Contribution of anthropogenic aerosols to persistent La Niña-like conditions in the early 21st century.

The discrepancy between the observed lack of surface warming in the eastern equatorial Pacific and climate model projections of an El Niño-like warming pattern confronts the climate research community. While anthropogenic aerosols have been suggested as a cause, the prolonged cooling trend over the equatorial Pacific appears in conflict with Northern Hemisphere aerosol emission reduction since the 1980s. Here, using CESM, we show that the superposition of fast and slow responses to aerosol emission change-an increase followed by a decrease-can sustain the La Niña-like condition for a longer time than expected. The rapid adjustment of Hadley Cell to aerosol reduction triggers joint feedback between low clouds, wind, evaporation, and sea surface temperature in the Southeast Pacific, leading to a wedge-shaped cooling that extends to the central equatorial Pacific. Meanwhile, the northern subtropical cell gradually intensifies, resulting in equatorial subsurface cooling that lasts for decades.

Distinct roles of the dystrophin-glycoprotein complex: α-dystrobrevin and α-syntrophin in the maintenance of the postsynaptic apparatus of the neuromuscular synapse.

α-syntrophin (α-syn) and α-dystrobrevin (α-dbn), two components of the dystrophin-glycoprotein complex, are essential for the maturation and maintenance of the neuromuscular junction (NMJ) and mice deficient in either α-syn or α-dbn exhibit similar synaptic defects. However, the functional link between these two proteins and whether they exert distinct or redundant functions in the postsynaptic organization of the NMJ remain largely unknown. We generated and analyzed the synaptic phenotype of double heterozygote (α-dbn+/-, α-syn+/-), and double homozygote knockout (α-dbn-/-; α-syn-/-) mice and examined the ability of individual molecules to restore their defects in the synaptic phenotype. We showed that in double heterozygote mice, NMJs have normal synaptic phenotypes and no signs of muscular dystrophy. However, in double knockout mice (α-dbn-/-; α-syn-/-), the synaptic phenotype (the density, the turnover and the distribution of AChRs within synaptic branches) is more severely impaired than in single α-dbn-/- or α-syn-/- mutants. Furthermore, double mutant and single α-dbn-/- mutant mice showed more severe exercise-induced fatigue and more significant reductions in grip strength than single α-syn-/- mutant and wild-type. Finally, we showed that the overexpression of the transgene α-syn-GFP in muscles of double mutant restores primarily the abnormal extensions of membrane containing AChRs that extend beyond synaptic gutters and lack synaptic folds, whereas the overexpression of α-dbn essentially restores the abnormal dispersion of patchy AChR aggregates in the crests of synaptic folds. Altogether, these data suggest that α-syn and α-dbn act in parallel pathways and exert distinct functions on the postsynaptic structural organization of NMJs.

The safety and response of CT guided percutaneous cryoablation for lung nodules by 17-gauge needles.

BACKGROUND: The safety and efficacy of 17-gauge needles used in CT-guided percutaneous cryoablation for lung nodules were explored in this study. The purpose of the study was to compare the findings with earlier research and multi-center clinical trials that used various needle sizes. METHODS: Between 2016 and 2020, a retrospective study was conducted with approval from the institutional review board. A total of 41 patients were enrolled, and 71 lung nodules were treated in 63 cryoablation procedures using local anesthesia. Complication rates were recorded, and overall survival rates as well as tumor progression-free rates were calculated using the Kaplan-Meier method. RESULTS: Self-limited hemoptysis was caused by 12.9% of the procedures, and drainage was required for pneumothoraces resulting from 11.3% of them. The overall survival rates at one, two, three, and four years were 97%, 94%, 82%, and 67%, respectively. The tumor progression-free rates at one, two, three, and four years were 86.2%, 77%, 74%, and 65%, respectively. CONCLUSION: Cryoablation for lung nodules using 17-Gauge needles can achieve similar rates of survival and tumor control rates, similar or even lower complication rates as compared with other studies and multi-center trials using mixed sized needles.

