Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC. METHODS: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts. RESULTS: Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone. CONCLUSIONS: These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.

Electrodeposition of (111)-oriented and nanotwin-doped nanocrystalline Cu with ultrahigh strength for 3D IC application.

The mechanical performance of electroplated Cu plays a crucial role in next-generation Cu-to-Cu direct bonding for the three-dimension integrated circuit (3D IC). This work reports direct-current electroplated (111)-preferred and nanotwin-doped nanocrystalline Cu, of which strength is at the forefront performance compared with all reported electroplated Cu materials. Tension and compression tests are performed to present the ultrahigh ultimate strength of 977 MPa and 1158 MPa, respectively. The microstructure of nanoscale Cu grains with an average grain size around 61 nm greatly contributes to the ultrahigh strength as described by the grain refinement effect. A gap between the obtained yield strength and the Hall-Petch relationship indicates the presence of extra strengthening mechanisms. X-ray diffraction and transmission electron microscopy analysis identify the highly (111) oriented texture and sporadic twins with optimum thicknesses, which can effectively impede intragranular dislocation movements, thus further advance the strength. Via filling capability and high throughput are also demonstrated in the patterned wafer plating. The combination of ultrahigh tensile/compressive strength, (111) preferred texture, superfilling capability and high throughput satisfies the critical requirement of Cu interconnects plating technology towards the industrial manufacturing in advanced 3D IC packaging application.

Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice.

Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions.

Efficient and Adhesiveless Metallization of Flexible Polyimide by Functional Grafting of Carboxylic Acid Groups.

Surface metallization of polyimide (PI) is the key process for the preparation of flexible printed circuit boards (FPCBs). To meet the miniaturization demand, the ultrathinness of FPCB by the removal of the intermediate adhesive layer is imperative. The common adhesiveless process relies on the surface activation of hydrophobic PI through alkaline hydrolysis to generate the hydrophilic carboxylate anion sites for the metallic deposition. However, the alkaline hydrolysis process involves the imide ring cleavage caused by the attack of a strong nucleophile (OH-), resulting in mechanical destruction and surface coarseness of PI. In this study, a new PI is synthesized with the grafting of carboxylic acid groups as the active sites to intrinsically activate PI for efficient metallization. The surface activation is accomplished through an acid-base neutralization reaction in a dilute alkaline environment, which can suppress the alkaline hydrolysis reaction. The attenuated total reflection Fourier transform infrared spectroscopy analysis confirms a significant reduction of the extent of the imide ring cleavage in the carboxylic acid-grafted PI films. According to the microstructural examination using transmission electron microscopy, the deposited metal film adheres firmly to the carboxylic acid-grafted PI films through an interlocking effect of a broccoli bud-shaped nanocluster layer.

Biomimetic Syntheses of (±)-Isopalhinine†A, (±)-Palhinine†A, and (±)-Palhinine†D.

The first total synthesis of isopalhinine A, as well as unified syntheses of palhinine A and palhinine D, were successfully accomplished by means of a biomimetic strategy that proceeds through a bioinspired 5/6/6/9 tetracyclic intermediate, which mimics the amino ketone form of palhinine D. An early-stage direct SN 2 cyclization to construct the nine-membered azonane ring minimized the transannular strain that would otherwise be increased by the twisted nature of the isotwistane skeleton. Then, a diastereoselective Diels-Alder reaction of a masked ortho-benzoquinone using the nine-membered ring as a steric shielding group furnished a functionalized 6/6/9 tricyclic skeleton and established the desired stereochemistry at the C3, C7, C12, and C15 positions in one step. A thiol-mediated acyl radical cyclization gave the bioinspired intermediate bearing three differentiated oxygen-containing functional groups, from which all three total syntheses could be completed in either two or three additional steps.

A fluorescent pH probe for acidic organelles in living cells.

A water-soluble pH sensor, 2-(6-(4-aminostyryl)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-N, N-dimethylethanamine (ADA), was synthesized based on the molecular design of photoinduced electron transfer (PET) and intramolecular charge transfer (ICT). The fluorescence emission response against a pH value is in the range 3-6, which is suitable for labelling intracellular pH-dependent microenvironments. After biological evolution, ADA is more than a pH biosensor because it is also an endocytosis pathway tracking biosensor that labels endosomes, late endosomes, and lysosome pH gradients. From this, the emissive aggregates of ADA and protonated-ADA in these organs were evaluated to explore how this probe stresses emission colour change to cause these unique cellular images.

