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Etsuo Chihara, Tomoyuki Chihara Sensho-kai Eye Institute, Kyoto, 611-0043, JapanCorrespondence: Etsuo Chihara, Sensho-kai Eye Institute, Minamiyama 50-1, Iseda, Uji, Kyoto, 611-0043, Japan, Tel +81-774-45-2060, Fax +81-774-45-4565, Email chiha492001@gmail.comPurpose: We introduce a newly designed T-shaped internal trabeculotomy hook and compare its surgical outcomes with those of Kahook dual blade (KDB) surgery.Patients and Methods: One eye each of seventeen and sixty-one patients underwent T-hook and KDB surgeries, respectively. Post-surgical intraocular pressure (IOP), medications, visual acuity, and prevalence of IOP spikes and hyphema were compared between the two cohorts.Results: The utility of the T-hook was excellent and enabled the easy opening of the Schlemm’s canal. The pre-surgical IOP of 25.6 ± 7.5 mmHg in the T-hook cohort decreased to 14.1 ± 4.3 (− 41.2% reduction) and 15.0 ± 3.1mmHg (− 39.3% reduction) at 3 (P< 0.001) and 6 months (P=0.003), respectively. Pre-surgical medications of 2.8 decreased to 2.3 and 2.0 medications, respectively, at 3 and 6 months. The best-corrected visual acuity (BCVA) improved from the pre-surgical logarithm of the minimum angle resolution (logMAR) of 0.148 to − 0.012 at three months (P=0.036,). While the pre-surgical IOP of 24.9± 4.3 mmHg in the KDB cohort decreased to 16.5± 5.7 mmHg (− 35.5%, P< 0.001) and 16.1± 3.4 mmHg (− 33.5%, P< 0.001) at 3 and 6 months, respectively. Reduction in medications at 3- and 12-month timepoints (from 2.8 to 1.7 and 1.7, respectively; P< 0.001) and improvement in BCVA at three months (from 0.106 to − 0.025 logMAR, P< 0.001) were also significant. There was no difference between the T-hook and KDB cohorts in terms of the pre-surgical IOP (P=0.15) and post-surgical IOP at 1 (P=0.27), 3 (P=0.17), 6 (P=0.47), and 12 months (P=0.11, Mann–Whitney U-test). The prevalence of a post-surgical IOP spike in the T-hook and KDB cohorts was 41.2% and 47.5%, and that of post-surgical hyphema was 17.6% and 26.2%, respectively.Conclusion: The novel T-hook was easy to use and was as useful as the KDB device in performing internal trabeculotomy.Keywords: minimally invasive glaucoma surgery, MIGS, trabecular meshwork, nonpenetrating glaucoma surgery, Schlemm’s canal, double mirror gonio lens, T-hook

AIM: To explore the clinical efficacy of the T-hook pre-chopping combined with capsule fine treatment technology for patients with high myopia and cataract.METHODS: From March 2016 to February 2019, 56 cases(80 eyes)of cataract patients with high myopia were treated in cataract department of Hebei Province Eye Hospital. They were randomly divided into A and B groups, 40 eyes in each group. Group A underwent T-hook pre-chopping combined with fine capsular treatment. Cataract phacoemulsification combined with intraocular lens implantation was purely performed in group B. We compared the cumulative release energy of ultrasound during operation between the two groups. We also observed the best corrected visual acuity(BCVA), the amount of contraction of the anterior capsule, the degree of posterior capsule opacification, intraocular lens neutrality and complications for more than 6mo.RESULTS: The cumulative release energy of ultrasound in group A was less than that in group B(12.23±3.61 vs 20.46±4.61, PZ=5.328, P=0.002). The changes of anterior capsular contraction and intraocular lens decentration(0.18±0.14, 0.02±0.007mm)were less than those of group B(0.82±0.23, 0.65±0.240mm)(PCONCLUSION: We used T-hook pre-chopping combined with capsule fine treatment technology to treat cataract with high myopia, which could reduce the use of ultrasound energy during operation, reduce the risk of posterior capsule rupture, effectively avoid the occurrence of posterior cataract, and achieve satisfactory clinical effect.

Abstract Background A variety of surgical techniques had been developed over the past few decades for treating thumb carpometacarpal joint (CMCJ) osteoarthritis (OA). However, there are currently no accepted consensus on the ideal treatment for thumb CMCJ OA. Arthrodesis was one of the widely popular treatment methods; however, studies have showed that non-union rates were as high as 50%, with higher complications such as osteoarthritis of neighbouring joints and higher revision surgeries required as compared to other surgical methods. Patients with arthrodesis were also reported to have decreased thumb range of motion and loss of opponens function. Currently, there are numerous intraoperative positioning techniques for arthrodesis which could be confusing for young surgeons. With recent developments of fixation plates and better understanding of the wrist anatomy, this retrospective review aimed to evaluate the efficacy of our intraoperative hand-grip positioning method for arthrodesis of thumb CMCJ OA. What are the postoperative functional outcomes of (1) T-hook plates and (2) our intraoperative hand-grip positioning method for Eaton III thumb CMCJ OA arthrodesis by evaluating pain visual analogue scale (VAS) score, Disabilities of the Arm, Shoulder and Hand questionnaires (DASH), Mayo Wrist scores, capability of thumb opposition (Kapandji score), and comparing pre- and postoperative grip and pinch strength? Methods Twenty patients with CMCJ OA underwent arthrodesis using our intraoperative hand-grip positioning method and T-hook plates and screws (Acumed, USA). Patients were evaluated preoperatively and at 1, 3, 6 and 12 months postoperatively. Radiologic assessment including fusion evaluation, evaluation of radial and palmar abduction angles was done on hand X-rays. Results Twenty patients with a minimum follow-up duration of 12 months were included in this study. 100% fusion rate was achieved with only 1 case of complication involving radial sensory nerve neuropathy which was resolved after removal of implant and neurolysis. Significant improvement in pain and Mayo Wrist scores were noted 3 months postoperatively, whilst DASH score exhibited significant improvements after 6 months of follow-up (p

