Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

Miniature tunable Airy beam optical meta-device

Tunable Airy beams with controllable propagation trajectories have sparked interest in various fields,such as optical manipulation and laser fabrication.Existing research approaches encounter challenges related to insufficient compactness and integration feasibility,or they require enhanced tunability to enable real-time dynamic manipulation of the propagation trajectory.In this work,we present a novel method that utilizes a dual metasurface system to surpass these limitations,significantly enhancing the practical potential of the Airy beam.Our approach involves encoding a cubic phase profile and two off-axis Fresnel lens phase profiles across the two metasurfaces.The validity of the proposed strategy has been confirmed through simulation and experimental results.The proposed meta-device addresses the existing limitations and lays the foundation for broadening the applicability of Airy beams across diverse domains,encompassing light-sheet microscopy,laser fabrication,optical tweezers,etc.

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs

Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group(n=3)and a non-susceptible group(n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.

Light-based 3D printing of stimulus-responsive hydrogels forminiature devices:recent progress and perspective

Miniature devices comprising stimulus-responsive hydrogels with high environmental adaptability are now considered competitive candidates in the fields of biomedicine,precise sensors,and tunable optics.Reliable and advanced fabricationmethods are critical formaximizing the application capabilities ofminiature devices.Light-based three-dimensional(3D)printing technology offers the advantages of a wide range of applicable materials,high processing accuracy,and strong 3D fabrication capability,which is suitable for the development of miniature devices with various functions.This paper summarizes and highlights the recent advances in light-based 3D-printed miniaturized devices,with a focus on the latest breakthroughs in lightbased fabrication technologies,smart stimulus-responsive hydrogels,and tunable miniature devices for the fields of miniature cargo manipulation,targeted drug and cell delivery,active scaffolds,environmental sensing,and optical imaging.Finally,the challenges in the transition of tunable miniaturized devices from the laboratory to practical engineering applications are presented.Future opportunities that will promote the development of tunable microdevices are elaborated,contributing to their improved understanding of these miniature devices and further realizing their practical applications in various fields.

Miniaturized power detection module operating in millimeter wave band

The miniaturized broadband detection module can be embedded into the microwave application system such as the front end of the transmitter to detect the power or other parameters in real time.It is highly prospective in military and scientific research.In this paper,a broadband power detection module operating at 26.5 GHz-40.0 GHz is designed by using low-barrier Schottky diode as the detector and a comparator for threshold output.This module can dynamically detect the power range between-10 dBm and 10 dBm with the detection accuracy of 0.1 dB.Further,the temperature compensation circuit is also applied to improve the measurement error.As a result,the resulted error low to±1 dB in the temperature range of -55℃ to +85℃ is achieved.The designed module is encapsulated by a Kovar alloy with a small volume of 9 mm×6 mm×3 mm.This endows the designed module the advantages of small size,easy integration,and low cost,and even it is applicable to high-reliability environments such as satellites.

Investigating the expression profiles of cysteine string proteins(CSPs)in cochlear tissue

Objective:This study aims to explore the expression patterns of cysteine string protein alpha(CSPα)and cysteine string protein beta(CSPβ)in the mammalian inner ear,with an emphasis on their temporal dynamics during the developmental stages of C57BL/6 mice.Methods:We utilized immunofluorescence staining to assess the localization and distribution of CSPαand CSPβwithin the inner ears of C57BL/6 mice and miniature pigs.Additionally,this method facilitated the investigation of their temporal expression profiles.Results:In adult C57BL/6 mice and miniature pigs,CSPαand CSPβwere identified in the cytoplasm of inner hair cells and spiral ganglion cells,yet were absent in outer hair cells.Both proteins were found to colocalize with Ctbp2 on the basal side of the cytoplasm in inner hair cells’basilar membrane.Expression of CSPαwas observed at the nerve fiber termini at the basilar membrane’s base of inner and outer hair cells 10 days postnatally in C57BL/6 mice.Notably,expression of both CSPαand CSPβin the cytoplasm of inner hair cells emerged on the 12th day post-birth,aligning with the timeline for registering cochlear potentials.The expression levels of both proteins increased with age,but were consistently absent in outer hair cells.Contrastingly,expression of CSPαand CSPβwas present in the cytoplasm of inner hair cells in miniature pigs as early as one day post-birth,yet remained absent in the three rows of outer hair cells.Conclusion:CSPαand CSPβexhibit predominant and specific expression in inner hair cells and spiral ganglion cells.A unique expression pattern was observed for CSPα,which was also present at the nerve fiber endings of both inner and outer hair cells.The developmental expression trajectory of CSPαand CSPβin mouse inner hair cells is characterized by an initial absence,followed by a gradual increase.Moreover,the timing of expression onset between mice and miniature pigs indicates distinct temporal dynamics,suggesting a potential role in auditory development.

