Exploring the synergy between copper electrolytes and molecularly engineered thiocyanate-free cyclometalated ruthenium sensitizers for dye-sensitized solar cells.

Two novel cyclometalated ruthenium complexes, RC-4 and RC-5, featuring 1-phenylisoquinoline and phenyl quinazoline as ancillary ligands, respectively, were synthesized to investigate their viability with the environmentally friendly copper (Cu) redox mediator, [Cu(bpye)2]2+/+. The modification of the ligand environment resulted in variations in the energetics, photophysical properties, and photovoltaic performance of RC-4 and RC-5 sensitizers. Despite RC-5 sensitizer possessing a more positive ground state potential of 1.19 V versus the NHE, the RC-4 sensitizer, with a lower HOMO level of 0.72 V versus NHE, exhibited superior photovoltaic performance along with the Cu electrolyte, attributed to its enhanced light harvesting ability, improved lifetime and reduced back electron transfer, contributing to higher Jsc, Voc, and PCE.

Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants.

Beckwith-Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype. Notably, patients with CDKN1C variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term "CDKN1C Beckwith" to identify 113 cases of patients with molecularly confirmed CDKN1C-BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with CDKN1C-BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with CDKN1C variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations.

Neuroprotective amyloid ß N-terminal peptides differentially alter human α7- and α7ß2-nicotinic acetylcholine (nACh) receptor single-channel properties.

BACKGROUND AND PURPOSE: Oligomeric amyloid ß 1-42 (oAß1-42) exhibits agonist-like action at human α7- and α7ß2-containing nicotinic receptors. The N-terminal amyloid ß1-15 fragment (N-Aß fragment) modulates presynaptic calcium and enhances hippocampal-based synaptic plasticity via α7-containing nicotinic receptors. Further, the N-Aß fragment and its core sequence, the N-amyloid-beta core hexapeptide (N-Aßcore), protect against oAß1-42-associated synapto- and neurotoxicity. Here, we investigated how oAß1-42, the N-Aß fragment, and the N-Aßcore regulate the single-channel properties of α7- and α7ß2-nicotinic receptors. EXPERIMENTAL APPROACH: Single-channel recordings measured the impact of acetylcholine, oAß1-42, the N-Aß fragment, and the N-Aßcore on the unitary properties of human α7- and α7ß2-containing nicotinic receptors expressed in nicotinic-null SH-EP1 cells. Molecular dynamics simulations identified potential sites of interaction between the N-Aß fragment and orthosteric α7+/α7- and α7+/ß2- nicotinic receptor binding interfaces. KEY RESULTS: The N-Aß fragment and N-Aßcore induced α7- and α7ß2-nicotinic receptor single-channel openings. Relative to acetylcholine, oAß1-42 preferentially enhanced α7ß2-nicotinic receptor single-channel open probability and open-dwell times. Co-application with the N-Aßcore neutralized these effects. Further, administration of the N-Aß fragment alone, or in combination with acetylcholine or oAß1-42, selectively enhanced α7-nicotinic receptor open probability and open-dwell times (compared to acetylcholine or oAß1-42). CONCLUSIONS AND IMPLICATIONS: Amyloid-beta peptides demonstrate functional diversity in regulating α7- and α7ß2-nicotinic receptor function, with implications for a wide range of nicotinic receptor-mediated functions in Alzheimer's disease. The effects of these peptides on α7- and/or α7ß2-nicotinic receptors revealed complex interactions with these subtypes, providing novel insights into the neuroprotective actions of amyloid ß-derived fragments against the toxic effects of oAß1-42.

Durability of Vacuum Infusion Tooling Produced from Fused Granular Fabrication Additive Manufacturing.