Background Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 such as T20 (Enfuvirtide) and C34 are potent viral fusion inhibitors. We have recently found that two Nterminal residues (Met115 and Thr116) of CHR peptides form a unique M-T hook structure that can greatly enhance the binding and anti-HIV activity of inhibitors. Here, we applied two M-T hook residues to optimize SC29EK, an electrostatically constrained peptide inhibitor with a potent anti-HIV activity. Results The resulting peptide MT-SC29EK showed a dramatically increased binding affinity and could block the six-helical bundle (6-HB) formation more efficiently. As expected, MTSC29EK potently inhibited HIV-1 entry and infection, especially against those T20- and SC29EK-resistant HIV-1 variants. More importantly, MT-SC29EK and its short form (MT SC22EK) suffered from the difficulty to induce HIV-1 resistance during the in vitro selection, suggesting their high genetic barriers to the development of resistance. Conclusions Our studies have verified the M-T hook structure as a vital strategy to design novel HIV-1 fusion inhibitors and offered an ideal candidate for clinical development. [ABSTRACT FROM AUTHOR]

CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal heptad repeat of gp41. We recently identified that its N-terminal residues Met-626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus stabilizing the interaction of the inhibitor with the deep pocket on the N-terminal heptad repeat. In this study, we further demonstrated that the M-T hook structure is a key determinant of CP621-652 in terms of its thermostability and anti-HIV activity. To directly define the structure and function of the M-T hook, we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution crystal structure (1.9 Å) of MT-C34 complexed by an N-terminal heptad repeat-derived peptide reveals that the M-T hook conformation is well preserved at the N-terminal extreme of the inhibitor. Strikingly, addition of two hook residues could dramatically enhance the binding affinity and thermostability of 6-helix bundle core. Compared with C34, MT-C34 exhibited significantly increased activity to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5-fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher increase than C34 in blocking 6-helix bundle formation. We further showed that MT-C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1 variants. Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors. [ABSTRACT FROM AUTHOR]

Aim: We previously designed an artificial HIV-1 fusion inhibitor, PBDtrp-m4HR. Here, we have added two amino acid residues that can form an M-T hook structure at its N-terminus, with the aim of improving its antiviral potency and drug-resistance profile. Methods: Peptides were synthesized and tested for their inhibitory activity on HIV-1 Env-mediated cell-cell fusion and infection by HIV-1 strains, including those resistant to T2635, the third generation HIV fusion inhibitor, as well as its binding affinity to the gp41 NHR-peptide N36. Results: MT-PBDtrp-m4HR exhibited improved inhibitory activity on HIV-1 infection and Env-mediated cell-cell fusion, displayed an improved drug-resistance profile and increased NHR-binding affinity. Conclusion: The added M-T hook is able to enhance or stabilize the interaction between MT-PBDtrp-m4HR and the viral gp41 NHR domain. Therefore, MT-PBDtrp-m4HR has potential to be further developed as a new HIV fusion inhibitor. The approach described in this study can also be used for designing artificial peptides against other enveloped viruses with class I membrane fusion proteins. [ABSTRACT FROM AUTHOR]

Peptides derived from the C-terminal heptad repeat (C peptides) of HIV-1 gp41 are potent inhibitors against virus entry. However, development of a short C peptide possessing high anti-HIV potency is considered a daunting challenge. We recently discovered that the residues Met626 and Thr627 preceding the pocket-binding domain of the C peptide adopt a unique M-T hook structure that is crucial for the design of HIV-1 fusion inhibitors. In this study, we first presented a proof-of-concept prototype that the M-T hook residues can dramatically improve the antiviral activity and thermostability of a short C peptide. We then generated a 24-mer peptide termed MT-SC22EK by incorporating the M-T hook structure to the N terminus of the poorly active short C peptide SC22EK. Amazingly, MT-SC22EK inhibited HIV-1-mediated cell fusion and infection at a level comparable to C34, T1249, SC29EK, and sifuvirtide, and it was highly active against diverse HIV-1 subtypes and variants, including those T20 (enfuvirtide) and SC29EK-resistant viruses. The high-resolution crystal structure of MTSC22EK reveals the N-terminal M-T hook conformation folded by incorporated Met626 and Thr627 and identifies the C-terminal boundary critical for the anti-HIV activity. Collectively, our studies provide new insights into the mechanisms of HIV-1 fusion and its inhibition. [ABSTRACT FROM AUTHOR]