Supplementary effects of higher levels of various disaccharides on processing yield, quality properties and sensory attributes of Chinese - style pork jerky.

OBJECTIVE: This study evaluated the supplementary effect of higher concentrations of various disaccharides on processing yield, major physicochemical properties, and sensory attributes of Chinese-style pork jerky (CSPJ). METHODS: CSPJ samples were prepared by marinating sliced ham (4 mm) with three dissaccharides, including sucrose, lactose, and maltose, at 0%, 15%, 18%, 21%, and 24%. Subsequently, the CSPJ samples were dried and roasted. The moisture content, water activity, crude protein, moisture-to-protein ratio, pH, processing yield, shear force, color, and sensory attributes of the CSPJ samples were evaluated. RESULTS: The quality characteristics of CSPJ samples prepared with sucrose were more acceptable. By contrast, CSPJ samples prepared with lactose showed the lowest scores. However, the processing yield and moisture content were the highest for CSPJ samples prepared with lactose, which may be associated with improved benefits for cost reduction. Furthermore, sucrose and lactose supplementation resulted in contrasting quality characteristics; for example, CSPJ samples with sucrose and maltose supplementation had higher sensory scores for color than samples with lactose supplementation. Additionally, most quality characteristics of CSPJ samples with sucrose supplementation contrasted with those of the samples with lactose supplementation; for example, the samples with sucrose supplementation had higher scores for sensory attributes than those with lactose supplementation. CONCLUSION: Sucrose supplementation up to 21% to 24% was associated with the highest overall acceptability scores (5.19 to 5.80), enhanced quality characteristics, increased processing yield, and reduced production cost.

Potentially hypervirulent Clostridium difficile PCR ribotype 078 lineage isolates in pigs and possible implications for humans in Taiwan.

Clostridium difficile is a human and animal pathogen. Recently, the incidence of community-acquired C. difficile infection has increased, and many studies have indicated that C. difficile might be food-borne. The correlation between C. difficile infection in humans and in animals has been a topic of debate. The objective of this study was to determine the genetic relatedness of C. difficile from human and pigs in Taiwan. We investigated the molecular epidemiology of C. difficile in healthy humans and pigs from 2011 to 2015. The isolation rate of C. difficile from pigs in 13 commercial farms was 49% (100/204), and a high proportion of hypervirulent (C. difficile carrying tcdA, tcdB, and cdtA/B genes and a 39-bp deletion in the tcdC gene) ribotype 078 lineage isolates (90%, 90/100; including 078, 126, 127, and 066-like isolates) were identified. In addition, the C. difficile ribotype 127 isolates from pigs typically exhibited moxifloxacin resistance (37/43; 86%). In healthy humans, the isolation rate was 4.3% (3/69), and all healthy human isolates were non-toxigenic. In particular, we compared the porcine isolates with two patient strains (ribotype 127) obtained from two hospitals in central Taiwan. The multilocus variable number tandem repeat analysis revealed a high genetic relatedness between ribotype 127 from patients and pigs. This study indicated that isolates of the ribotype 078 lineage, and especially ribotype 127, were widely distributed in pig farms and showed a high frequency of moxifloxacin resistance. The closely related ribotype 127 from patients and pigs may have had a common origin or low diversity. In conclusion, C. difficile ribotype 127 is a noteworthy pathogen in pigs and poses a potential public health threat.

PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression.

The dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses is crucial for synaptic transmission, plasticity, learning, and memory. The protein interacting with C-kinase 1 (PICK1) directly interacts with GluA2/3 subunits of the AMPARs. Although the role of PICK1 in regulating AMPAR trafficking and multiple forms of synaptic plasticity is known, the exact molecular mechanisms underlying this process remain unclear. Here, we report a unique interaction between PICK1 and all three members of the protein kinase C and casein kinase II substrate in neurons (PACSIN) family and show that they form a complex with AMPARs. Our results reveal that knockdown of the neuronal-specific protein, PACSIN1, leads to a significant reduction in AMPAR internalization following the activation of NMDA receptors in hippocampal neurons. The interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis. Similarly, the binding of PICK1 to the ubiquitously expressed PACSIN2 is also regulated by the homologous phosphorylation sites within the PACSIN2-variable region. Genetic deletion of PACSIN2, which is highly expressed in Purkinje cells, eliminates cerebellar long-term depression. This deficit can be fully rescued by overexpressing wild-type PACSIN2, but not by a PACSIN2 phosphomimetic mutant, which does not bind PICK1 efficiently. Taken together, our data demonstrate that the interaction of PICK1 and PACSIN is required for the activity-dependent internalization of AMPARs and for the expression of long-term depression in the cerebellum.