Fused Granular Fabrication Additive Manufacturing (FGF AM) has the capability to create tooling that is lower cost than conventionally manufactured tooling and still has sufficient properties for many applications. A vacuum infusion (VI) mold was printed from fiberglass-acrylonitrile butadiene styrene (ABS) and evaluated for wear and suitability for small VI runs. The mold was designed to accentuate high wear as a "worst case" scenario. The mold was able to produce 10 parts successfully before any noticeable change occurred to the surface finish. By 14 parts, the surface finish had roughened sufficiently that demolding was difficult and resulted in damage to the part. Profilometry measurements showed a 7 × increase in roughness over the run. No significant tool wear or change in geometry was detected. Even longer life would be expected for typical tooling designs since the test mold was deliberately designed to accentuate wear and demolding issues. Based on these results, similar FGF molds are a feasible option for short run VI production for prototyping or low-volume composites manufacturing, possibly at lower cost and quicker turnaround time than machined aluminum molds.

Publication Rates of Podium Presentations at an Annual Orthopedic Surgery Resident and Fellow Research Symposium.

Introduction Research is an important aspect of residency and fellowship programs across the country. Developing strategies to foster research productivity is worthwhile. An annual research project is one strategy that some programs implement. Methods All resident and fellow (Sports Medicine, Adult Reconstruction, Spine) presentations at an orthopedic surgery department's annual research symposium from June 2016 through June 2021 were identified. Abstract titles, title keywords, and author names were searched in PubMed and Google Scholar to identify the presence of a peer-reviewed publication. Using the total number of research symposium presentations given, the publication rate was calculated for each year, as well as collectively for 2016 to 2021. In addition to publication rate, first author percent, number of citations, Altmetric score, and journal impact factor were recorded. Current PGY-2 through PGY-5 residents completed a survey to assess the perceived value of the annual research symposium. Results Ninety-eight research symposium presentations were reviewed (69 residents, 29 fellows). Forty (58%) resident studies were published and 28 were first-author publications (70%). Thirteen (45%) fellow studies were published and seven were first-author publications (54%). Combining residents and fellows, the overall publication rate was 54% (53/98), and 66% of these (35/53) were first-author publications. There was a wide range of published manuscript journal impact factors, Altmetric scores, and number of citations. All residents surveyed reported finding value in the research symposium. Conclusion The overall publication rate of presentations at an annual orthopedic surgery department research symposium between 2016 and 2021 was 54%, consistent with publication rates reported at National Orthopedic Surgery Society meetings. All residents reported finding value in the annual research symposium. The results of this study support the academic value of implementing a required annual research project and may provide a useful gauge to inform residency and fellowship curricula at other institutions.

A Novel Macroglossia Severity Index for Beckwith-Wiedemann Syndrome.

OBJECTIVE/ SUMMARY BACKGROUND DATA: We propose the first classification scheme for macroglossia in patients with Beckwith-Wiedemann Syndrome (BWS), the BWS Index of macroGlossia (BIG). METHODS: Patients with molecularly confirmed BWS seen from 2004-2023 were included to develop this system. Relationships among BIG scores, tongue reduction surgery, BWS clinical score, percent mosaicism, and polysomnography findings were examined. RESULTS: Patients were classified from BIG0 to BIG3. BIG0 includes those without macroglossia; BIG1 includes those with macroglossia not protruding beyond the teeth/alveolus; BIG2 includes those with tongue protrusion past the teeth/alveolus to the lips but that can be contained within the mouth; and BIG3 includes those with tongues that protrude beyond the teeth/alveolus and lips but that cannot be closed within the mouth. Of the 459 patients with molecularly confirmed BWS, 266 (58.0%) patients were scored. One hundred and eleven (41.7%) were BIG0, 44 (16.5%) were BIG1, 90 (33.8%) were BIG2, and 21 (7.9%) were BIG3. As scores increased, patients had an increased incidence of tongue reduction surgery (BIG0: 0% versus BIG1: 20.5% versus BIG2: 51.1% versus BIG3: 100%; r=0.66, P <0.01). Higher BIG scores were associated with elevated BWS clinical scores (r=0.68, P <0.01) and increased tissue mosaicism (r=0.50, P <0.01) as well as trends towards worse obstructive apnea-hypopnea indices (r=0.29, P =0.02) and lower SpO 2 nadirs (r=-0.29, P =0.02). CONCLUSION: In this large series of patients with Beckwith-Wiedemann Syndrome, increased BIG score correlates with undergoing tongue reduction surgery and increased phenotypic severity. Adoption of the BIG scoring system may facilitate communication and risk stratification across institutions.