EBV (Epstein-Barr Virus) and other human DNA viruses are associated with autoimmune syndromes in epidemiologic studies. In this work, immunoglobulin G response to EBV-encoded proteins which share regions with human immune response proteins from the human host including ZEBRA (BZLF-1 encoded protein), BALF-2 recombinase expressed primarily during the viral lytic replication cycle, and EBNA-1 (Epstein-Barr Virus Nuclear Antigen) expressed during the viral latency cycle respectively were characterized using a laser-printed micro-array (PEPperprint.com). IgG response to conserved "A/T hooks" in EBV-encoded proteins such as EBNA-1 and the BALF-2 recombinase related to host DNA-binding proteins including RAG-1 recombinase and histones, and EBV-encoded virokines such as the IL-10 homologue BCRF-1 suggest further directions for clinical research. The author suggests that proteomic "molecular fingerprints" of the immune response to viral proteins shared with human immune response genes are potentially useful in early diagnosis and monitoring of autoantibody production and response to therapy in EBV-related autoimmune syndromes. [ABSTRACT FROM AUTHOR]

Let $p_t(a,b;n)$ denote the number of partitions of n such that the number of t -hooks is congruent to $a \bmod {b}$. For $t\in \{2, 3\}$ , arithmetic progressions $r_1 \bmod {m_1}$ and $r_2 \bmod {m_2}$ on which $p_t(r_1,m_1; m_2 n + r_2)$ vanishes were established in recent work by Bringmann, Craig, Males and Ono ['Distributions on partitions arising from Hilbert schemes and hook lengths', Forum Math. Sigma 10 (2022), Article no. e49] using the theory of modular forms. Here we offer a direct combinatorial proof of this result using abaci and the theory of t -cores and t -quotients. [ABSTRACT FROM AUTHOR]

Wafer‐scale deposition of high‐휅 gate dielectrics compatible with atomically thin van der Waals layered semiconductors (e.g., MoS2, WS2, WSe2) is urgently needed for practical applications of field effect transistors based on 2D materials. A study on a high‐휅 molecular crystal antimony trioxide (Sb2O3) gate dielectric examined the role of electrode material on dielectric degradation and breakdown. It is demonstrated that the thin films of Sb2O3 can be uniformly deposited on a wafer scale. The current–voltage (I–V) curves show tightly controlled distributions of both leakage current and breakdown voltage. Electrical measurements reveal that defects are generated gradually upon electrical stressing. The evaluation of degradation is based on charge trapping, stress‐induced leakage current, and dielectric breakdown measurements. The breakdown voltage distribution follows a tight monomodal Weibull distribution suggesting a high quality of the film. Comparing Ti and Au as gate electrodes, both the breakdown field and the tunnel current are affected by the choice of electrode material. Transmission electron microscopy reveals that the chemistry at the electrode/Sb2O3 interface plays an important role and that Ti scavenges oxygen from the Sb2O3, forming a defective oxide layer at the Ti/Sb2O3 interface. For the Au electrode, this interfacial reaction is completely absent, improving the dielectric performance. [ABSTRACT FROM AUTHOR]

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages, including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In the quest for effective HIV vaccines, discovering potent antigens and designing suitable vaccine strategies are crucial for overcoming challenges such as low immunogenicity, safety concerns, and increased viral load. Innovative strategies for vaccine development through peptide research are, therefore, a key focus area for achieving effective HIV prevention. This review aims to explore the strategies for designing peptides with anti-HIV activity and to highlight their role in advancing both therapeutic and preventive measures against HIV. [ABSTRACT FROM AUTHOR]

This study investigates global extreme precipitation events (EPEs) during warm seasons, with a particular focus on EPEs preceded by extreme heat stress (EPE-Hs) and a comparative analysis with those not (EPE-NHs). Using reanalysis product and Earth System Model data, the spatiotemporal characteristics and temperature sensitivities of EPEs are analyzed. Results show that EPE-Hs, while less frequent, have longer duration and greater magnitude compared to EPE-NHs, particularly in high latitude regions. In the future, a significant increase is projected in the characteristics of EPE-Hs, in contrast to the stable duration and magnitude of EPE-NHs. EPE-Hs demonstrate substantially higher temperature sensitivity than EPE-NHs, especially in low latitudes. The precipitation-temperature scaling relationships diverge markedly between EPE-Hs and EPE-NHs, with notable regional variations. These insights are pivotal for crafting region-specific early warning and adaptation strategies to mitigate the risks associated with extreme precipitation under the backdrop of global warming. [ABSTRACT FROM AUTHOR]

In recent years, transdermal drug delivery systems have gained considerable attention for their ability to enhance patient compliance and provide consistent drug release. However, the barrier function of the skin's outermost layer remains the foremost challenge in these systems. As a result, there is a growing interest in the use of ethosomes as a cutting-edge nanocarrier in drug delivery. This review presents the concept and mechanism of action of ethosomes as well as the numerous types and preparation techniques available. It also discusses the significance of characterization methods and how they impact ethosomal properties along with recent advancements and applications in the realm of transdermal drug delivery. Ethosomes exhibit tremendous potential for the pharmaceutical industry, and optimizing preparation methods, performing comprehensive property studies, and exploring their applications are critical areas for future research. [ABSTRACT FROM AUTHOR]

