginsenoside Rf inhibits human tau proteotoxicity and causes specific LncRNA, miRNA and mRNA expression changes in Caenorhabditis elegans model of tauopathy.

Under pathological conditions, human tau (htau) hyperphosphorylation promotes formation of proteotoxic intracellular amyloid aggregates that may underlie neurodegenerative diseases known as tauopathies, prompting researchers to develop treatments that inhibit htau aggregation as a promising therapeutic strategy. Ginsenosides, the main active constituents of Panax ginseng C. A. Meyer (ginseng), appear to inhibit tau aggregation and disassociation in tauopathy models, although their active components and molecular mechanisms are unknown. Here, we used a novel Caenorhabditis elegans (C. elegans) tauopathy model to identify ginsenoside monomers which may repress htau proteotoxicity. Our findings indicated that ginsenoside Rf prevented tau aggregation and reversed abnormal tau aggregation-induced phenotypes and alleviated neurodegeneration in worms. Notably, deep RNA-seq analysis of ginsenoside Rf-treated and untreated worms with tauopathy revealed that ginsenoside Rf altered expression levels of 24 up- and 36 down-regulated lncRNA transcripts, 32 up- and 22 down-regulated miRNAs and 65 up- and 30 down-regulated mRNA transcripts. Based on GO and KEGG pathway annotation analyses, identified mRNAs, miRNAs and lncRNAs-associated gene targets were functionally related to neuron-related terms (e.g., neuron development, axon and motor neuron axon guidance) and longevity regulating pathways. Importantly, RT-qRCR results suggested that 6 miRNAs (miR-786, miR-2208b, miR-34, miR-241, miR-247 and miR-4805), 8 lncRNAs (MSTRG.20812.2, MSTRG.22617.2, MSTRG.28210.13, MSTRG.5728.12, MSTRG.29708.1, MSTRG.3342.25, MSTRG.3342.31 and MSTRG.8841.8) and 7 mRNAs (nas-33, math-28, T14B4.19, col-17, rol-6, sqt-1 and irg-4) were potential targets of ginsenoside Rf inhibition of tauopathy. These results partially explain mechanisms underlying ginsenoside Rf-associated alleviation of htau proteotoxicity and will guide future strategies to discover potential therapeutic targets for preventing and alleviating tauopathies.