Natural Infection of Murraya paniculata and Murraya sumatrana with CLas in Java.

The phloem-limited bacterium, 'Candidatus Liberibacter asiaticus' (CLas), is the putative causal pathogen of the severe Asiatic form of huanglongbing (citrus greening) and is most commonly transmitted by the Asiatic citrus psyllid (ACP), Diaphorina citri. CLas severely affects many Citrus species and hybrids and has been recorded in the Citrus relative, orange jasmine, Murraya paniculata (L.) Jack (syn. M. exotica L.). In this study, 13 accessions of three Murraya species (M. paniculata, M. sumatrana Roxb. and M. lucida (G.Forst.) Mabb,) and the Papuan form of a putative hybrid (M. omphalocarpa Hayata) were identified morphologically and molecularly based on sequence identity of the matK-5'trnK region of the chloroplast genome, and infection on these plants under field conditions was determined by PCR and qPCR on 2-4 occasions over 14 months. CLas was repeatedly detected in leaflet midribs by PCR and qPCR on four and three accessions of M. paniculata and M. sumatrana, respectively. It was not detected in leaflet midribs of single accessions of M. lucida and M. omphalocarpa. The species identification of the CLas-positive accessions was further confirmed using all the molecular taxonomic markers consisting of the six fragments of the maternally inherited chloroplast genome and part of the nuclear-encoded ITS region. The results indicated that natural infection of M. paniculata and M. sumatrana with CLas can occur in Java. This is the first demonstration of the natural infection of M. sumatrana with CLas. Further studies are required to determine if infections persist in the absence of D. citri.

Post-operative protein supplementation following orthopaedic surgery: A systematic review.

Decreased mechanical loading after orthopaedic surgery predisposes patients to develop muscle atrophy. The purpose of this review was to assess whether the evidence supports oral protein supplementation can help decrease postoperative muscle atrophy and/or improve patient outcomes following orthopaedic surgery. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). PubMed (MEDLINE), Embase, Scopus, and Web of Science were searched for randomized controlled trials that assessed protein or amino acid supplementation in patients undergoing orthopaedic surgery. Two investigators independently conducted the search using relevant Boolean operations. Primary outcomes included functional or physiologic measures of muscle atrophy or strength. Fourteen studies including 611 patients (224 males, 387 females) were analyzed. Three studies evaluated protein supplementation after ACL reconstruction (ACLR), 3 after total hip arthroplasty (THA), 5 after total knee arthroplasty (TKA), and 3 after surgical treatment of hip fracture. Protein supplementation showed beneficial effects across all types of surgery. The primary benefit was a decrease in muscle atrophy compared to placebo as measured by muscle cross sectional area. Multiple authors also demonstrated improved functional measures and quicker achievement of rehabilitation benchmarks. Protein supplementation has beneficial effects on mitigating muscle atrophy in the postoperative period following ACLR, THA, TKA, and surgical treatment of hip fracture. These effects often correlate with improved functional measures and quicker achievement of rehabilitation benchmarks. Further research is needed to evaluate long-term effects of protein supplementation and to establish standardized population-specific regimens that maximize treatment efficacy in the postoperative period.

Rehabilitation and return to sport criteria following surgical treatment of osteochondritis dissecans of the capitellum: a systematic review.