Identifying the enhancement mechanism of Al/MoO_(3) reactive multilayered films on the ignition ability of semiconductor bridge using a one-dimensional gas-solid two-phase flow model

Energetic Semiconductor bridge(ESCB)based on reactive multilayered films(RMFs)has a promising application in the miniature and intelligence of initiator and pyrotechnics device.Understanding the ignition enhancement mechanism of RMFs on semiconductor bridge(SCB)during the ignition process is crucial for the engineering and practical application of advanced initiator and pyrotechnics devices.In this study,a one-dimensional(1D)gas-solid two-phase flow ignition model was established to study the ignition process of ESCB to charge particles based on the reactivity of Al/MoO_(3) RMFs.In order to fully consider the coupled exothermic between the RMFs and the SCB plasma during the ignition process,the heat release of chemical reaction in RMFs was used as an internal heat source in this model.It is found that the exothermal reaction in RMFs improved the ignition performance of SCB.In the process of plasma rapid condensation with heat release,the product of RMFs enhanced the heat transfer process between the gas phase and the solid charge particle,which accelerated the expansion of hot plasma,and heated the solid charge particle as well as gas phase region with low temperature.In addition,it made up for pressure loss in the gas phase.During the plasma dissipation process,the exothermal chemical reaction in RMFs acted as the main heating source to heat the charge particle,making the surface temperature of the charge particle,gas pressure,and gas temperature rise continuously.This result may yield significant advantages in providing a universal ignition model for miniaturized ignition devices.

Current Situation and Progress of Pig Model in Otology Research

Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. This article introduces the applications, current status, progress, advantages, and issues of using pigs as otologic animal models. It summarizes current research on pigs in the fields of hearing disorders, otitis, vertigo, cochlea, gene editing, and tissue engineering, among other otologic and audiological areas. These models are valuable for translating basic medical science into clinical applications. Based on this, platforms have been established for studying deafness and vertigo, cochlear implantation experiments, stem cell and gene therapy, and tissue engineering. These serve as ideal experimental models for the prevention and treatment of ear diseases, pointing toward new directions. This will bolster the promotion and application of pig models in the fields of tissue engineering and gene editing in the future.

Cloning and Sequence Analysis on cDNA of Growth Hormone Releasing Hormone Receptor Gene from Wuzhishan Miniature Pig

[Objective] cDNA of growth hormone releasing hormone （GHRH） receptor gene from Wuzhishan miniature pig was cloned and its sequence was also analyzed. [Method] Using genomic DNA extracted from porcine ear tissues of Wuzhishan miniature pig as the template, three pairs of primers were designed by the reported cDNA sequence of porcine GHRH, and cDNA was also amplified by RT-PCR. After being recovered and purified, PCR products were ligated to pMD18-T and then transformed into Escherichia coli DH5a. The transformation products were analyzed by PCR and double enzyme digestion to screen positive clones, and the positive clones were sequenced after identification in LB liquid medium. [ Result] cDNA of Wuzhishan miniature pig GHRH receptor gene was obtained successfully, and its length was 1 577 bp coding 423 amino acids. BLAST analysis showed that there were only 23 nuoleotides in difference between this fragment and pomine GHRH receptor gene, and its homology was 98%. However, both GHRH receptor genes were constituted by 423 amino acids with the sequence homology of 96%. [ Conclusion] This study provides theoretical basis for further studies on the dwarf mechanism of Wuzhishan miniature pig.