Characterization of IS26-composite transposons and multidrug resistance in conjugative plasmids from Enterobacter cloacae.

SHV-12 is the most widespread resistance determinant of Enterobacter cloacae in Taiwan; however, blaSHV-12 has rarely been mobilized. Six multidrug-resistant E. cloacae isolates were collected. After conjugal transfer, plasmid profiling and analysis of incompatibility groups was performed to characterize the genetic context of blaSHV-12 -containing fragments. The presence of mobile genetic elements was demonstrated by PCR, cloning, sequencing and bioinformatics analyses. Four different ß-lactamase genes (blaTEM-1 , blaSHV-12 , blaCTX-M-3 and/or blaCTX-M-14 ) were observed in the conjugative plasmids belonging to the IncHI2 (n = 4), IncI1 or IncP incompatibility groups. The IS26-blaSHV-12 -IS26 locus was located in five different genetic environments. A novel structural organization of a class 1 integron with the aac(6')-IIc cassette truncated by IS26 was identified in one isolate. Thus, blaSHV-12 was obtained from different plasmids through IS26-mediated homologous recombination. IS26 plays a vital role in the distribution of mobile resistance elements between different plasmids found in multidrug-resistant E. cloacae isolates.

The safety and immunogenicity of a MF59-adjuvanted H5N1 prepandemic influenza vaccine in healthy adults primed with homologous or heterologous H5N1 vaccines: an observational study.

BACKGROUND: World Health Organization (WHO) has recommended individuals with increased risk of contracting influenza A H5N1 infection to be immunized against the virus during the inter-pandemic period. Safety and immunogenicity of H5N1 vaccine among participants primed with homologous or heterologous H5N1 vaccines produced by diverse manufactures have not been reported. METHODS: Healthy individuals aged 20 to 60 years old were recruited and stratified into three groups: participants without priming (control group), participants primed with A/Indonesia/05/2005 vaccine, participants primed with A/Vietnam/1194/2004 vaccine and A/Indonesia/05/2005 vaccine. Enrolled participants received two doses of MF59-adjuvanted A/Vietnam/1194/2004 vaccine (study vaccine). Solicited reactions were recorded by vaccine recipients. Blood samples were obtained for hemagglutination inhibition test. RESULTS: A total of 131 participants were enrolled. No significant adverse events were recorded. Tenderness, fatigue and general muscle ache were the most common solicited reactions which alleviated within one week of immunization. Three weeks after two doses of the study vaccine, 63%, 68% and 88% were in seroprotective status in the control group, A/Indonesia/05/2005 primed group and A/Vietnam/1194/2004 and A/Indonesia/05/2005 primed group, respectively. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 showed high immune response after booster with one dose of the study vaccine. CONCLUSION: The study vaccine did not cause severe adverse events. It elicited mostly mild to moderate reactions among participants. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 vaccine showed higher immune response than those without priming or primed with A/Indonesia/05/2005 vaccine. The report suggested those with an increased risk of influenza A H5N1 virus exposure may benefit from receiving influenza A H5N1 priming during the inter-pandemic period if the antigenicity of the pandemic influenza strain is similar to that of the priming strain.

A rare malignancy of the parotid gland in a 13-year-old Taiwanese boy: case report of a mammary analogue secretory carcinoma of the salivary gland with molecular study.

Mammary analogue secretory carcinoma (MASC) is a recently described malignancy of the salivary glands characterized by an ETV6-NTRK3 (EN) fusion gene. Morphologically, MASC is sometimes difficult to distinguish from acinic cell carcinoma. Consequently, identifying the chromosomal translocation is essential for diagnosis. We present a case of parotid gland MASC in a 13-year-old boy. To the best of our knowledge, this is the youngest case reported in the literature. Histologic evaluation showed a tumor composed of microcysts, tubular structures, solid nests, or papillary architecture, with secretions within the lumens of the cysts or tubules. Immunohistochemically, tumor cells showed diffuse positive staining of S-100 protein, cytokeratin 19, and vimentin. ETV6 rearrangement was detected by fluorescence in situ hybridization and EN fusion transcripts were verified by reverse transcription (RT-PCR) assay.

