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Rituximab (RTX) has been the first option in idiopathic membranous nephropathy (IMN). However, the clinical effect was not very satisfactory. This study aimed to explore the clinical efficacy and safety of the combination of RTX and glucocorticoids (GC) in anti-phospholipase A2 receptor (anti-PLA2R) antibody positive IMN. Sixty-six patients were randomly divided into RTX/GC group (RTX infusion plus short-term oral GC) and RTX group (RTX infusion alone) in this prospective cohort study. Complete remission (CR) and partial remission (PR) were the primary outcomes. Adverse events were the secondary outcomes. The laboratory index including serum albumin, 24 h urinary protein, serum creatinine, estimated glomerular filtration rate, and anti-PLA2R antibody titer were also monitored. All patients were followed for at least 12 months. During the 12-month follow-up, the composite remission rates in RTX/GC and RTX groups were 74.3% and 67.7%, and the CR rates were 34.3% and 19.4%, respectively. The median time of remission in RTX/GC group was shorter than the RTX group (P < 0.001). Compared with RTX monotherapy, the combination of RTX and GC significantly decreased the anti-PLA2R antibody titer (P = 0.028). No significant difference was observed in the incidence of adverse events. The results of the Kaplan–Meier survival analysis indicated that the cumulative CR rate and cumulative composite remission rate in RTX/GC group were all better than the RTX group (P = 0.043, P = 0.040, respectively). The combination of RTX and GC was better than RTX monotherapy without increasing the adverse events in the treatment of IMN. [ABSTRACT FROM AUTHOR]

A GO (graphene oxide)/ZnO/Cu2O antibacterial coating was successfully sprayed on the ultrafine glass fibers using room temperature hydrothermal synthesis and air spraying techniques. The microstructures of the antibacterial coating were characterized, and the results showed that the Cu2ONPs (nano particles)/ZnONPs were uniformly dispersed on the surface of GO. Then, the antibacterial properties of the GO/ZnO/Cu2O (GZC) antibacterial coating were evaluated using the disc diffusion test. It was found that the coating exhibits excellent antibacterial properties and stability against E. coli and S. aureus, and the antibacterial rate of each group of antibacterial powder against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was 100%. To explore the antibacterial mechanism of the GZC antibacterial powder on the ultrafine glass fibers based on the photocatalysis/oxidative stress method, the photoelectric coupling synergistic effect between GZC antibacterial coating was analyzed deeply. The results all showed that the photochemical activity of GZC antibacterial powder was significantly improved compared with pure component materials. The enhancement of its photochemical activity is beneficial to the generation of ROS (including hydroxyl radicals, superoxide anion radicals, etc.), which further confirms the speculation of the photocatalytic/oxidative stress mechanism. [ABSTRACT FROM AUTHOR]

As aging increases, monoclonal gammopathy is becoming more common and monoclonal gammopathy of renal significance (MGRS) is gaining attention due to frequent renal involvement. Within MGRS, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a special category. The disease was first described in 2004 and the research history on it is relatively short. Compared with other MGRS, the detection rate of circulating clones is lower in patients with PGNMID, which is easy to miss and misdiagnose in clinical work. In this review, the etiology and clinical features of PGNMID are discussed. It is noted that PGNMID is associated not only with MGRS, but also with malignancy, infection and other factors. PGNMID is not a disease exclusive to the elderly—young people can also develop this disease. Due to the low detection rate of circulating clones in most patients, confirmation of the disease needs to be combined with renal pathology, which emphasizes the importance of completing light and heavy chain subtype staining. Treatment options for patients with PGNMID differ by etiology. For MGRS-associated PGNMID, the current treatment is primarily empirical and more research evidence is needed to fill the treatment gap. [ABSTRACT FROM AUTHOR]

This paper is devoted to the finite‐time local piecewise control for parabolic partial differential equations (PDEs) by using dynamic output feedback control strategy, where the controller is designed as an ordinary differential equation (ODE). This makes the closed‐loop system PDE‐ODE coupled, which is employed to accurately describe the dynamics of the PDE system. According to the constructed PDE‐ODE coupled model, a local piecewise dynamic feedback control law is first proposed. Sufficient conditions on finite‐time stabilisation of the parabolic PDE‐ODE coupled system by the suggested feedback controller are then developed in the sense of both complete spatial measurement and incomplete spatial measurement of the observed output of the PDE system, respectively. Finally, the issues regarding the finite‐time stabilisation of the closed‐loop system is converted into the feasibility of matrix inequalities, and some simulation studies are provided to verify the effectiveness of the proposed results. [ABSTRACT FROM AUTHOR]