In the global public health discourse, involving men in maternal and neonatal health is regarded as crucial for positive outcomes in both health and development. In South Africa, health interventions designed to promote male partner involvement among low-income indigenous populations have been framed within social constructivist notions of masculinities and have produced mixed outcomes. This has necessitated calls to explore alternative approaches, including the need to decolonise men and masculinities studies in Africa. As part of one phase of formative research for a mixed-method project aimed at adapting a male involvement intervention for the context of Sesotho-speaking men and women in the Free State, we applied a multi-site case study research design and collected qualitative data using focus group discussions and key informant interviews. Verbatim-recorded transcripts were translated, transcribed, and thematically analysed with NVIVO 14. The results indicate that customary practices in pregnancy, delivery, and newborn care are not static and vary between families based on belief systems, socioeconomic status, geographical setting (peri-urban/rural), and kinship networks of care. Therefore, these practices and beliefs should be understood, affirmed, and contested within the complex African-centred material and immaterial worldviews on personhood in which they were generated, transmitted, rejected, or adopted. It is recommended that a decolonised approach to male partner involvement in this context must be cognisant of the intersections of racial and gendered power relations, contestations in beliefs and practices, the resilient effect of colonialism on indigenous gender systems, as well as contemporary global entanglements that inform North–South power relations on the best practices in maternal and newborn health in the public health sector in South Africa. [ABSTRACT FROM AUTHOR]

Africa began implementing the Sustainable Development Goals (SDGs) in 2015 emphasizing on sustainable management and effective use of natural capital to spur economic growth (Goals 12, 14, and 15). This study using World Bank data sets from 46 African countries selected for the years 2000 to 2022, examined the nexus between natural resource endowments and economic growth in Africa. We used the system generalized method of moments (sys-GMM) and dynamic panel threshold regression (DPTR) to analyze the data. The findings of the two-step sys-GMM estimation using 'xtabond2' revealed that when the institutional quality variable is added and excluded from the model, natural resource dependence negatively impacts economic growth, but the impact is greater when the institution is excluded. In the estimation of the interaction variable of natural resource dependence and institutional variable included in the model, natural resource dependence positively impacts economic growth. The results of the DPTR using "xthenreg" showed that when the threshold value of natural resource dependence is ≤ 1.73% of gross domestic product, natural resource dependence has a positive impact on economic growth and a negative impact when the threshold value is above 1.73%. Similarly, when the institutional quality threshold is ≤ 0.277, natural resources dependence impacts economic growth negatively; above the threshold (0.277), the impact is positive. In conclusion, natural resource endowment is a curse with no or low-quality institutions and a blessing with high-quality institutions. Thus, building strong institutions and proper utilization of natural resources helps to minimize the adverse impact of resource endowments on economic growth. [ABSTRACT FROM AUTHOR]

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies. [ABSTRACT FROM AUTHOR]