Comparative Study of the Impurity Effect on SnAgCu and SnZn Solder Joints with Electrodeposited Cu.

Sn-3Ag-0.5Cu (SAC305)- and Sn-9Zn-based alloys (Sn-Zn-X, X = Al, In) are lead-free solders used in the fabrication of solder joints with Cu metallization. Electroplating is a facile technology used to fabricate Cu metallization. However, the addition of functional additive molecules in the plating solution may result in impurity residues in the Cu electroplated layer, causing damage to the solder joints. This study investigates the impurity effect on solder joints constructed by joining various solder alloys to the Cu electroplated layers. Functional additives are formulated to fabricate high-impurity and low-impurity Cu electroplated samples. The as-joined solder joint samples are thermally aged at 120 °C and 170 °C to explore the interfacial reactions between solder alloys and Cu. The results show that the impurity effect on the interfacial reactions between SAC305 and Cu is significant. Voids are massively formed at the SAC305/Cu interface incorporated with a high impurity content, and the Cu6Sn5 intermetallic compound (IMC) grows at a faster rate. In contrast, the growth of the Cu5Zn8 IMC formed in the SnZn-based solder joints is not significantly influenced by the impurity content in the Cu electroplated layers. Voids are not observed in the SnZn-based solder joints regardless of the impurity content, indicative of an insignificant impurity effect. The discrepancy of the impurity effect is rationalized by the differences in the IMC formation and associated atomic interdiffusion in the SAC305- and SnZn-based solder joints.

Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo. Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.

High Prevalence of Carbapenem-Resistant Enterobacterales Producing OXA-48 among Carbapenem-Resistant Isolates in a Regional Hospital in Central Taiwan.

In response to the increasing number of carbapenem-resistant Enterobacterales (CRE), we investigated carbapenemase-producing Klebsiella pneumoniae and non-K. pneumoniae epidemiology and genetics. We collected 76 clinical Enterobacterales and 4 stool surveillance Escherichia coli isolates resistant to ertapenem or imipenem. Using polymerase chain reaction (PCR) and DNA sequencing, we assessed carbapenemases, extended-spectrum ß-lactamases, and AmpC ß-lactamases. Molecular typing via pulsed-field gel electrophoresis (PFGE) and conjugation experiments were conducted to examine resistance gene transfer. Among the 80 isolates, 96.2% harbored at least one carbapenemase gene, with blaOXA-48 in 87.5%. KPC-2 and IMP-8 carbapenemases were found in 15.0 and 22.5% of the isolates, respectively, with 27.5% having 2 or more carbapenemase genes. The PFGE analysis revealed the presence of diverse genotypes. PCR-based plasmid replicon typing identified IncA/C as the most prevalent type among K. pneumoniae isolates (26/29), and IncF and IncFIB among E. coli isolates (22/28). Conjugal transfer was successful for plasmids encoding OXA-48, CTX-M-3, CTX-M-14, CMY-2, and other ß-lactamases, except the KPC-2 gene. In conclusion, our study highlights high carbapenemase prevalence in CRE, primarily OXA-48. Multiple carbapenemases within strains were common, and PFGE showed diverse patterns in these carbapenem-resistant isolates.

Discovery of Dual MER/AXL Kinase Inhibitors as Bifunctional Small Molecules for Inhibiting Tumor Growth and Enhancing Tumor Immune Microenvironment.

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.

Decision Behavior and Influential Factors of Spectacle Prescription for Schoolchildren in Taiwan.

