Diagnostic value of retinol-binding protein 4 in diabetic nephropathy: a systematic review and meta-analysis.

Objective: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN. Methods: We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated. Results: Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71-0.80] and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test. Conclusion: Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.

High Energy Density in All-Organic Polyimide-Based Composite Film by Doping of Polyvinylidene Fluoride-Based Relaxor Ferroelectrics.

Recently, due to the advantages of superior compatibility, fewer interface defects, and a high electric breakdown field, all-organic dielectric composites have attracted significant research interest. In this investigation, we produced all-organic P(VDF-TrFE-CFE) terpolymer/PI (terp/PI) composite films by incorporating a small amount of terpolymer into PI substrates for high energy density capacitor applications. The resulting terp/PI-5 (5% terpolymer) composite films exhibit a permittivity of 3.81 at 1 kHz, which is 18.7% greater than that of pristine PI (3.21). Furthermore, the terp/PI-5 film exhibited the highest energy density (9.67 J/cm3) and a relatively high charge-discharge efficiency (84.7%) among the terp/PI composite films. The energy density of the terp/PI-5 film was increased by 59.8% compared to that of the pristine PI film. The TSDC results and band structure analysis revealed the presence of deeper traps in the terp/PI composites, contributing to the suppression of leakage current and improved charge-discharge efficiency. Furthermore, durability tests confirm the stability of the composite films under extended high-temperature exposure and cycling, establishing their viability for practical applications.

Curcumenol improves renal function in 5/6 nephrectomy-induced chronic renal failure rats via the SIRT1/NF-κB pathway.

The present work aimed to explore the protective effects of curcumenol and evaluate its pharmacological mechanisms in 5/6 nephrectomy-induced chronic renal failure (CRF). Rats with CRF were administrated curcumenol and the effects on renal functions were investigated. Renal function examinations were carried out, whereas serum levels of inflammatory mediators, including NF-κB, MCP-1 and IL-1ß were analyzed by ELISA. The mRNA expression levels of SIRT1, p65 and IκBα were measured by qRT-PCR, and the SIRT1 protein levels were analyzed by western blot and immunohistochemistry. Our results indicated that curcumenol significantly improved the renal functions in the CRF rats. Compared to the sham group, serum levels of NF-κB, MCP-1, IL-1ß, and the mRNA expression levels of p65 were significantly increased (p < 0.01), whereas the mRNA expression level of IκBα was significantly decreased (p < 0.01) and the SIRT1 levels were dramatically down-regulated (p < 0.05) in the CRF groups. Treatment with curcumenol remarkably inhibited inflammatory responses as reflected by the reduced levels of inflammatory mediators (p < 0.01) and SIRT1 up-regulation (p < 0.05). Our findings suggested that curcumenol could improve the renal function in 5/6 nephrectomy-induced CRF rats, and the mechanisms might involve suppressing the associated inflammation and modulating the SIRT1 and NF-κB signaling pathways.

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins.

The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the Omicron BA.2 spike trimer exhibits 11-fold and 2-fold higher potency in binding to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to efficiently inhibit Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants via a human-cat-mouse-human circle, which could have important implications in establishing an effective strategy for combating SARS-CoV-2 viral infections.

Flexoelectricity-Enhanced Photovoltaic Effect in Self-Polarized Flexible PZT Nanowire Array Devices.

In this investigation, we report the flexoelectricity-enhanced photovoltaic (FPV) effect in a flexible Pb(Zr0.52Ti0.48)O3 nanowire (PZT NW) array/PDMS (polydimethylsiloxane) nanocomposite. The simulation result of density functional theory (DFT) indicated that the FPV effect in PZT NWs can be greatly affected by the interactions of the strain gradients with the internal field generated by self-polarization. We found that when the nanocomposite film was curved down, the photovoltaic current of the aligned PZT-NW/PDMS composite increased by 84.6-fold and 27.6-fold compared with the PZT-nanoparticles/PDMS and randomly aligned PZT-NW/PDMS nanocomposites at the same curvature, respectively. This is mainly ascribed to the increased flexoelectricity in the aligned PZT-NW/PDMS nanocomposite. This study will contribute to a full understanding of the influence of nanoparticle shape on the flexophotovoltaic effect of nanocomposites. It will have potential use in nanocomposites for the study of the FPV effect and associated applications.

Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.

Selection and validation of reference genes for RT-qPCR in adipose and longissimus dorsi muscle tissues of buffalo.

Real-time quantitative PCR (RT-qPCR) is widely used to measure and evaluate gene expression. The precision and reliability of RT-qPCR are critically dependent on the selection of suitable reference genes (RGs). In this study, an effort was made to identify the optimal RGs for RT-qPCR analysis of adipose and the longissimus dorsi muscle (LM) in buffaloes. RNA sequencing data were firstly analyzed to obtain 10 candidate genes (FKBP1A, C25H16orf72, PNRC2, IQGAP1, ATP5PD, RPL6, NDUFB4, TRA2A, CAPRIN1, and METAP2) that with high and stable expression across adipose tissues. Four other identified RGs (GAPDH, ACTB, TOP2B, and UXT) were selected as well. The expression stability of the candidate RGs was evaluated by three algorithms (geNorm, NormFinder, and BestKeeper) and then further validated by adipocyte and myocyte markers. Our results showed that UXT and TOP2B were the optimal RGs for RT-qPCR analysis across adipose tissues in buffaloes; three RGs, RPL6, UXT, and TOP2B, were the optimal RGs for RT-qPCR analysis across adipose and the LM tissues in buffaloes. This study provides significant information for improving the accuracy of gene expression in research on intramuscular fat deposition in buffaloes.

A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

An Omalizumab Biobetter Antibody With Improved Stability and Efficacy for the Treatment of Allergic Diseases.

The critical role of IgE in allergic diseases is well-documented and clinically proven. Omalizumab, a humanized anti-IgE antibody, was the first approved antibody for the treatment of allergic diseases. Nevertheless, omalizumab still has some limitations, such as product instability and dosage restriction in clinical application. In this study, we attempted to develop an omalizumab biobetter antibody with the potential to overcome its limitations. We removed two aspartic acid isomerization hotspots in CDRs of omalizumab to improve antibody candidate's stability. Meanwhile, several murine amino acids in the framework region of omalizumab were replaced with human source to reduce the potential immunogenicity. Yeast display technology was then applied to screen antibody candidates with high binding affinity to IgE. Moreover, YTE mutation in Fc fragment was introduced into the candidates for extending their serum half-life. A lead candidate, AB1904Am15, was screened out, which showed desired biophysical properties and improved stability, high binding affinity and elevated potency in vitro, prolonged half-life in human FcRn transgenic mouse, and enhanced in vivo efficacy in cynomolgus monkey asthma model. Overall, our study developed a biobetter antibody of omalizumab, AB1904Am15, which has the potential to show improved clinical benefit in the treatment of allergic diseases.

Comparative transcriptome analysis reveals that PCK1 is a potential gene affecting IMF deposition in buffalo.

BACKGROUND: In China, although buffaloes are abundant, beef is mainly obtained from cattle, and this preference is mainly attributed to the low intramuscular fat (IMF) content of buffalo. Genetic factors are an important driver that affects IMF deposition. RESULTS: To reveal the intrinsic factors responsible for the low IMF content of buffalo, mRNA expression patterns in muscle and adipose tissue between buffalo and cattle were characterized by RNA sequencing analysis. The IMF content in Nanyang cattle was higher than that in Xinyang buffalo. A total of 1566 mRNAs expressed in adipose tissue showed differential expression between the longissimus dorsi muscles of buffalo and cattle. Functional annotation suggested a difference in the glycolysis/gluconeogenesis pathway between the two species. The results of RT-qPCR analysis and gain-of-function experiments confirmed the positive association between the IMF content and phosphoenolpyruvate carboxykinase 1 (PCK1) expression in buffalo. In both mouse C2C12 cells and cultured bovine myocytes, the activity of the PCK1 promoter in buffalo is lower than that in cattle. However, in mouse 3T3-L1 adipocytes and cultured bovine adipocytes, the activity of PCK1 in buffalo promoter is higher than that in cattle. CONCLUSIONS: These results indicate the important role of PCK1 in buffalo IMF deposition and illustrate the differences between buffalo and cattle promoter activity that drive PCK1 expression. This research helps to establish a foundation for further studies investigating IMF deposition in buffalo.