Background: One of the primary flavonoids found in the Glycyrrhiza glabra is called glabridin, which has anti-inflammatory, anti-bacterial, and antineoplastic effects. However, the insolubility of glabridin in water limits its application. Liposomes can increase the solubility of insoluble drugs and improve their bioavailability. Objectives: We examined the potential for the treatment of glabridin liposomes on histamine-induced atopic dermatitis. Materials and Methods: After GL treatment, histopathology, inflammatory cytokines, and atopic dermatitis-related proteins were used to evaluate the therapeutic effect of GL. Results: Glabridin liposomes alleviated histamine-induced scratching behavior; reduced mast cell proliferation, infiltration, and degranulation; and restrained the expression of associated pro-inflammatory cytokines. Additionally, glabridin liposomes restored nerve growth factor to normal levels and enhanced the expression of filaggrin to promote cuticle growth and repair skin damage caused by atopic dermatitis. Conclusion: Glabridin liposomes may relieve histamine-induced skin hypersensitivity and cortical hyperplasia by inhibiting the production of inflammatory cytokines, demonstrating their potential for the clinical treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Chitosan is the most commonly investigated functional cationic biopolymer in a wide range of medical applications due to its promising properties such as biocompatibility, biodegradability, and bioadhesivity, as well as its numerous bioactive properties. Within the last three decades, chitosan and its derivatives have been investigated as biomaterials for drug and vaccine delivery systems, besides for their bioactive properties. Due to the functional groups in its structure, it is possible to tailor the delivery systems with desired properties. There has been a great interest in the application of chitosan-based systems also for the prevention and treatment of infectious diseases, specifically due to their antimicrobial, antiviral, and immunostimulatory effects. In this review, recent applications of chitosan in the prevention and treatment of infectious diseases are reviewed, and possibilities and limitations with regards to technical and regulatory aspects are discussed. Finally, the future perspectives on utilization of chitosan as a biomaterial are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: HIV-1 is a hard-to-eradicate persisting infection which, despite the current antiretroviral therapy, takes about 600,000 human lives every year. HIV-1 uses the CD4 receptor and co-receptors CCR5 or CXCR4 on the surfaces of T cells, macrophages, and dendritic cells to enter the host immune cells. Inhibition of HIV-1 entry is one of the most effective approaches for blocking viral infection. Creating genetically engineered cells that are insensitive to HIV-1 entry is a promising instrument for virus eradication. We previously showed that knock-in-based expression of the fusion inhibitory peptides MT-C34 or 2P23 fully protected primary CD4 human T lymphocytes from HIV-1 infection. Here, we generated and characterized a novel human chimeric antibody against the MT-C34 peptide with the ability to mediate antibody-dependent cell cytotoxicity (ADCC). The created antibody is a useful supplementary reagent for the detection and enrichment of engineered HIV-1-resistant cells developed for research studies or clinical applications. Its ADCC activity can potentially be used for subsequent elimination of engineered malignancy-prone T and CAR cells in vivo, but the efficacy and limitations of in vivo antibody application should be determined further. Peptides from heptad repeat (HR1 and HR2) regions of gp41 are effective inhibitors of HIV-1 entry that block the fusion of viral and cellular membranes, but the generation of antibodies highly specific for these peptides is challenging. We have previously described a mouse hybridoma that recognizes MT-C34-related peptides derived from HR2. It was used for the selection of HIV-1-resistant CD4 lymphocytes engineered to express the MT-C34 peptide via a CRISPR/Cas9-mediated knock-in into the CXCR4 locus. In this study, we cloned variable domains of this antibody and generated a recombinant chimeric antibody (chAb) by combining it with the constant regions of the humanized antibody Trastuzumab. The new chAb displayed a high specificity and two-fold higher level of affinity than the parental mouse monoclonal antibody. In addition, chAb mediated up to 27–43% of the antibody-dependent cellular cytotoxicity towards cells expressing MT-C34 on their surface. The anti-MT-C34 chAb can be easily generated using plasmids available for the research community and can serve as a valuable tool for the detection, purification, and even subsequent elimination of HIV-1-resistant CD4 cells or CAR cells engineered to fight HIV-1 infection. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the primary causes of blindness worldwide. Canal opening surgery, a type of minimally invasive glaucoma surgery (MIGS) applied in cases of mild to moderate glaucoma, has gained increasing popularity in recent years due to its efficacy in reducing the intraocular pressure, its safety profile, the simplicity of its technique, and the reduced likelihood of compromised vision. Nevertheless, the existing body of histopathological studies remains insufficient for a comprehensive understanding of post-surgical wound healing. Consequently, debates persist among researchers regarding the mechanism through which Schlemm's canal opening surgery reduces the intraocular pressure, as well as the surgical techniques that may impact the outcomes and the factors influencing surgical success. As the history of MIGS is relatively short and lacks sufficient systemic reviews or meta-analyses evaluating the influence of individual factors, this review was conducted to illuminate the disparities in researchers' opinions at the current stage of research. [ABSTRACT FROM AUTHOR]

Precision agriculture has revolutionized crop management and agricultural production, with LiDAR technology attracting significant interest among various technological advancements. This extensive review examines the various applications of LiDAR in precision agriculture, with a particular emphasis on its function in crop cultivation and harvests. The introduction provides an overview of precision agriculture, highlighting the need for effective agricultural management and the growing significance of LiDAR technology. The prospective advantages of LiDAR for increasing productivity, optimizing resource utilization, managing crop diseases and pesticides, and reducing environmental impact are discussed. The introduction comprehensively covers LiDAR technology in precision agriculture, detailing airborne, terrestrial, and mobile systems along with their specialized applications in the field. After that, the paper reviews the several uses of LiDAR in agricultural cultivation, including crop growth and yield estimate, disease detection, weed control, and plant health evaluation. The use of LiDAR for soil analysis and management, including soil mapping and categorization and the measurement of moisture content and nutrient levels, is reviewed. Additionally, the article examines how LiDAR is used for harvesting crops, including its use in autonomous harvesting systems, post-harvest quality evaluation, and the prediction of crop maturity and yield. Future perspectives, emergent trends, and innovative developments in LiDAR technology for precision agriculture are discussed, along with the critical challenges and research gaps that must be filled. The review concludes by emphasizing potential solutions and future directions for maximizing LiDAR's potential in precision agriculture. This in-depth review of the uses of LiDAR gives helpful insights for academics, practitioners, and stakeholders interested in using this technology for effective and environmentally friendly crop management, which will eventually contribute to the development of precision agricultural methods. [ABSTRACT FROM AUTHOR]