Background: N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. However, its functions in diabetic nephropathy (DN) have not been determined. Here, we investigated the role of METTL14, a key component of the m6A methyltransferase complex, in DN. Methods: The expression of METTL14 was detected in DN patients and human renal glomerular endothelial cells (HRGECs). In vitro and in vivo experiments were performed to explore the functions of METTL14 on high glocse-induced HRGECs and renal injury of DN mice. We also investigated whether METTL14 works by regulating α-klotho expression through m6A modification. Results: METTL14 were highly expressed in kidneys of DN patients and high glocse-induced HRGECs both at the mRNA and protein level. Overexpression of METTL14 increased ROS, TNF-α and IL-6 levels and apoptosis in HRGECs. Conversely, METTL14 silence decreased the levels of ROS, TNF-α and IL-6 and cell apoptosis. We confirmed that METTL14 down-regulated α-klotho expression in an m6A-dependent manner. In addition, we also found that METTL14 aggravated renal injury and inflammation of db/db mice, which could partially rescued by α-klotho. Conclusion: Our data revealed that METTL14 plays a vital role in high glucose-induced glomerular endothelial cells and diabetic nephropathy through m6A modification of α-klotho. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to explore the relative efficacy and safety of different tacrolimus (TAC) concentrations in the treatment of patients with idiopathic membranous nephropathy (IMN). A total of 260 IMN patients with nephrotic syndrome (NS) were recruited. Among these, 125 patients had TAC concentrations no greater than 5 ng/ml (CTAC ≤ 5 ng/ml), and 135 patients had TAC concentrations greater than 5 ng/ml (CTAC > 5 ng/ml). The primary outcomes included complete remission (CR) rates and overall (OR) response rates. The secondary outcomes included 24-h urinary protein (24-h UP), serum albumin and serum creatinine, and adverse events (AEs). During the 12-month follow-up, the overall response rates were significantly different between the CTAC ≤ 5 ng/ml group and the CTAC > 5 ng/ml group (P < 0.0001). However, there was no significant difference in the CR at 12 months between the two groups (chi-square, 62% vs 63%, P = 0.852). Compared with the CTAC ≤ 5 ng/ml group, the CTAC > 5 ng/ml group had improved levels of 24 h UP (P = 0.017) and serum albumin (P = 0.010). Moreover, the incidences of acute reversible nephrotoxicity (P < 0.001), hepatotoxicity (P = 0.036), new-onset diabetes mellitus (P = 0.036), and glucose intolerance (P = 0.005) were lower in the CTAC ≤ 5 ng/ml group than in the CTAC > 5 ng/ml group. The CTAC > 5 ng/ml group was improved relative to the CTAC ≤ 5 ng/ml group in terms of a PR and CR at 6 months, but there was no difference in the CR between the two groups at 12 months. [ABSTRACT FROM AUTHOR]

In this paper, the finite-time bounded control problem for coupled parabolic PDE-ODE systems subject to time-varying boundary disturbances and to time-invariant boundary disturbances is considered. First, the concept of finite-time boundedness is extended to coupled parabolic PDE-ODE systems. A Neumann boundary feedback controller is then designed in terms of the state variables. By applying the Lyapunov-like functional method, sufficient conditions which ensure the finite-time boundedness of closed-loop systems in the presence of time-varying boundary disturbances and time-invariant boundary disturbances are provided, respectively. Finally, the issues regarding the finite-time boundedness of coupled parabolic PDE-ODE systems are converted into the feasibility of linear matrix inequalities (LMIs), and the effectiveness of the proposed results is validated with two numerical simulations. [ABSTRACT FROM AUTHOR]

In this study, the finite‐time stabilisation problem of distributed parameter systems with control acting on a Dirichlet condition (DC) boundary is considered. First, the corresponding distributed parameter system with inhomogeneous DC‐boundaries is equivalently transformed into another distributed parameter system with homogeneous DC‐boundaries. A DC‐boundary feedback controller is then designed in terms of the distributed state, and sufficient conditions for L2 finite‐time stabilisation and W1,2 finite‐time stabilisation of distributed parameter systems are provided through the use of Lyapunov functionals. The issues regarding the finite‐time stabilisation of distributed parameter systems are converted into the feasibility of matrix inequalities, and the availability of the proposed results is verified through two numerical simulations. [ABSTRACT FROM AUTHOR]