Impact of human papillomavirus infection in semen on sperm progressive motility in infertile men: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) has been considered as one of the most common sexually transmitted viruses that may be linked to unexplained infertility in men. The possible mechanisms underlying correlation between HPV infection and infertility could be related to the altered sperm parameters. Current studies have investigated the effect of HPV seminal infection on sperm quality in infertile men, but have shown inconsistent results. METHODS: We systematically searched PubMed, Embase, Web of Science and CNKI for studies that examined the association between HPV seminal infection and sperm progressive motility. Data were pooled using a random-effects model. Outcomes were the sperm progressive motility rate. Results are expressed as standardised mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was evaluated by the I-square (I2) statistic. RESULTS: Ten studies were identified, including 616 infertile patients with HPV seminal infection and 2029 infertile controls without HPV seminal infection. Our meta-analysis results indicated that sperm progressive motility was significantly reduced in HPV-infected semen samples compared with non-infected groups [SMD:-0.88, 95% CI:-1.17 ~ - 0.59]. There existed statistical heterogeneity (I2 value: 86%) and the subgroup analysis suggested that study region might be the causes of heterogeneity. CONCLUSIONS: HPV semen infection could significantly reduce sperm progressive motility in infertile individuals. There were some limitations in the study such as the differences in age, sample sizes and the number of HPV genotypes detected. Further evidences are needed to better elucidate the relationship between HPV seminal infection and sperm quality.

Mean effective volume of local anesthetics by nerve conduction technique.

BACKGROUND: This study aimed to investigate whether nerve conduction could be used to objectively evaluate mean effective volume of 1.5% lidocaine after subparaneural or extraparaneural injection. METHODS: Twenty patients undergoing unilateral foot or ankle surgery were randomized into either subparaneural or extraparaneural injection group, and ultrasound-guided continuous popliteal sciatic nerve block was performed. The action potential amplitude of the distal gastrocnemius muscle was monitored. The time of anesthesia onset and dosage of lidocaine were recorded when amplitude declined to 0.5 mV. The operative analgesic effect, score of numeric rating scales, patient's satisfaction, and movement or sensation were recorded during or after surgery. RESULTS: Preoperative dose of local anesthetics (10.7±1.6 vs. 16.2±1.2 mL) and the time of onset (19.4±3.3 vs. 30.4±2.5 min) reduced significantly in the subparaneural group (P<0.05). The intra-operative analgesic effect (1.2±0.422 vs. 1.3±0.483) and the score of resting numeric rating scales (0.6±1.0 vs. 1.9±2.1 and 0.4±0.7 vs. 1.2±1.1) 24 and 48 h after surgery were comparable between groups, but the subparaneural group had markedly lower scores of activity numeric rating scales (0.3±0.6 vs. 2.1±2.0, 0.7±1.2 vs. 2.2±1.9 and 0.5±0.8 vs. 1.5±1.2) at 6, 24 and 48 h, and significantly higher satisfaction (9.7±0.5 vs. 8.8±0.8) (P<0.05). There were no obvious symptoms of movement or sensation within 3 days in two groups. CONCLUSIONS: The nerve conduction can be used to objectively evaluate the mean effective volume of 1.5% lidocaine in different injection groups, and subparaneural injection has more advantages as compared to extraparaneural injection for continuous popliteal sciatic nerve block.

Factors Associated With Minimum Effective Volume of Lidocaine 1.5% for Sciatic Nerve Blocks.