Background: Osteochondritis dissecans (OCD) of the capitellum is a well-described condition that most commonly affects adolescent throwing athletes and gymnasts. There is no gold standard rehabilitation protocol or timing for return to sport (RTS) after surgical management of OCD of the capitellum. Hypothesis/Purpose: The purpose of the study was to identify in the existing literature any criteria used for RTS following surgical treatment of OCD of the capitellum. The hypothesis was that surgeons would utilize length of time rather than functional criteria or performance benchmarks for RTS. Methods: Level 1 to 4 studies evaluating athletes who underwent surgery for OCD of the capitellum with a minimum follow-up of 1-year were included. Studies not describing RTS criteria, including less than 1-year follow-up, non-operative management only, and revision procedures were excluded. Each study was analyzed for RTS criteria, RTS rate, RTS timeline, sport played, level of competition, graft source (if utilized), and postoperative rehabilitation parameters. Assessment of bias and methodological quality was performed using the Coleman methodology score and RTS value assessment. Results: All studies reported a rehabilitation protocol with immobilization followed by bracing with progressive range of motion. RTS rate was 80.9% (233/288). The majority of studies reported using time-based criteria for RTS (11/15). The most commonly reported timeline was 6 months (range: 3-12 months). Conclusion: The overall RTS rate after surgical treatment of capitellar OCD is high with no consensus on RTS criteria. The two most consistent RTS criteria reported in the literature are return of elbow range of motion and healing demonstrated on postoperative imaging. There is a wide range of time to RTS in the literature, which may be sport dependent. Further research is needed to develop functional and performance-based metrics to better standardize RTS criteria and rehabilitation protocols.

Analogs of α-conotoxin PnIC selectively inhibit α7ß2- over α7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism.

This study was undertaken to identify and characterize the first ligands capable of selectively identifying nicotinic acetylcholine receptors containing α7 and ß2 subunits (α7ß2-nAChR subtype). Basal forebrain cholinergic neurons express α7ß2-nAChR. Here, they appear to mediate neuronal dysfunction induced by the elevated levels of oligomeric amyloid-ß associated with early Alzheimer's disease. Additional work indicates that α7ß2-nAChR are expressed across several further critically important cholinergic and GABAergic neuronal circuits within the central nervous system. Further studies, however, are significantly hindered by the inability of currently available ligands to distinguish heteromeric α7ß2-nAChR from the closely related and more widespread homomeric α7-only-nAChR subtype. Functional screening using two-electrode voltage-clamp electrophysiology identified a family of α7ß2-nAChR-selective analogs of α-conotoxin PnIC (α-CtxPnIC). A combined electrophysiology, functional kinetics, site-directed mutagenesis, and molecular dynamics approach was used to further characterize the α7ß2-nAChR selectivity and site of action of these α-CtxPnIC analogs. We determined that α7ß2-nAChR selectivity of α-CtxPnIC analogs arises from interactions at a site distinct from the orthosteric agonist-binding site shared between α7ß2- and α7-only-nAChR. As numerous previously identified α-Ctx ligands are competitive antagonists of orthosteric agonist-binding sites, this study profoundly expands the scope of use of α-Ctx ligands (which have already provided important nAChR research and translational breakthroughs). More immediately, analogs of α-CtxPnIC promise to enable, for the first time, both comprehensive mapping of the distribution of α7ß2-nAChR and detailed investigations of their physiological roles.

Infection with 'Candidatus Liberibacter asiaticus' improves the fecundity of Diaphorina citri aiding its proliferation: A win-win strategy.