Mixed μ -azido-Schiff-base palladacycles [Pd{ C , N - κ 2 -(4-R)C 6 H 3 CH = N-C 6 H 3 -2,6- i -Pr 2 }( μ 2 -N 3 )] 2 (R = H, 1 ; OMe, 2 ) served as a metal-template for the synthesis of unusual dicarbodiimido bridged complexes [( μ 2 -NCN-Xyl)Pd{ C , N - κ 2 -(4-R)C 6 H 3 CH = NC 6 H 3 -2,6- i -Pr 2 }] 2 (R = H; OMe) and mixed tetrazolato-isocyanido complexes [Pd( C , N - κ 2 -(4-R)C 6 H 3 CH = NC 6 H 3 -2,6- i -Pr 2 )(CN 4 -Xyl)(CN-Xyl)] (R = H; OMe). Reactions of ethyl isothiocyanate with 1 and 2 gave the ditetrazole-thiolato bridged Pd complexes [( μ 2 -SCN 4 -C 2 H 5 )Pd( C , N - κ 2 -(4-R)C 6 H 3 CH = NC 6 H 3 -2,6- i -Pr 2 )] 2 . All these complexes were fully characterized by FT-IR, NMR spectroscopy, elemental analysis and/or X-ray crystallography. [ABSTRACT FROM AUTHOR]

Correction to: METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of -klotho 2 METTL14 promoted high glucose-induced glomerular endothelial cell injury. Reference 1 Li M, Deng L, Xu G. METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of -klotho. [Extracted from the article]

Abstract: As previously reported [Popelar, J., Groh, D., Pelanova, J., Canlon, B., Syka, J., 2006. Age-related changes in cochlear and brainstem auditory functions in Fischer 344 rats. Neurobiol. Aging 27, 490–500; Buckiova, D., Popelar, J., Syka, J., 2007. Aging cochleas in the F344 rat: morphological and functional changes. Exp. Gerontol. 42, 629–638; Bielefeld, E.C., Coling, D., Chen, G.D., Li, M.N., Tanaka, C., Hu, B.H., Henderson, D., 2008. Age-related hearing loss in the Fischer 344/NHsd rat substrain. Hear. Res. 241, 26–33], aged Fischer 344 (F344) rats with severe hearing loss retain many outer hair cells (OHCs) especially in the middle turn of the cochlea. The current study confirmed the previous findings showing that aged OHCs were present, but dysfunctional. Distortion product otoacoustic emissions (DPOAE), which are believed to reflect in vivo OHC motility, were absent in the aged rats while the majority of OHCs (>80%) were present and morphologically intact. There was no detectable injury of OHC stereocilia as assessed by actin-staining and examination under the light microscope. Cochlear microphonics (CM) at 12kHz, recorded from the middle turn, only showed a slight age-related reduction, indicating a normal mechanoelectrical transduction apparatus in the remaining OHCs in the cochlear regions with 10–20% OHC loss. Activities of succinate dehydrogenase (SDH), an enzyme shared by the citric acid cycle and the mitochondrial electron transport chain (METC), were also at normal levels in aged OHCs. Importantly, aged OHCs showed reduced levels of prestin immunolabeling compared to young controls. Together with our previous finding showing that the stria vascularis and endocochlear potential were essentially normal in aged F344 rats [Bielefeld, E.C., Coling, D., Chen, G.D., Li, M.N., Tanaka, C., Hu, B.H., Henderson, D., 2008. Age-related hearing loss in the Fischer 344/NHsd rat substrain. Hear. Res. 241, 26–33], the results suggest that disruption of prestin is the major cause of DPOAE loss and loss of cochlear sensitivity. [Copyright &y& Elsevier]