Phosphorylation of α-dystrobrevin is essential for αkap accumulation and acetylcholine receptor stability.

The maintenance of a high density of the acetylcholine receptor (AChR) is the hallmark of the neuromuscular junction. Muscle-specific anchoring protein (αkap) encoded within the calcium/calmodulin-dependent protein kinase IIα (CAMK2A) gene is essential for the maintenance of AChR clusters both in vivo and in cultured muscle cells. The underlying mechanism by which αkap is maintained and regulated remains unknown. Here, using human cell lines, fluorescence microscopy, and pulldown and immunoblotting assays, we show that α-dystrobrevin (α-dbn), an intracellular component of the dystrophin glycoprotein complex, directly and robustly promotes the stability of αkap in a concentration-dependent manner. Mechanistically, we found that the phosphorylatable tyrosine residues of α-dbn are essential for the stability of α-dbn itself and its interaction with αkap, with substitution of three tyrosine residues in the α-dbn C terminus with phenylalanine compromising the αkap-α-dbn interaction and significantly reducing both αkap and α-dbn accumulation. Moreover, the αkap-α-dbn interaction was critical for αkap accumulation and stability. We also found that the absence of either αkap or α-dbn markedly reduces AChRα accumulation and that overexpression of α-dbn or αkap in cultured muscle cells promotes the formation of large agrin-induced AChR clusters. Collectively, these results indicate that the stability of αkap and α-dbn complex plays an important role in the maintenance of high-level expression of AChRs.

Travel for mindfulness through Zen retreat experience: A case study at Donghua Zen Temple.

This study seeks to contribute knowledge of the Zen retreat experience unique to Buddhist tourism. The research setting is the Zen retreats found at the Donghua Zen Temple in China. This study examined feedback obtained from 520 tourists who stayed at Zen retreats. Zen retreat organizer insights were obtained through online discussions. This study identified four motivations for, and three outcomes of, staying at Zen retreats. Within the Zen retreat experience, this study clarified four themes in knowledge growth (mingxin), three themes in spiritual growth (jianxing), and two mechanisms to foster knowledge and spiritual growth. This study further proposed a figure demonstrating Zen practitioners' lifelong journey, and a figure categorizing tourists in Buddhist tourism into Zen tourism, Zen lifestyle, and Zen retreat by level of involvement.

Beyond the display: phase-only liquid crystal on Silicon devices and their applications in photonics [Invited].

Existing for almost four decades, liquid crystal on Silicon (LCOS) technology is rapidly growing into photonic applications. We review the basics of the technology, from the wafer to the driving solutions, the progress over the last decade and the future outlook. Furthermore we review the most exciting industrial and scientific applications of the LCOS technology.

Unusual synchronous double primary treatment-naïve lung adenocarcinoma harboring T790M and L858R mutations in early-stage lung cancer.

BACKGROUND: Concurrent mutations of synchronous multiple primary non-small cell lung cancer (SMPNSCLC) is rare, and only a few cases have been reported. Herein, we present a case of early-stage SMPNSCLC with T790M and L858R mutations. CASE PRESENTATION: A 68-year-old male patient presented to the Thoracic Surgery Department due to a tumor in the right lower lung. The tumor was detected more than 5 years previously during a health examination; however, the patient ignored the problem because the clinician at that time stated that the lesion was highly likely to be benign. Chest computed topography (CT) was ordered and the images showed a well-defined tumor in the right lower lung and a faint nodular lesion over the left lower lung field. A CT-guided biopsy results showed the presence of atypical cells and positive staining of TTF-1 and CK7. Surgical intervention was performed. The right- and left-sided tumors disclosed micropapillary predominant adenocarcinoma and acinar-predominant adenocarcinoma, respectively. Both tumors were positive for TTF-1 but negative for ALK and p40. Real-time PCR analysis showed that the right-sided tumor had an epidermal growth factor receptor (EGFR) mutation presenting as point mutation T790M in exon 20, while the left-sided tumor had a point mutation L858R in exon 21 of EGFR. CONCLUSIONS: Our patient's case suggests that tumors resembling a benign pattern with central calcification may be misdiagnosed. Thus, early screening for lung cancer is important, and intensive efforts to make a diagnosis through surgical resection or biopsies to allow for tailored optimal treatment may be preferential for the best patient outcomes.