TECA hybrid artificial liver support system in treatment of acute liver failure

AIM: To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF). METHODS: The porcine liver cells (1-2) x 10(10) were separated from the Chinese small swine and cultured in the bioreactor of TECA-BALSS at 37.0 degrees C and circulated through the outer space of the hollow fiber tubes in BALSS. The six liver failure patients with various degree of hepatic coma were treated by TECA-HALSS and with conventional medicines. The venous plasma of the patients was separated by a plasma separator and treated by charcoal adsorbent or plasma exchange. The plasma circulated through the inner space of the hollow fiber tubes of BALSS and mixed with the patients' blood cells and flew back to their blood circulation. Some small molecular weight substances were exchanged between the plasma and porcine liver cells. Each treatment lasted 6.0-7.0 h. Physiological and biochemical parameters were measured before,during and after the treatment. RESULTS: The average of porcine liver cells was (1.0-3.0) x 10(10) obtained from each swine liver using our modified enzymatic digestion method. The survival rate of the cells was 85%-93% by trypan blue stain and AO/PI fluorescent stain. After cultured in TECA-BALSS bioreactor for 6 h, the survival rate of cells still remained 70%-85%. At the end of TECA-HALSS treatment, the levels of plasma NH(3), ALT, TB and DB were significantly decreased. The patients who were in the state of drowsiness or coma before the treatment improved their appetite significantly and regained consciousness, some patients resumed light physical work on a short period after the treatment.One to two days after the treatment, the ratio of PTA increased warkedly. During the treatment, the heart rates, blood pressure, respiration condition and serum electrolytes (K(+), Na(+) and Cl(-)) were stable without thrombosis and bleeding in all the six patients. CONCLUSION: TECA-HALSS treatment could be a rapid, safe and efficacious method to provide temporary liver support for patients with ALF.

Cloning and cDNA Sequence Analysis of SLA-DQA Gene from Hainan Wuzhishan Miniature Pig

[ Objective] The study aimed to lay a foundation for studying immune recognition mechanism in xenotransplantation. [ Method] SLA- DQA gene of Hainan Wuzhishan miniature pig was cloned by RT-PCR and sequenced. J-Result] The SLA-DQA gene sequence of Wuzhishan minia- ture pig contained 768 nucleotides, among which 1 -765 were the complete open reading frame, encoding 255 amino acids. SLA-DQA cDNA se- quence and its deduced amino acid sequence of Wuzhishan miniature pig were most similar to those of the other miniature pigs in China. When compared with corresponding cDNA sequences and the amino acid sequences in other species, the homology with human was obviously higher than that with mouse. [ Conclusion] As the Chinese pig breed suitable for xenotransplantation, Wuzhishan miniature pig has significant importance to ser- ial studies on immunogenetics characteristics.

Retrograde intrarenal surgery vs miniaturized percutaneous nephrolithotomy to treat lower pole renal stones 1.5-2.5 cm in diameter

AIM To compare the outcomes of retrograde intrarenal surgery(RIRS) and miniaturized percutaneous nephrolithotomy(mini-PCNL) in treating lower pole(LP) renal stones with a diameter of 1.5-2.5 cm.METHODS A total of 216 patients who underwent mini-PCNL(n = 103) or RIRS n = 113) for LP stones with a diameter of 1.5-2.5 cm were enrolled between December 2015 and April 2017 at the Urology Department of Ningbo Urology and Nephrology Hospital.RESULTS Significant differences were found in the hospital stay(9.39 ± 4.01 vs 14.08 ± 5.26, P < 0.0001) and hospitalization costs(2624.5 ± 513.36 vs 3255.2 ± 976.5, P < 0.0001) between the RIRS and mini-PCNL groups. The mean operation time was not significantly different between the RIRS group(56.48 ± 24.77) and the mini-PCNL group(60.04 ± 30.38, P = 0.345). The stone-free rates at the first postoperative day(RIRS vs mini-PCNL: 90.2% vs 93.2%, P = 0.822) and the second month postoperatively(RIRS vs mini-PCNL: 93.8% vs 95.1%, P = 0.986) were not significantly different.CONCLUSION RIRS and mini-PCNL are both safe and effective methods for treating LP stones with a diameter of 1.5-2.5 cm. RIRS can be considered as an alternative to PCNL for the treatment for LP stones of 1.5-2.5 cm.