This work presents the pore defects repair of additively manufactured chopped carbon fibre reinforced silicon carbide (CCF/SiC) composites using a combination of chemical vapour deposition (with methyltrichlorosilane and hydrogen as the precursor material) and reactive melt infiltration. The in-situ generation of silicon carbide nanowires (SiC nws) in the CCF/SiC composites significantly reduced the initial pore defects size, while the secondary SiC and free Si filled and closed the pore defects. The X-CT shows that the CCF/SiC composite after pore defects repair was internally dense and no significant pore geometry was observed. The incorporation of micron-sized CCF and nano-sized SiC nws as reinforcing phases resulted in a synergistic toughening effect. Specifically, the CCF enhances toughness through fibre debonding and pull-out mechanisms, while the SiC nws contribute to toughening through nanowire bridging and pull-out mechanisms. This dual toughening mechanism significantly improved bending strength from 210.7 to 274.5 MPa and elevated the fracture toughness from 3.2 to 3.6 MPa m1/2. Another notable advantage of the SiC nws is their ability to form a space network and reduce the thermal expansion coefficient. Consequently, this novel microstructural pore defects repair approach further enhanced the overall performance and reliability of the CCF/SiC composites based on additive manufacturing. This innovative approach holds great promise for the development of high-performance complex-structure CCF/SiC composites with wide-ranging applications across various industries. [ABSTRACT FROM AUTHOR]

As promising candidates for widespread application, advanced ceramic fiber mats with robust mechanical properties are urgently needed. However, the brittleness, fatigue failure, and large density of ceramic fiber pose significant obstacles to its practical application. Herein, a novel SiO2 aerogel/ZrO2 composite nanofibrous membrane (SZCNFM) with excellent flexibility was prepared by introducing SiO2 aerogel nanoparticles into ZrO2 nanofiber via simple co‐electrospinning. The developed tetragonal zirconia phase without changing up to 1200°C endows SZCNFM material with excellent thermal stability. Furthermore, the as‐prepared membranes exhibit fatigue resistance ability which can maintain 98% of the original stress after 100 buckling cycle tests. The addition of mesoporous structure aerogel reduces the heat transfer of the nanofibrous membrane, giving its low thermal conductivity (30 mW/m/K) and low‐frequency sound absorption (noise reduction coefficient of 0.52). Combined with the high‐temperature resistance, low thermal conductivity and excellent sound‐absorption ability make it a promising material for heat insulation and acoustic absorption. [ABSTRACT FROM AUTHOR]

A pinanamine‐based analog, (1R,2R,3R,5S)‐N‐((3‐cyclopropylthiophen‐2‐yl)methyl)‐2,6,6‐trimethylbicyclo[3.1.1]heptan‐3‐amine (M090) was synthesized and demonstrated with anti‐influenza activity to overcome the multi‐drug resistance. Herein, a rapid and robust liquid chromatography‐tandem mass spectrometry method was developed and validated to quantify M090 in rat plasma. With simple protein precipitation by methanol, the separation of M090 was performed on a Waters BEH‐C18 column (2.1 × 100 mm, 1.7 μm) by gradient elution at 0.4 mL/min with mobile phases consisting of water containing 0.1 % formic acid (phase A) and methanol (phase B). M090 and clenbuterol (internal standard) were detected using multiple reaction monitoring in positive electrospray ionization mode with transitions of m/z 290.3→137.0 and m/z 277.0→203.0, respectively. The method was validated over a linear range of 1.0–2400 ng/mL with a regression coefficient of 0.9974 and no endogenous interference. The intra‐ and inter‐batch precisions were within 8.29% and accuracy ranged from 100.3% to 108.1% for M090. The validated method was utilized to evaluate the in vitro metabolic stability and in vivo pharmacokinetics of M090 in rats. [ABSTRACT FROM AUTHOR]