The unique characteristics of an anti‐ambipolar switch (AAS) device exhibit Λ‐shaped transfer responses (namely delta conductance) and present unique opportunities to overcome the limit of silicon‐based, complementary metal‐oxide‐semiconductor (CMOS) logic circuits. It is crucial because a device that only turns on under a certain bias range can be utilized to simplify the logic circuit and reduce the device count and circuit area required to perform logic functions. In this study, a physically scalable AAS device is investigated using ZnO and dinaphtho[2,3‐b:2′,3′‐f]thieno[3,2‐b]thiophene as heterojunction structures to reduce the operating voltage and enhance the peak current and peak‐to‐valley ratio of the AAS device. Moreover, novel logic circuits for AND, OR, XOR, DEMUX, and half‐adder functions are demonstrated using AAS devices. AAS device‐based logic circuits exhibit power‐efficiency characteristics (≈49 times lower than that of the 90‐nm silicon‐based CMOS inverter) and reduce the transistor count and the circuit area by ≈67% and ≈70%, respectively. These results indicate that the use of AAS device‐based logic circuits can be a promising approach to overcome the physical scaling limit of current CMOS technology. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim of this study is to develop a cubosome nanoformulation for the optimized delivery of nimesulide, with a focus on improving its efficacy and reducing adverse effects. The ultimate goal is to advance the pharmaceutical application of nimesulide by achieving sustained release kinetics. Method: A systematic approach was employed to develop nine cubosomal formulations using a top-down strategy with the primary focus on optimizing the lipid (glyceryl monooleate - GMO: X1) and surfactant (Pluronic F-127 - PF-127: X2) concentrations. The selection of these variables was based on a 32-factorial design. The impact of varying concentrations of GMO and PF-127 on critical parameters such as particle size distribution and entrapment efficiency were thoroughly investigated. Results: The optimized formulation demonstrated favorable characteristics, including a particle size ranging from 153.5 ± 4.99 to 199.6 ± 10.23 nm, and EE between 70.5 ± 1.85 to 88 ± 2.17%. Zeta potential values ranged from − 35.6 to -40.5 mV, while PDI values fell within the range of 0.32 to 0.51. In vitro investigations revealed a meticulously sustained drug release profile with regulated kinetics observed over a 24 h period. Rheological studies provided insights into the viscoelastic behaviour and structural integrity of the cubosomal gel formulation. Ex vivo absorption studies conducted on goat skin demonstrated superior drug absorption and sustained release patterns compared to a commercially available gel. Conclusions: The study concludes that the application of nimesulide-loaded cubosomal gel has the potential to enhance drug absorption and facilitate sustained release. This nanoformulation presents a promising strategy for improving the topical delivery of nimesulide while minimizing adverse effects. [ABSTRACT FROM AUTHOR]

In 2010, G.-N. Han obtained the generating function for the number of size t hooks among integer partitions. Here we obtain these generating functions for self-conjugate partitions, which are particularly elegant for even t. If n_t(\lambda) is the number of size t hooks in a partition \lambda and \mathcal {SC} denotes the set of self-conjugate partitions, then for even t we have \begin{equation*} \sum _{\lambda \in \mathcal {SC}} x^{n_t(\lambda)} q^{\vert \lambda \vert } = (-q;q^2)_{\infty } \cdot ((1-x^2)q^{2t};q^{2t})_{\infty }^{\frac {t}{2}}. \end{equation*} As a consequence, if a_t^{\star }(n) is the number of such hooks among the self-conjugate partitions of n, then for even t we obtain the simple formula \begin{equation*} a_t^{\star }(n)=t\sum _{j\geq 1} q^{\star }(n-2tj), \end{equation*} where q^{\star }(m) is the number of partitions of m into distinct odd parts. As a corollary, we find that t\mid a_t^{\star }(n), which confirms a conjecture of Ballantine, Burson, Craig, Folsom and Wen. [ABSTRACT FROM AUTHOR]

Sexual dimorphism in temporomandibular disorders (TMDs) and their comorbidity with migraine are important phenomena observed in clinics. TMDs are the most prevalent orofacial pain conditions with jaw joint and masseter muscle dysfunction. Migraine is the predominant headache commonly associated with TMDs. Women much more often suffer from this orofacial pain than men. However, currently, there is no gender-specific therapy for such pain conditions. Understanding the pathophysiological mechanisms behind sex differences in TMDs as well as their comorbidity with migraines is essential for developing novel approaches for gender-specific treatment of TMDs and related orofacial pain comorbidity. In this review, we summarize recent research progress regarding sex differences in TMDs, focusing on the underlying mechanisms including craniofacial anatomy, hormonal regulation, and roles of opioids, transient receptor potential channels, and endocannabinoid systems. We also discuss the mechanisms of comorbid TMDs and migraine. The information covered in this review will provide mechanistic insights into sex differences in TMDs and their comorbidity with migraine, which could aid in developing effective treatment strategies for the overlapping orofacial pain condition. [ABSTRACT FROM AUTHOR]

This instrumental case study describes the steps taken to establish and implement a university–school partnership to improve rural science teachers' content knowledge and teaching practices and students' achievement in elementary science and high school biology courses. Our research questions explored the impact of professional development and place-based learning on student outcomes, with the study's methodology involving needs assessments, teacher training, and continuous support through modeling and coaching. The findings include gains in achievement and substantial gains in science education. The findings have implications for the design, implementation, and evaluation of university–school partnerships designed to build teachers' capacity to deliver high-quality science education and improve student success in rural school districts. [ABSTRACT FROM AUTHOR]