OBJECTIVES: The objectives of this study were to investigate the correlations between the minimum effective volume (MEV) of lidocaine 1.5% for an ultrasound-guided popliteal sciatic nerve block and individual factors including the cross-sectional nerve area, sex, age, body mass index, and the depth of the sciatic nerve and to evaluate the safety of combined femoral and sciatic nerve blocks by monitoring the plasma concentration of local anesthetics. METHODS: Forty patients received combined single-shot femoral and continuous sciatic nerve blocks. The femoral nerve block was performed with an in-plane technique and 15 mL of lidocaine 1.5%. A continuous peripheral nerve block annular tube was positioned between the tibial and peroneal nerves inside the paraneural sheath. Thirty minutes after the femoral nerve block, a loading dose of 5 mL of lidocaine 1.5% was given to block the sciatic nerve after obtaining the maximum compound muscle action potential (CMAP) amplitude using nerve conduction studies. Additional lidocaine 1.5% was pumped at a rate of 30 mL/h through the indwelling annular tube if, after 8 minutes, the CMAP amplitude was still present. The CMAP amplitude monitored by the nerve conduction studies and pinprick tests were recorded every 2 minutes after the administration of lidocaine 1.5%. When the CMAP amplitude decreased to nearly 0 mV, this MEV was recorded. The influences of the cross-sectional area of the sciatic nerve, sex, age, body mass index, and the depth of the sciatic nerve on the MEV were analyzed using stepwise multiple linear regression. Blood samples were collected from 10 patients to evaluate the safety of combined femoral and sciatic nerve blocks by ultra-performance liquid chromatography-tandem mass spectrometry. Blood was drawn at 0 minutes before femoral nerve injection; 0 minutes before sciatic nerve injection; 8 minutes after sciatic nerve injection; and 0, 10, 20, 30, 45, 60, 75, 90, and 120 minutes after the pumping of lidocaine 1.5% stopped. RESULTS: A significant correlation was found between the MEV of lidocaine 1.5% and the cross-sectional area of the sciatic nerve (r=0.459), with a regression equation of the MEV (mL)=5.969+0.095×(the cross-sectional area of the sciatic nerve). The coefficient of determination was 0.211 (P<0.05). The MEV of lidocaine 1.5% for complete sciatic nerve blocks ranged from 7 to 15 mL. The maximum concentrations of lidocaine, monoethylglycinexylidide, and glycinexylidide were 1672.9 (227.6), 265.7 (32.7), and 42.2 (22.4) ng/mL, respectively. CONCLUSIONS: There is a positive correlation between the cross-sectional area of the sciatic nerve and the MEV. The regression equation can help to predict the MEV of lidocaine 1.5% for popliteal sciatic nerve blocks. The maximum concentrations of lidocaine and its metabolites did not approach toxic threshold limits in this study.

Switchable organoplatinum metallacycles with high quantum yields and tunable fluorescence wavelengths.

The preparation of fluorescent discrete supramolecular coordination complexes (SCCs) has attracted considerable attention within the fields of supramolecular chemistry, materials science, and biological sciences. However, many challenges remain. For instance, fluorescence quenching often occurs due to the heavy-atom effect arising from the Pt(II)-based building block in Pt-based SCCs. Moreover, relatively few methods exist for tuning of the emission wavelength of discrete SCCs. Thus, it is still challenging to construct discrete SCCs with high fluorescence quantum yields and tunable fluorescence wavelengths. Here we report nine organoplatinum fluorescent metallacycles that exhibit high fluorescence quantum yields and tunable fluorescence wavelengths through simple regulation of their photoinduced electron transfer (PET) and intramolecular charge transfer (ICT) properties. Moreover, 3D fluorescent films and fluorescent inks for inkjet printing were fabricated using these metallacycles. This work provides a strategy to solve the fluorescence quenching problem arising from the heavy-atom effect of Pt(II), and offers an alternative approach to tune the emission wavelengths of discrete SCCs in the same solvent.

Wenshen Jianpi recipe, a blended traditional Chinese medicine, ameliorates proteinuria and renal injury in a rat model of diabetic nephropathy.