Diabetes is the result of having an inadequate supply of functional insulin-producing β-cells. Efforts in research and development that focused on using systemic pathway to induce β-cell regeneration have had limited clinical success. Emerging studies implicate local islet molecular and cellular factors in pancreatic β-cell homeostasis. Intraislet endothelial cells (IECs), a key ally of pancreatic β-cells, secrete factors that could affect β-cell survival and insulin production. Fibroblast growth factor (FGF) 21 is an endocrine hormone that regulates energy homeostasis and insulin sensitivity. The function of endogenous FGF-21 derived from ECs is undefined in diabetes. With a loss-of-function approach, this study sought to determine the role of EC-FGF-21 in pancreatic β-cell homeostasis in STZ-induced diabetic mice and high-fat diet (HFD)-induced obese mice. Mice with EC-specific deletion of FGF-21 gene (EC-FKO) were generated by crossing Tie2-Cre mice with FGF-21loxP mice. In 8-to-10-week-old male mice (n=15/group) treated with STZ (50 mg/kg, i.p. for consecutive 5d and killed 4 weeks later), EC-FKO vs. wild type C57BL/6J (WT) mice displayed more severe hyperglycemia, degeneration of insulin-producing β-cells, and expansion of glucagon-producing α-cells. Both groups showed similar changes in pancreatic Glut2 and PARP1 protein levels and vascular density. In 8-to-10-week-old WT male mice (n=15/group) fed an HFD (TestDiet: 60% energy from fat) for 16 weeks, obesity and insulin resistance developed, along with lipid accumulation in the islet and compensatory expansion of β-cell mass, all of which were worsened, except for less β-cell mass expansion, in EC-FKO mice. Our latest immunofluorescent data showed a significant reduction of IEC-FGF-21 protein staining in WT mice treated with STZ or HFD vs. non-treated mice. Our findings suggest that EC-FGF-21 is required to maintain β-cell homeostasis under stress conditions. Loss of IEC-FGF-21 may contribute, at least in part, to β-cell degeneration in diabetes. Disclosure: M. Li: None. M. Qian: None. J. Xu: None. Funding: National Institutes of Health [ABSTRACT FROM AUTHOR]

Ceramic nanofibrous aerogels have attracted great interest because of their extraordinary multifunctional properties. Herein, a facile strategy was proposed to create SiO 2 nanofibers-BN nanoribbons assembled binary aerogel with excellent temperature-invariant super-flexibility, as well as low thermal conductivity, low infrared radiation and excellent sound absorption properties. In addition, the unique structure of the nanofibers-nanoribbon aerogel acts as the thermal insulation layer, combined with Al foil acting as an infrared reflection layer, forming a component that can effectively hide high infrared targets. The nanofibrous-nanoribbons binary aerogel possess low thermal conductivity (0.0288 W/(m⋅K)) and outstanding sound-absorption ability (NRC value of 0.43), as well as excellent infrared stealth ability, which makes it an ideal candidate for thermal insulation and sound absorption in multi fields. [ABSTRACT FROM AUTHOR]

In this work, an environmentally friendly, superhydrophobic and durable modified melamine sponge was fabricated through a simple two-step dipping method. Through this strategy, the active carbon (AC) particles and reduced graphene oxide (rGO) were fixed on the melamine sponge skeleton with polydimethylsiloxane (PDMS) glue to form MS/rGO/AC/PDMS sponge, which has a multi-stage pore structure. Water contact angle (WCA) revealed that the as-prepared sponge possessed excellent water repellency up to 164°. Being applied in the field of oil/water separation, MS/rGO/AC/PDMS exhibited excellent oil-water selectivity, high oil sorption ability up to 120 g/g, and separation efficiency of over 99.85%. It is worth noting that under complex environments such as acid-base, fatigue and abrasion, the obtained sponge can maintain original properties, and the water contact angle exceeds 154°. In addition, it has good mechanical stability which can be reused and recovered continuously, making it a potential material for practical applications. [ABSTRACT FROM AUTHOR]

Herein, a novel flexible SiO 2 aerogel composite nanofiber membrane with strawberry-like structure and excellent thermal insulation properties, in which SiO 2 aerogel particles act as thermal insulation filler, was prepared by electrospinning technology. With the addition of nano-pore structure SiO 2 aerogel particles, the heat transfer path of the fibers inside the membrane became discontinuous, endowing the as-prepared membrane an ultra-low thermal conductivity of 30.3 mW/(m⋅K) and large surface area of 240 m2/g. Moreover, the nanofibers membrane also possesses the combined merits of excellent fire resistance, high-temperature stability, and temperature-invariant flexibility, rendering it a promising in the application of insulation and gas adsorption. The successful preparation of this flexible nanofiber membrane paves a new way to design materials with excellent thermal insulation and adsorption properties. [ABSTRACT FROM AUTHOR]