The National Water Model (NWM) provides critical analyses and projections of streamflow that support water management decisions. However, the NWM performs poorly in lower-elevation rivers of the western United States (US). The accuracy of the NWM depends on the fidelity of the model inputs and the representation and calibration of model processes and water sources. To evaluate the NWM performance in the western US, we compared observations of river water isotope ratios (18 O / 16 O and 2 H / 1 H expressed in δ notation) to NWM-flux-estimated (model) river reach isotope ratios. The modeled estimates were calculated from long-term (2000–2019) mean summer (June, July, and August) NWM hydrologic fluxes and gridded isotope ratios using a mass balance approach. The observational dataset comprised 4503 in-stream water isotope observations in 877 reaches across 5 basins. A simple regression between observed and modeled isotope ratios explained 57.9 % (δ18 O) and 67.1 % (δ2 H) of variance, although observations were 0.5 ‰ (δ18 O) and 4.8 ‰ (δ2 H) higher, on average, than mass balance estimates. The unexplained variance suggest that the NWM does not include all relevant water fluxes to rivers. To infer possible missing water fluxes, we evaluated patterns in observation–model differences using δ18Odiff (δ18Oobs-δ18Omod) and ddiff (δ2Hdiff-8⋅δ18Odiff). We detected evidence of evaporation in observations but not model estimates (negative ddiff and positive δ18Odiff) at lower-elevation, higher-stream-order, arid sites. The catchment actual-evaporation-to-precipitation ratio, the fraction of streamflow estimated to be derived from agricultural irrigation, and whether a site was reservoir-affected were all significant predictors of ddiff in a linear mixed-effects model, with up to 15.2 % of variance explained by fixed effects. This finding is supported by seasonal patterns, groundwater levels, and isotope ratios, and it suggests the importance of including irrigation return flows to rivers, especially in lower-elevation, higher-stream-order, arid rivers of the western US. [ABSTRACT FROM AUTHOR]

Phenotypic plasticity, the ability of a single genotype to produce different phenotypes under different environmental conditions, plays a profound role in several areas of evolutionary biology. One important role is as an adaptation to a variable environment. While plasticity is extremely well documented in response to many environmental factors, there is controversy over how much of that plasticity is adaptive. Evidence is also mixed over how often conspecific populations display qualitative differences in the nature of plasticity. We present data on the reaction norms of growth and maturation to variation in temperature and salinity in male and female sailfin mollies (Poecilia latipinna) from three locally adjacent populations from South Carolina (SC). We compare these reaction norms to those previously reported in locally adjacent populations from north Florida (NF). In general, patterns of plasticity in fish from SC were similar to those in fish from NF. The magnitude of plasticity differed; fish from SC displayed less plasticity than fish from NF. This was because SC fish grew faster and matured earlier at the lower temperatures and salinities compared to NF fish. This is a countergradient pattern of variation, in which SC fish grew faster and matured earlier in conditions that would otherwise slow growth and delay maturity. Among fish from both regions, males were much less plastic than females, especially for length at maturity. While there was no detectable heterogeneity among populations from NF, males from one of the SC populations, which is furthest from the other two, displayed a qualitatively different response in age at maturity to temperature variation than did males from the other two SC populations. The pattern of population variation in plasticity within and among regions suggests that gene flow, which diminishes with distance in sailfin mollies, plays a critical role in constraining divergence in norms of reaction. [ABSTRACT FROM AUTHOR]

High-mobility-group (HMG) proteins are small and relatively abundant chromatin-associated proteins, which act as architectural factors. In plants, two groups of chromosomal HMG proteins have been identified, namely the HMGA family, typically containing four A/T-hook DNA-binding motifs, and the HMGB family, containing a single HMG-box DNA-binding domain. The HMGA proteins are structurally flexible and bind A/T-rich DNA stretches. By orchestrating multiple protein-protein and protein-DNA interactions, they assist the formation of higher-order transcription factor complexes, regulating gene expression. The HMGB proteins bind DNA non-sequence-specifically, but specifically recognise DNA structures. Due to their remarkable DNA bending activity, they can enhance the structural flexibility of DNA, facilitating the assembly of nucleoprotein structures that control various DNA-dependent processes such as transcription and recombination. [ABSTRACT FROM AUTHOR]