AChRs Are Essential for the Targeting of Rapsyn to the Postsynaptic Membrane of NMJs in Living Mice.

UNLABELLED: Rapsyn, a 43 kDa scaffold protein, is required for the clustering of acetylcholine receptors (AChRs) at synaptic sites between mammalian motor neurons and muscle cells. However, the mechanism by which rapsyn is inserted and retained at postsynaptic sites at the neuromuscular junction (NMJ) in vivo remains largely unknown. We found that neither the N-terminal myristoylation nor the cysteine-rich RING H2 domain of rapsyn is required for its stable association with the postsynaptic membrane of NMJs. When N-myristoylation-defective rapsyn-EGFP mutant (G2A) and RING-H2 domain truncated rapsyn-EGFP were electroporated into sternomastoid muscles, a strong rapsyn fluorescent signal was observed selectively at synapses, similar to WT rapsyn-EGFP. The targeting of rapsyn-EGFP (WT and mutants) is independent of synaptic activity because they were inserted at denervated NMJs. However, when the coiled-coil domain (the AChR-binding domain of rapsyn) is deleted, rapsyn fails to associate with AChRs at NMJs of living mice. In cultured myoblasts (in which AChRs are absent), myristoylated WT rapsyn mostly localizes to lysosomes and is not associated with the plasma membrane. However, in the presence of AChR subunits, rapsyn molecules were targeted to the cell surface and formed aggregates with AChRs. The targeting of AChRs to the cell membrane, in contrast, does not require rapsyn because expressed AChRs are visible on the cell membranes of rapsyn-deficient myoblasts. These results provide evidence for an active role of AChRs in the targeting of rapsyn to the NMJ in vivo SIGNIFICANCE STATEMENT: Rapsyn is required for the clustering of acetylcholine receptors (AChRs) at postsynaptic sites. However, the mechanism by which rapsyn is targeted to synaptic sites at the vertebrate neuromuscular junction remains unclear. In this study, we showed that the coiled-coil domain of rapsyn is required for its targeting to the cell surface via its interaction with AChRs. In contrast, the targeting of AChRs to the cell membrane does not require rapsyn. These results indicate that AChRs play a critical role in the insertion and/or association of rapsyn with the plasma membrane of synaptic sites.

Failure of lysosome clustering and positioning in the juxtanuclear region in cells deficient in rapsyn.

Rapsyn, a scaffold protein, is required for the clustering of acetylcholine receptors (AChRs) at contacts between motor neurons and differentiating muscle cells. Rapsyn is also expressed in cells that do not express AChRs. However, its function in these cells remains unknown. Here, we show that rapsyn plays an AChR-independent role in organizing the distribution and mobility of lysosomes. In cells devoid of AChRs, rapsyn selectively induces the clustering of lysosomes at high density in the juxtanuclear region without affecting the distribution of other intracellular organelles. However, when the same cells overexpress AChRs, rapsyn is recruited away from lysosomes to colocalize with AChR clusters on the cell surface. In rapsyn-deficient (Rapsn(-/-)) myoblasts or cells overexpressing rapsyn mutants, lysosomes are scattered within the cell and highly dynamic. The increased mobility of lysosomes in Rapsn(-/-) cells is associated with a significant increase in lysosomal exocytosis, as evidenced by increased release of lysosomal enzymes and plasma membrane damage when cells were challenged with the bacterial pore-forming toxin streptolysin-O. These findings uncover a new link between rapsyn, lysosome positioning, exocytosis and plasma membrane integrity.