BACKGROUND: Wenshen Jianpi recipe (WSJPR), a blended traditional Chinese medicine, is considered to have the possible beneficial effect on the progression of diabetic nephropathy (DN). This present study was designed to elucidate this protective activity in a rat model with streptozotocin (STZ)-induced DN and to explore the possible underlying mechanism. METHODS: Adult Sprague Dawley (SD) rats were induced to develop DN through intraperitoneal injection of STZ (60 mg/kg). Animals were orally administered saline, WSJPR at 7.5, 15, 30 g/kg, and valsartan (25 mg/kg) daily for 8 weeks. Blood and 24-h urine samples of each rat were collected for biochemical examination at 2-week intervals. Microcirculatory blood flow in the renal cortex and hemorheology index were also measured. At the end of 8 weeks, all rats were sacrificed to obtain the kidney tissues for histological examination and reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the transcriptional levels of nephrin and podocin genes. RESULTS: WSJPR could improve serum total protein (TP) and albumin (ALB), reduce the excretion rates of urine-TP (U-TP), urine-ALB (U-ALB) and urine urea nitrogen (UUN) (P < 0.05), although it did not significantly alter the hyperglycemia. In addition, treatment with WSJPR could strongly reduce blood flow, erythrocyte aggregation index, and ameliorate microcirculation. In histological measurement, WSJPR-treated rats showed a significant amelioration in glomerular hypertrophy and mesangial expansion. By RT-PCR, we found WSJPR up-regulated the nephrin and podocin expression at mRNA levels. CONCLUSION: This study suggested that WSJPR could effectively relieve renal damage and improve renal function of DN rats by ameliorating metabolism disorder and increasing the gene expression of nephrin and podocin, which might be a useful approach for the treatment of DN.

Ultrafast internal conversion dynamics of bilirubin bound to UnaG and its N57A mutant.

Fluorescent proteins (FPs) have become fundamental tools for live cell imaging. Most FPs currently used are members of the green fluorescent protein super-family, but new fluorophores such as bilin-FPs are being developed and optimized. In particular, the UnaG FP incorporates bilirubin (BR) as a chromophore, enhancing its fluorescence quantum yield by three orders of magnitude relative to that in solution. To investigate the mechanism of this dramatic enhancement and provide a basis for further engineering of UnaG and other tetrapyrrole-based fluorophores, we performed picosecond fluorescence and femtosecond transient absorption measurements of BR bound to UnaG and its N57A site-directed mutant. The dynamics of wt-UnaG, which has a fluorescence QY of 0.51, are largely homogeneous, showing an excited state relaxation of ∼200 ps, and a 2.2 ns excited-state lifetime decay with a kinetic isotope effect (KIE) of 1.1 for D2O vs. H2O buffer. In contrast, for UnaG N57A (fluorescence QY 0.01) the results show a large spectral inhomogeneity with excited state decay timescales of 47 and 200 ps and a KIE of 1.4. The non-radiative deactivation of the excited state is limited by proton transfer. The loss of direct hydrogen bonds to the endo-vinyl dipyrrinone moiety of BR leads to high flexibility and structural heterogeneity of UnaG N57A, as seen in the X-ray crystal structure.

Kilohertz high-frequency alternating current blocks nerve conduction without causing nerve damage in rats.

BACKGROUND: In recent years, 2-50 kHz high-frequency alternating current has been shown to block nerve conduction mostly based on simulation models or experiments in vitro. This study aimed to assess the nerve block effects and related parameters of kilohertz alternating current in a rat model. METHODS: High-frequency biphasic rectangular stimulus pulse was applied to rat's sciatic nerve in vivo, and its blockade frequency and intensity was studied by recording the changes of compound muscle action potential (CMAP) amplitude and muscle states before and after stimulation. Secondly, diameter and circumference of sciatic nerve was measured at stimulating point by ultrasound. The correlation between stimulus' frequency and the nerve's diameter and circumference was studied. Lastly, we assessed nerve damage causing by high-frequency electrical stimulation by measuring CMAP and nerve conduction velocity (NCV) in the following day and sciatic nerve hematoxylin-eosin staining, both blocked side and contralateral side. RESULTS: When the current intensity was fixed, the blockade only occurred in a specific frequency range, above or below might have partial block effect. Preliminary statistical results showed that the blocking frequency of high-frequency alternating current was negatively linearly correlated with the circumference of sciatic nerve (P<0.05); HE staining of the sciatic nerve showed no axon and myelin sheath damage on blocked or opposite side, and the CMAP and NCV of the sciatic nerve remeasured in the next day were normal, indicating high-frequency electrical stimulation produced no nerve injury. CONCLUSIONS: High-frequency alternating current stimulation can block nerve conduction without causing nerve damage, and the complete block frequency is negatively linearly correlated with the circumference of sciatic nerve.