The evolution of insect vector-pathogen relationships has long been of interest in the field of molecular ecology. One system of special relevance, due to its economic impacts, is that between Diaphorina citri and 'Candidatus Liberibacter asiaticus' (CLas), the cause of the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts, boosting opportunities for pathogens to acquire new vector hosts. The molecular mechanism behind this life-history shift remains unclear. Here, we found that CLas promoted ovarian development and increased the expression of the vitellogenin receptor (DcVgR) in ovaries. DcVgR RNAi significantly decreased fecundity and CLas titer in ovaries, extended the preoviposition period, shortened the oviposition period and blocked ovarian development. Given their importance in gene regulation, we explored the role of miRNAs in shaping these phenotypes and their molecular triggers. Our results showed that one miRNA, miR-275, suppressed DcVgR expression by binding to its 3' UTR. Overexpression of miR-275 knocked down DcVgR expression and CLas titer in ovaries, causing reproductive defects that mimicked DcVgR knockdown phenotypes. We focused, further, on roles of the Juvenile Hormone (JH) pathway in shaping the observed fecundity phenotype, given its known impacts on ovarian development. After CLas infection, this pathway was upregulated, thereby increasing DcVgR expression. From these combined results, we conclude that CLas hijacks the JH signalling pathway and miR-275, thereby targeting DcVgR to increase D. citri fecundity. These changes simultaneously increase CLas replication, suggesting a pathogen-vector host mutualism, or a seemingly helpful, but cryptically costly life-history manipulation.

Lower reproductive rates of Asian citrus psyllid (Hemiptera: Psyllidae) on 'Tahiti' acid lime than on 'Valencia' sweet orange

ABSTRACT The 'Tahiti' acid lime and orange trees are hosts of 'Candidatus Liberibacter asiaticus' (CLas), the pathogen associated with the severe Asian form of huanglongbing (HLB), the most devasting citrus disease. They are also hosts of the vector of CLas, the Asian citrus psyllid (ACP) Diaphorina citri Kuwayama. Relatively small numbers of lime trees occur in gardens and small orchards near large commercial 'Valencia' sweet orange orchards in Brazil. Applications of insecticides to suppress populations of ACP on the lime trees are usually nil or less frequent than in the orange orchards. Abundance of the psyllid on lime trees may therefore increase the risk of CLas spreading to the orchards. Because the abundance of the psyllid is influenced by the suitability of the trees as hosts, we compared reproductive potential of the insect on the two hosts in a controlled environment chamber (CEC) and in a greenhouse (GH). Daily temperature and relative humidity averaged 22ºC and 60% inside the CEC and 24°C and 70% inside the GH. Two pairs of adult male and female psyllids were caged for 3 days on new shoots and the fecundity and durations of development and survival of eggs and nymphs evaluated. Overall, acid 'Tahiti' was 3.5 times less suitable to ACP than 'Valencia'. Fecundity and survival of nymphs were 27% and 59% lower, and the life cycle 34% longer on 'Tahiti' than on 'Valencia'. Potential impacts of the results on CLas spread and HLB control are discussed.

Nano-plastics and gastric health: Decoding the cytotoxic mechanisms of polystyrene nano-plastics size.

Gastrointestinal diseases exert a profound impact on global health, leading to millions of healthcare interventions and a significant number of fatalities annually. This, coupled with escalating healthcare expenditures, underscores the need for identifying and addressing potential exacerbating factors. One emerging concern is the pervasive presence of microplastics and nano-plastics in the environment, largely attributed to the indiscriminate usage of disposable plastic items. These nano-plastics, having infiltrated our food chain, pose a potential threat to gastrointestinal health. To understand this better, we co-cultured human gastric fibroblasts (HGF) with polystyrene nano-plastics (PS-NPs) of diverse sizes (80, 500, 650 nm) and meticulously investigated their cellular responses over a 24-hour period. Our findings revealed PS particles were ingested by the cells, with a notable increase in ingestion as the particle size decreased. The cellular death induced by these PS particles, encompassing both apoptosis and necrosis, showcased a clear dependence on both the particle size and its concentration. Notably, the larger PS particles manifested more potent cytotoxic effects. Further analysis indicated a concerning reduction in cellular membrane potential, alongside a marked increase in ROS levels upon PS particles exposure. This suggests a significant disruption of mitochondrial function and heightened oxidative stress. The larger PS particles were especially detrimental in causing mitochondrial dysfunction. In-depth exploration into the PS particles impact on genes linked with the permeability transition pore (PTP) elucidated that these PS particles instigated an internal calcium rush. This surge led to a compromise in the mitochondrial membrane potential, which in tandem with raised ROS levels, further catalyzed DNA damage and initiated cell death pathways. In essence, this study unveils the intricate mechanisms underpinning cell death caused by PS particles in gastric epithelial cells and highlighting the implications of PS particles on gastrointestinal health. The revelations from this research bear significant potential to shape future healthcare strategies and inform pertinent environmental policies.