Environmental noise has been regarded as major noise pollution with severe hazards to human physical and mental health. The common commercial fiber sound-absorption materials have insufficient low frequencies wave absorbing and fire-resistant ability, limiting their wide application. To solve these problems, a novel strategy combining flexible nanofibers and rGO/MXene nanosheets was proposed to fabricate rGO/MXene/SiO 2 nanofibers composite aerogel with hierarchically porous structure, which possessed an extremely low density of 9.8 mg/cm3 and superior low-frequency sound absorption ability (NRC value of 0.51). The obtained composite aerogel possessed a large deformation up to 80% (corresponding compressive stress of 17 kPa) and quickly recovered. In addition, the as-prepared aerogel could be easily produced on a large scale, providing a reference for the development of new generation of sound-absorbing products. [ABSTRACT FROM AUTHOR]

• Various direct and indirect mitochondrial dysfunction is associated with ALS. • Protein misfolding and abnormal aggregation induce and exacerbate ALS. • An epigenetic perspective on the pathogenesis of ALS is presented. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with multiple complex mechanisms involved. Among them, mitochondrial dysfunction plays an important role in ALS. Multiple studies have shown that mitochondria are closely associated with reactive oxygen species production and oxidative stress and exhibit different functional states in different genetic backgrounds. In this review we explored the roles of Ca2+, autophagy, mitochondrial quality control in the regulation of mitochondrial homeostasis and their relationship with ALS. In addition, we also summarized and analyzed the roles of protein misfolding and abnormal aggregation in the pathogenesis of ALS. Moreover, we also discussed how epigenetic mechanisms such as DNA methylation and protein post-translational modification affect initiation and progression of ALS. Nevertheless, existing events still cannot fully explain the pathogenesis of ALS at present, more studies are required to explore pathological mechanisms of ALS. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate the characteristics and prognosis of 56 patients with rheumatoid arthritis (RA)-associated renal involvement by retrospective review of their renal biopsy specimens. Included in this cross-sectional study were 56 RA patients with renal involvement, in whom renal biopsy was performed to analyze the histological pattern and renal prognosis. IgA nephropathy (IgAN) was detected in 48.2% of the 56 included patients as the most common renal histological pattern, followed by membranous nephropathy (MN) in 23.2% cases, focal segmental glomerular sclerosis (FSGS) in 19.6% cases, chronic interstitial nephritis (CIN) in 5.4% cases, membranoproliferative glomerulonephritis (MPGN) in 1.8% cases, and non-IgA mesangial proliferative glomerulonephritis in 1.8% cases. No significant relationship was observed between the histopathologic type and the RA duration, joint deformity or treatment. Renal dysfunction was mainly found in IgAN patients, and MN occurred more frequently in older patients. Renal function decline occurred in two IgAN patients, one with FSGS and the other with MPGN. Another CIN patient progressed to dialysis during the follow-up period. The patients with renal function decline had a significantly higher level of serum creatinine at presentation. The high percentage of glomeruli sclerosis and interstitial fibrosis/tubular atrophy was also related to renal function decline. IgAN was the major RA-associated renal histological lesion in our series. Renal biopsy can provide useful information about the histological pattern and renal prognosis and therefore should be considered in RA patients with renal involvement. [ABSTRACT FROM AUTHOR]