Purpose: The prevalence of children myopia in Taiwan is among the highest in the world. The study aimed to understand the status of the final prescription of the spectacle prescribed by the Taiwan optometrists when they conducted the visual inspection of elementary school, middle school and high school students, and to evaluate the influencing factors of their decision-making behavior. Methods: Among the attendants of the continuing education course activities held by optometrist associations in Taiwan, an anonymous questionnaire survey was given on the spot to optometrists who have passed the national examination. This study received 442 questionnaire surveys, including 174 optometrists and 268 assistant optometrists. The data were analyzed by using chi-square test in IBM SPSS. Results: There are statistically significant differences in the decision-making of spectacle prescription for myopia of -1.00D~-1.50D and -2.25D~-2.50D in the primary school stage between optometrists and assistant optometrists. There are also significant differences for myopia of -2.25D and above in the middle school students. By the time of high school, there are significant differences for myopia from -0.75D to -3.25D and above. The higher the grade, the greater the difference in the final prescription of the spectacles given. As for the judgment factors of the final prescription, only children among elementary school and junior high school show a statistically significant difference in professional judgment between optometrists and assistant optometrists. There is no significant difference in the judgment factors for high school children. Depending on the educational level of optometrists and assistant optometrists and their distribution area, the prescription decisions are also different. Conclusion: The optometrists prefer to prescribe full correction for schoolchildren, while the assistant optometrists mostly prescribe under-correction in prescriptions for low-degree myopia and lower grades. Further investigation is needed to study its impact on children's visual health.

ICA69 regulates activity-dependent synaptic strengthening and learning and memory.

Long-term potentiation (LTP) is one of the major cellular mechanisms for learning and memory. Activity-dependent increases in surface AMPA receptors (AMPARs) are important for enhanced synaptic efficacy during LTP. Here, we report a novel function of a secretory trafficking protein, ICA69, in AMPAR trafficking, synaptic plasticity, and animal cognition. ICA69 is first identified as a diabetes-associated protein well characterized for its function in the biogenesis of secretory vesicles and trafficking of insulin from ER, Golgi to post-Golgi in pancreatic beta cells. In the brain, ICA69 is found in the AMPAR protein complex through its interaction with PICK1, which binds directly to GluA2 or GluA3 AMPAR subunits. Here, we showed that ICA69 regulates PICK1's distribution in neurons and stability in the mouse hippocampus, which in turn can impact AMPAR function in the brain. Biochemical analysis of postsynaptic density (PSD) proteins from hippocampi of mice lacking ICA69 (Ica1 knockout) and their wild-type littermates revealed comparable AMPAR protein levels. Electrophysiological recording and morphological analysis of CA1 pyramidal neurons from Ica1 knockout also showed normal AMPAR-mediated currents and dendrite architecture, indicating that ICA69 does not regulate synaptic AMPAR function and neuron morphology at the basal state. However, genetic deletion of ICA69 in mice selectively impairs NMDA receptor (NMDAR)-dependent LTP but not LTD at Schaffer collateral to CA1 synapses, which correlates with behavioral deficits in tests of spatial and associative learning and memory. Together, we identified a critical and selective role of ICA69 in LTP, linking ICA69-mediated synaptic strengthening to hippocampus-dependent learning and memory.

Significant Hall-Petch effect in micro-nanocrystalline electroplated copper controlled by SPS concentration.

Electroplated Cu has been extensively applied in advanced electronic packaging, and its mechanical properties are critical for reliability. In this study, Cu foils fabricated through electroplating with various bis-(3-sulfopropyl) disulfide (SPS) concentrations are examined using tensile tests. The SPS concentration affects the grain size of the electroplated Cu foils, resulting in different mechanical properties. A significant Hall-Petch effect, [Formula: see text], is demonstrated for the electroplated Cu foils. The different concentrations of impurities identified through time-of-flight secondary ion mass spectrometry correspond to the different grain sizes, determining the transgranular and intergranular fracture during the tensile test. The results demonstrate that the SPS concentration controlling the microstructures of the electroplated Cu results in a Hall-Petch effect on the mechanical properties of the electroplated Cu foils.

Influence of Ring Strain on the Formation of Rearrangement vs Cyclization Isotwistane Products in the Acyl Radical Reaction of Bicyclo[2.2.2]octanone.

An acyl radical reaction of bicyclo[2.2.2]octenone to yield either rearranged or cyclized isotwistane products is described. The influence of ring strain on the reaction was demonstrated by alternating the sizes of the fused ring in the starting material. DFT calculations showed that the reaction is under thermodynamic control and proceeds via a 5-exo-trig cyclization intermediate, which undergoes either hydrogen-atom transfer (HAT) to give a cyclized product or rearrangement via a twistane intermediate to give a rearranged product.