Unraveling the threat: Microplastics and nano-plastics' impact on reproductive viability across ecosystems.

Plastic pollution pervades both marine and terrestrial ecosystems, fragmenting over time into microplastics (MPs) and nano-plastics (NPs). These particles infiltrate organisms via ingestion, inhalation, and dermal absorption, predominantly through the trophic interactions. This review elucidated the impacts of MPs/NPs on the reproductive viability of various species. MPs/NPs lead to reduced reproduction rates, abnormal larval development and increased mortality in aquatic invertebrates. Microplastics cause hormone secretion disorders and gonadal tissue damage in fish. In addition, the fertilization rate of eggs is reduced, and the larval deformity rate and mortality rate are increased. Male mammals exposed to MPs/NPs exhibit testicular anomalies, compromised sperm health, endocrine disturbances, oxidative stress, inflammation, and granulocyte apoptosis. In female mammals, including humans, exposure culminates in ovarian and uterine deformities, endocrine imbalances, oxidative stress, inflammation, granulosa cell apoptosis, and tissue fibrogenesis. Rodent offspring exposed to MPs experience increased mortality rates, while survivors display metabolic perturbations, reproductive anomalies, and weakened immunity. These challenges are intrinsically linked to the transgenerational conveyance of MPs. The ubiquity of MPs/NPs threatens biodiversity and, crucially, jeopardizes human reproductive health. The current findings underscore the exigency for comprehensive research and proactive interventions to ameliorate the implications of these pollutants.

All-Arthroscopic Treatment of Off-Track Hill-Sachs Lesions Using Fresh Osteochondral Allograft Plugs: "Rocks in a Stream".

Osteochondral allograft transplantation is a well-described technique for the treatment of large, engaging Hill-Sachs lesions. Traditionally, osteochondral allografts are size-matched to the defect, which can be expensive and time-consuming, and the majority of described techniques require an open approach. This Technical Note describes an all-arthroscopic approach to Hill-Sachs osteochondral allograft transplantation using premade osteochondral allograft plugs, eliminating the need for size-matching and graft harvest. This approach works not by anatomically filling the defect, but rather by bridging the defect to prevent it from engaging the glenoid.

Preclinical Synergistic Combination Therapy of Lurbinectedin with Irinotecan and 5-Fluorouracil in Pancreatic Cancer.

Pancreatic cancer is a devastating disease with a poor prognosis. Novel chemotherapeutics in pancreatic cancer have shown limited success, illustrating the urgent need for new treatments. Lurbinectedin (PM01183; LY-01017) received FDA approval in 2020 for metastatic small cell lung cancer on or after platinum-based chemotherapy and is currently undergoing clinical trials in a variety of tumor types. Lurbinectedin stalls and degrades RNA Polymerase II and introduces breaks in DNA, causing subsequent apoptosis. We now demonstrate lurbinectedin's highly efficient killing of human-derived pancreatic tumor cell lines PANC-1, BxPC-3, and HPAF-II as a single agent. We further demonstrate that a combination of lurbinectedin and irinotecan, a topoisomerase I inhibitor with FDA approval for advanced pancreatic cancer, results in the synergistic killing of pancreatic tumor cells. Western blot analysis of combination therapy indicates an upregulation of γH2AX, a DNA damage marker, and the Chk1/ATR pathway, which is involved in replicative stress and DNA damage response. We further demonstrate that the triple combination between lurbinectedin, irinotecan, and 5-fluorouracil (5-FU) results in a highly efficient killing of tumor cells. Our results are developing insights regarding molecular mechanisms underlying the therapeutic efficacy of a novel combination drug treatment for pancreatic cancer.