white-mottled (Wm4) position-effect variegation (PEV) arises by translocation of the white gene near the pericentric AT-rich 1.688 g/cm3 satellite III (SATIII) repeats of the X chromosome of Drosophila. The natural and artificial A&Bull;T-hook proteins D1 and MATH2O modify wm4 PEV in opposite ways. D1 binds SATIII repeats and enhances PEV, presumably via a recruitment of protein partners, whereas MATH2O suppresses it. We show that D1 and MATH2O compete for binding to identical sites of SATIII repeats in vitro and that conditional MATH2O expression results in a displacement of D1 from pericentric heterochromatin in vivo. In the presence of intermediate levels of MATH2O, we show that this displacement becomes selective for SATIII repeats. These results strongly suggest that the suppression of wm4 PEV by MATH2O is due to a displacement of D1 from its preferred binding sites and provide additional support for a direct role of D1 in the assembly of AT-rich heterochromatin. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 2 (HIV-2) has already spread to different regions worldwide, and currently about 1 to 2 million people have been infected, calling for new antiviral agents that are effective on both HIV-1 and HIV-2 isolates. T20 (enfuvirtide), a 36-mer peptide derived from the C-terminal heptad repeat region (CHR) of gp41, is the only clinically approved HIV-1 fusion inhibitor, but it easily induces drug resistance and is not active on HIV-2. In this study, we first demonstrated that the M-T hook structure was also vital to enhancing the binding stability and inhibitory activity of diverse CHR-based peptide inhibitors. We then designed a novel short peptide (23-mer), termed 2P23, by introducing the M-T hook structure, HIV-2 sequences, and salt bridge-forming residues. Promisingly, 2P23 was a highly stable helical peptide with high binding to the surrogate targets derived from HIV-1, HIV-2, and simian immunodeficiency virus (SIV). Consistent with this, 2P23 exhibited potent activity in inhibiting diverse subtypes of HIV-1 isolates, T20-resistant HIV-1 mutants, and a panel of primary HIV-2 isolates, HIV-2 mutants, and SIV isolates. Therefore, we conclude that 2P23 has high potential to be further developed for clinical use, and it is also an ideal tool for exploring the mechanisms of HIV-1/2-and SIV-mediated membrane fusion. [ABSTRACT FROM AUTHOR]

Entry of HIV-1 into target cells is mediated by its envelope (Env) glycoprotein composed of the receptor binding subunit gp120 and the fusion protein gp41. Refolding of the gp41 N- and C-terminal heptad repeats (NHR and CHR) into a six-helix bundle (6-HB) conformation drives the viral and cellular membranes in close apposition and generates huge amounts of energy to overcome the kinetic barrier leading to membrane fusion. In this study, we focused on characterizing the structural and functional properties of a single Asn-145 residue, which locates at the middle CHR site of gp41 and is extremely conserved among all the HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates. By mutational analysis, we found that Asn-145 plays critical roles for Env-mediated cell-cell fusion and HIV-1 entry. As determined by circular dichroism (CD) spectroscopy and isothermal titration calorimetry (ITC), the substitution of Asn-145 with alanine (N145A) severely impaired the interactions between the NHR and CHR helices. Asn-145 was also verified to be important for the antiviral activity of CHR-derived peptide fusion inhibitors and served as a turn-point for the inhibitory potency. Intriguingly, Asn-145 could regulate the functionality of the M-T hook structure at the N-terminus of the inhibitors and displayed comparable activities with the C-terminal IDL anchor. Crystallographic studies further demonstrated the importance of Asn-145-mediated interhelical and intrahelical interactions in the 6-HB structure. Combined, the present results have provided valuable information for the structure-function relationship of HIV-1 gp41 and the structure-activity relationship of gp41-dependent fusion inhibitors. [ABSTRACT FROM AUTHOR]

Population and species persistence in a rapidly warming world will be determined by an organism's ability to acclimate to warmer conditions, especially across generations. There is potential for transgenerational acclimation but the importance of ontogenetic timing in the transmission of environmentally induced parental effects remains mostly unknown. We aimed to disentangle the effects of two critical ontogenetic stages (juvenile development and reproduction) to the new-generation acclimation potential, by exposing the spiny chromis damselfish Acanthochromis polyacanthus to simulated ocean warming across two generations. By using hepatic transcriptomics, we discovered that the post-hatching developmental environment of the offspring themselves had little effect on their acclimation potential at 2.5 months of life. Instead, the developmental experience of parents increased regulatory RNA production and protein synthesis, which could improve the offspring's response to warming. Conversely, parental reproduction and offspring embryogenesis in warmer water elicited stress response mechanisms in the offspring, with suppression of translation and mitochondrial respiration. Mismatches between parental developmental and reproductive temperatures deeply affected offspring gene expression profiles, and detrimental effects were evident when warming occurred both during parents' development and reproduction. This study reveals that the previous generation's developmental temperature contributes substantially to thermal acclimation potential during early life; however, exposure at reproduction as well as prolonged heat stress will likely have adverse effects on the species' persistence. [ABSTRACT FROM AUTHOR]

In this paper we show how the Functional Separation of Variables (FSoV) method can be applied to the problem of computing overlaps with integrable boundary states in integrable systems. We demonstrate our general method on the example of a particular boundary state, a singlet of the symmetry group, in an su 3 rational spin chain in an alternating fundamental-anti-fundamental representation. The FSoV formalism allows us to compute in determinant form not only the overlaps of the boundary state with the eigenstates of the transfer matrix, but in fact with any factorisable state. This includes off-shell Bethe states, whose overlaps with the boundary state have been out of reach with other methods. Furthermore, we also found determinant representations for insertions of so-called Principal Operators (forming a complete algebra of all observables) between the boundary and the factorisable state as well as certain types of multiple insertions of Principal Operators. Concise formulas for the matrix elements of the boundary state in the SoV basis and su N generalisations are presented. Finally, we managed to construct a complete basis of integrable boundary states by repeated action of conserved charges on the singlet state. As a result, we are also able to compute the overlaps of all of these states with integral of motion eigenstates. [ABSTRACT FROM AUTHOR]