Heat Stress Upregulates the Expression of TLR4 and Its Alternative Splicing Variant in Bama Miniature Pigs

Alternative splicing is a cellular mechanism in eukaryotes that results in considerable diversity ofgene products. It plays an important role in several diseases and cellular signal regulation. Heat stress is a major factor that induces immunosuppression in pigs. Little is known about the correlation between alternative splicing and heat stress in pigs. Therefore, this study aimed to clone, sequence and quantify the alternative splicing variant of toll-like receptor 4 （TLR4） in Bama miniature pigs （Sus scrofa domestica） following exposure to heat stress. The results showed that the second exon of TLR4 was spliced and 167 bp shorter in the alternative splicing variant, and the protein was putatively identified as a type of truncated membrane protein consisting of extramembrane, transmembrane and intramembrane regions lacking a signal peptide. Further, it was not a non- classical secretory protein. Five potential reference genes were screened for their potential as reliable standards to quantify the expression of TLR4 alternative spliced variants by real-time quantitative reverse-transcriptase polymerase chain reaction （qRT-PCR）. The stability of these reference genes was ranked using the geNorm and NormFinder programs, and ribosomal protein L4 （RPL4） and TATA box-binding protein （TBP） were found to be the two genes showing the most stable expression in the in vitro cultured peripheral blood mononuclear ceils （PBMCs） during heat shock. The mRNA level of the TLR4 gene （both classical and spliced） in stressed pigs increased significantly （P〈0.05）. Further, the expression levels of the alternative spliced variant of TLR4 （TLR4-ASV） showed a 2-3 folds increase in heat-stressed PBMCs as compared to control pigs. The results of the present study suggested that heat shock might modulate the host immune response by regulating the expressions of TLR4 and its alternative splicing variant.

Oncogenic activity of MCM7 transforming cluster

The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.

Efficacy of biofeedback therapy via a mini wireless device on sleep bruxism contrasted with occlusal splint:a pilot study

The putative causes of bruxism are multifactorial and there are no definite measures for bruxism management.The aim of this study was to evaluate the efficacy of biofeedback therapy on sleep bruxism,compared with occlusal splint.Twenty-four volunteers with sleep bruxism were divided into two groups：the GTB group that were treated with biofeedback therapy（n 512） and the GTO group that were treated with occlusal splint（n 512）.A mini pressure sensor integrated with a monitoring circuit by use of a maxillary biofeedback splint was fabricated.To foster the relaxation of the masticatory muscles and the nervous system,the wireless device received signals from bruxism events and vibrations alerted the bruxer when the threshold was exceeded.Total episodes and average duration of bruxism events during8 hours of sleep were analyzed with the monitoring program（TRMY1.0）.After 6 and 12 weeks,the episodes（P 50.001） and duration（P,0.05） in the GTB group declined dramatically.In contrast,there were no significant differences in the GTO group after the treatment（P.0.05）.Furthermore,the episodes had significant differences between the GTB group and the GTO group after the same period of treatment（P 5 0.000）.The results suggest that biofeedback therapy may be an effective and convenient measure for mild bruxers,when compared with occlusal splint therapy.The mini wireless biofeedback method may be of value for the diagnosis and management of bruxism in the future.

Ex-PRESS implantation with phacoemulsification in POAG versus CPACG

AIM： To compare the long-term outcomes of the Ex-PRESS miniature glaucoma device implanted under a scleral flap in combination of phacoemulsification with intraocular lens implantation in primary open angle glaucoma （POAG） and chronic primary angle-closure glaucoma （CPACG）.METHODS： Retrospective, comparative study. A total of 60 eyes （60 patients） receiving the Ex-PRESS miniature glaucoma device implantation combined with phacoemulsification were reviewed. Thirty eyes （30 patients） had the combined procedures for POAG, and the other 30 eyes （30 patients） for CPACG. RESULTS： The follow-up was 39.37±7.09mo （range 3 to 49mo） in patients with POAG and 37.10±9.26mo （range 9 to 49mo） in patients with CPACG （P=0.29）. The mean change in best corrected visual acuity was 0.41 logMAR for POAG and 0.38 logMAR for CPACG at the last follow-up （P=0.22）. The postoperative intraocular pressure （IOP） of the POAG group was significantly lower than the CPACG group at 1, 3, 12, and 18mo after surgery （P=0.02, 0.00, 0.04, 0.01） with similar glaucoma medications after surgery （P〉0.16）. At 3y after surgery, the cumulative complete and qualified success rates were 63.3% （POAG） and 53.3% （CPACG）, 83.3% （POAG） and 73.3% （CPACG） （P=0.41, 0.49）, respectively. The POAG group had more hypotony than the CPACG group （P=0.04）.CONCLUSION： The long-term outcomes show the Ex-PRESS implantation combined with phacoemulcification can effectively lower the IOP in both the POAG and CPACG groups. The POAG group seems to have lower postoperative IOP and a higher risk of hypotony.