The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis.

Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVß3 and α5ß1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the inflammatory response. However, due to its short half-life, the anti-RA activity was achieved by frequent administration. To extend the half-life of HM-3, we designed a fusion protein with name HM-3-Fc, by combination of modified Fc segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic lymphocytes and reduced the release of TNF-α from macrophages. The pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg groups, or once in 7 days in the 25 mg/kg group showed a better protective effect within two weeks than the positive control adalimumab and HM-3 group. Preliminary pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM-3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated that an Fc fusion can effectively increase the half-life of HM-3 and make it possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a long-acting active molecule for RA treatment.

A perspective for improving the sensitivity of detection: The application of multi-epitope recombinant antigen in serological analysis of buffalo schistosomiasis.

The sensitivity and specificity are two crucial aspects of addressing the efficacy of diagnostic antigens. Achilles' heel of low sensitivity rate exists in current diagnostic recombinant antigens for schistosomiasis detection. This study focused on the diagnosis of water buffalo schistosomiasis japonica and a perspective of improving recombinant antigens' sensitivity was assessed using archived 220 water buffalo sera (114 positive sera, 92 negative sera and 14 Paramphistomum-infected sera) and the method of enzyme-linked immunosorbent assay (ELISA). The subjects included two trivalent recombinant proteins, one bivalent antigen and two single-molecular antigens. The crude antigen SEA (soluble egg antigen) was employed as reference antigen. The highest sensitivity rate in the five recombinant antigens assigned to the trivalent multi-epitope antigen PA4 (95.61%, 109/114), no significant difference with SEA (100%, 114/114, p = .836), and showing remarkable differences with the two single-molecular antigens (p < 0.01). In term of specificity, two trivalent multi-epitope antigens PA4 (97.83%, 90/92), PA5 (100%, 92/92) and the bivalent antigen PA3 (98.91%, 91/92) had few differences with one monovalent antigens PA1 (97.83%, 90/92, p = .304/0.103/0.640), significant differences with another monovalent antigens PA2 (92.39%, 85/92, p < 0.01) and SEA (82.61%, 76/92, p < 0.01). Additional, all the recombinant antigens had low cross-reactivity (7.14%, 1/14, 0% for PA5) with serum samples of paramphistomiasis, contrast with that of SEA (50%, 7/14, p < 0.01). The results indicated that multi-epitope antigens have the possibility to improve diagnostic sensitivity and the trivalent multi-epitope antigen PA4 possesses greater likelihood to be a diagnostic antigen for water buffalo schistosomiasis.

Proteomic profile of human spermatozoa in healthy and asthenozoospermic individuals.

Asthenozoospermia is considered as a common cause of male infertility and characterized by reduced sperm motility. However, the molecular mechanism that impairs sperm motility remains unknown in most cases. In the present review, we briefly reviewed the proteome of spermatozoa and seminal plasma in asthenozoospermia and considered post-translational modifications in spermatozoa of asthenozoospermia. The reduction of sperm motility in asthenozoospermic patients had been attributed to factors, for instance, energy metabolism dysfunction or structural defects in the sperm-tail protein components and the differential proteins potentially involved in sperm motility such as COX6B, ODF, TUBB2B were described. Comparative proteomic analysis open a window to discover the potential pathogenic mechanisms of asthenozoospermia and the biomarkers with clinical significance.