Abstract: Abundant phenolic compounds, including rosmarinic acid (RA), caffeic acid, and their derivatives, are present in cold‐pressed Perilla frutescens seed flour (CP‐PFSF) after oil extraction. In this study, the in vitro antioxidant and hepatoprotective activities of the major phenolic components of CP‐PFSF were assessed and compared. RA showed the highest antioxidant and hepatoprotective activities. An RA‐rich extract was prepared and its hepatoprotective effects were assessed in vitro and in vivo. In vitro, treatment with RA‐rich extract markedly reduced H2O2‐induced cytotoxicity, significantly prevented H2O2‐induced lipid peroxidation and glutathione depletion, inhibited H2O2‐induced apoptosis by regulating the expression of Bcl‐2/Bax, caspase 9, and caspase 3, which are involved in the mitochondrial apoptosis pathway. In vivo, oral administration of RA‐rich extract significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase, and hepatocyte degeneration and neutrophilic infiltration induced by tert‐butylhydroperoxide (t‐BHP). Therefore, an RA‐rich extract from CP‐PFSF showed potential protective effects against oxidative hepatic damage. Practical applications: Perilla (Perilla frutescens) seed is extensively cold pressed for extraction of cooking oils. However, abundant phenolic compounds still exist in the cold‐pressed Perilla seed flour (CP‐PFSF), which was usually considered useless after oil extraction. In this study, the in vitro antioxidant and hepatoprotective activities of the major phenolic components from CP‐PFSF, including rosmarinic acid (RA), caffeic acid (CA), and their derivatives, were assessed and compared. RA showed the highest antioxidant and hepatoprotective activities. Then, an RA‐rich extract was prepared and its hepatoprotective effects were assessed in vitro and in vivo. The results indicated that RA‐rich extract of CP‐PFSF showed potential hepatoprotective activities, which would broaden our knowledge about the bioactivities of phenolic components in CP‐PFSF, and facilitate the development of CP‐PFSF as candidate functional dietary supplements in food industries. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies reported that exposure to non-traumatic level sounds after traumatic noise exposure reduced the degree of noise-induced hearing loss and hair cell stereocilia damage. The current study investigated the effects of a 3-day post-noise acoustic environment on the degree of noise-induced hearing loss and cochlear damage. Female chinchillas were exposed to traumatic continuous noise (4kHz octave-band noise) at 107dB SPL for 1h and then placed in either an augmented acoustic environment (AAE) or deprived acoustic environment (DAE) for 3days. The AAE group was exposed to a broad-band noise (4–20kHz) at 80dB SPL and the DAE animals were fit with conventional earplugs to minimize the level of acoustic stimulation. Auditory brainstem responses (ABRs) were recorded before and 3days after the traumatic noise exposure. The AAE group showed a significantly lower average threshold shift at the frequencies of 4 and 8kHz (p <0.01). Correspondingly, significantly fewer missing and dying outer hair cells (OHCs) were observed in the AAE group than in the DAE group. Although the cochlear reduced and oxidized glutathione levels (GSH and GSSG, respectively) were essentially the same in two groups at day 3, significant correlations were found between GSSG levels and mean ABR threshold shift (1–16kHz) in the AAE group; as well as GSSG and percentage of total OHC loss in the DAE group. The results suggest that post-noise acoustic environment influenced the degree of hearing loss and OHC deterioration after traumatic noise exposure. [Copyright &y& Elsevier]

Abstract: Apoptotic cell death has been implicated in cochlear degeneration during aging. To better understand the impact and the biological process of outer hair cell (OHC) apoptosis, we investigated the contribution of apoptotic cell death to the formation of the OHC lesions, and observed the temporal patterns of the occurrence of apoptotic events associated with the mitochondrial pathway in Fischer 344/NHsd rats, with ages ranging from 20 to 27 months. The results showed that the ratio of apoptotic to necrotic OHCs was 8:1. During the process of cell degeneration, the onset of Bax expression, cytochrome c release, and nuclear DNA fragmentation preceded the onset of nuclear condensation. In contrast, the activation of caspases-3 and -9, as well as the degradation of F-actin, took place after the onset of nuclear condensation. The results of this study suggest that the initiation of nuclear degradation is a caspase-3-independent process. Moreover, the study revealed that OHCs with Bax expression or cytochrome c release could enter either the apoptotic or necrotic pathway, suggesting the presence of a regulatory mechanism that guides degenerating OHCs to die via either the apoptotic or necrotic pathway. [Copyright &y& Elsevier]

Abstract: Studies of the F344 rat have shown a variety of age-related auditory anatomy and physiology changes. The current study was undertaken to clarify the ARHL in the F344 rat, by examining the auditory pathway of the F344/NHsd substrain that is distributed by Harlan Laboratories for research in the United States. The F344/NHsd rat begins to lose its hearing at about 12 months, and by 24 months, there are 50–60dB auditory brainstem response threshold shifts at 20 and 40kHz and 20dB losses at 5–10kHz. Distortion product otoacoustic emissions (DPOAE) amplitudes at 1.8–12kHz stimuli were depressed in the older (18–24 months) rats. Amplitude input–output functions of the compound action potential (CAP) were also depressed across frequency. The endocochlear potential (EP) was 90–100mV in the 3month old rats. All but one of the 24month old rats’ EPs were in the +75–85mV range. Tympanometry revealed no differences in middle ear function between the young and older rats. Collectively, these findings suggest damage to the outer hair cells, but anatomical examination of the outer hair cells revealed a relative lack of cell loss compared to the magnitude of the hearing and DPOAE loss. [Copyright &y& Elsevier]