Porous Flame-retarded Asphalt Pavement for Highway Tunnel

A new way to improve the tunnel fire protection by using flame-retarded porous asphalt pavement containing ATH powders was introduced. Based on the miniature burning test designed and conducted, the burning time and temperature of porous asphalt （PA） and flame-retarded porous asphalt （FRPA） were studied comparing with cement concrete pavement, dense-graded lIMA and SMA. Results of burning test and pavement performance test indicate that FRPA is appropriate and suitable as the pavement material of highway tunnel.

小型猪(Miniature pig)

实验动物,在人们传统的观念里,只有鼠、兔、狗、猫、猴等类。但是近代动物模型的开发和比较医学的发展,使得实验动物的种类不断增加,除了传统的经济动物已在动物实验中被大量使用之外,丰富的野生动物资源也不断地得到了开发。例如:麻疯病,多年找不到动物模型。

Characterization and map-based cloning of miniature2-m1, a gene controlling kernel size in maize

Kernel development plays an important role in determining kernel size in maize.Here we present the cloning and characterization of a maize gene,nitrate transporter1.5(NRT1.5),which controls small kernel phenotype by playing an important role in kernel development.A novel recessive small kernel mutant miniature2-m1(mn2-m1)was isolated from self-pollinated progenies of breeding materials.The mutant spontaneously showed small kernel character arresting both embryo and endosperm development at an early stage after pollination.Utilizing 21 polymorphic SSR markers,the mn2-m1 locus was limited to a 209.9-kb interval using 9176 recessive individuals of a BC1 segregating population from mn2-m1/B73.Only one annotated gene was located in this 209.9 kb region,Zm00001 d019294,which was predicted to encode nitrate transporter1.5(NRT1.5).Allelism tests confirmed that mn2-m1 was allelic to miniature2-m2(mn2-m2)and miniature2-710 B(mn2-710 B).The mn2-m1 and mn2-m2 alleles both had nucleotide deletions in the coding region resulting in premature termination,and the mn2-710 B allele had some missence mutations.Subcellular localization showed that Miniature 2(MN2)is localized in the plasma membrane.Quantitative real-time PCR(qRT-PCR)analysis revealed that the expression of MN2 and some genes involved in the basal endosperm transfer layer(BETL)and embryo surrounding region(ESR)development were affected in mn2-m1 seeds.These results suggested that MN2 plays an important role in maize seed development.

Minimally invasive open dismembered pyeloplasty technique: Miniature incision, muscle-splitting dissection, and nopelvis reduction in children

Objective:To report the outcomes and complications of open dismembered Anderson-Hynes pyeloplasty with miniature incision in treating children’s ureteropelvic junction obstruction.Methods:Between March 2007 and April 2011,109 children with a mean age of 2 years and 8 months old with ureteropelvic junction obstruction underwent open dismembered pyeloplasty.Clinical manifestations,radiographic assessments,incision size,surgery time,hospital stay,and complication rate were recorded.All patients had a documented ureteropelvic junction obstruction(having T1/2 more than 20 min in diethylenetriaminepentaacetic acid[DTPA]scan)with symptomatic stenosis or decreased kidney function(differential function<40%).Pyeloplasty was done by a retroperitoneal flank approach with miniature incision without pelvis reduction.One surgeon did all the surgeries.Success rate and complications were assessed in a 3-year follow-up.Results:Mean surgery time was 52 min(47e60 min).Incision size was 18e28 mm.Mean hospital stay was 3 days(2e8 days).The surgery was successful in 98.2%of patients with a mean follow-up time of 36 months(success was defined as disappearance of symptoms,if present,with improved ultrasound imaging results or Reno graphic parameters).The complication rate was 7.33%,including urinary leakage,double-J urethral stent dislocation and infection.Conclusion:Open dismembered pyeloplasty is a safe,technically feasible and effective therapy in treatment of children’s ureteropelvic junction obstruction.It takes a short time to do,requires a small incision and has few complications and a short recovery period.