The knockdown of αkap alters the postsynaptic apparatus of neuromuscular junctions in living mice.

A muscle-specific nonkinase anchoring protein (αkap), encoded within the calcium/calmodulin kinase II (camk2) α gene, was recently found to control the stability of acetylcholine receptor (AChR) clusters on the surface of cultured myotubes. However, it remains unknown whether this protein has any effect on receptor stability and the maintenance of the structural integrity of neuromuscular synapses in vivo. By knocking down the endogenous expression of αkap in mouse sternomastoid muscles with shRNA, we found that the postsynaptic receptor density was dramatically reduced, the turnover rate of receptors at synaptic sites was significantly increased, and the insertion rates of both newly synthesized and recycled receptors into the postsynaptic membrane were depressed. Moreover, we found that αkap shRNA knockdown impaired synaptic structure as postsynaptic AChR clusters and their associated postsynaptic scaffold proteins within the neuromuscular junction were completely eliminated. These results provide new mechanistic insight into the role of αkap in regulating the stability of the postsynaptic apparatus of neuromuscular synapses.

Electrically adjustable location of a projected image in augmented reality via a liquid-crystal lens.

An augmented reality (AR) system involving the electrically tunable location of a projected image is implemented using a liquid-crystal (LC) lens. The projected image is either real or virtual. By effectively doubling the LC lens power following light reflection, the position of a projected virtual image can be made to vary from 42 to 360 cm, while the tunable range for a projected real image is from 27 to 52 cm on the opposite side. The optical principle of the AR system is introduced and could be further developed for other tunable focusing lenses, even those with a lower lens power. The benefits of this study could be extended to head-mounted display systems for vision correction or vision compensation. We believe that tunable focusing LC optical elements are promising developments in the thriving field of AR applications.

Electrically tunable microlens arrays based on polarization-independent optical phase of nano liquid crystal droplets dispersed in polymer matrix.

Electrically tunable focusing microlens arrays based on polarization independent optical phase of nano liquid crystal droplets dispersed in polymer matrix are demonstrated. Such an optical medium is optically isotropic which is so-called an optically isotropic liquid crystals (OILC). We not only discuss the optical theory of OILC, but also demonstrate polarization independent optical phase modulation based on the OILC. The experimental results and analytical discussion show that the optical phase of OILC microlens arrays results from mainly orientational birefringence which is much larger than the electric-field-induced birefringence (or Kerr effect). The response time of OILC microlens arrays is fast~5.3ms and the tunable focal length ranges from 3.4 mm to 3.8 mm. The potential applications are light field imaging systems, 3D integrating imaging systems and devices for augment reality.

An electrically tunable imaging system with separable focus and zoom functions using composite liquid crystal lenses.

We demonstrated an electrically tunable optical image system with separable focus function and zoom function based on three tunable focusing composite liquid crystal (LC) lenses. One LC lens in charge of the focus function helps to maintain the formed image at the same position and the other two LC lenses in charge of zoom function assist to continuously form an image at image sensor with tunable magnification of image size. The detail optical mechanism is investigated and the concept is demonstrated experimentally. The magnifications of the images can be switched continuously for the target in a range between 10 cm and 100 cm. The optical zoom ratio of this system maintains a constant~6.5:1 independent of the object distance. This study provides not only a guideline to design the image system with an electrically optical zoom, but also provide an experimental process to show how to operate the tunable focusing lenses in such an image system.

Association Between Osteoporosis and Adiposity Index Reveals Nonlinearity Among Postmenopausal Women and Linearity Among Men Aged over 50 Years.

PURPOSE: Previous research shows conflicting views on the relationship between obesity and osteoporosis, partly due to variations in obesity classification and the nonlinear nature of these relationships. This study investigated the association between adiposity indices and osteoporosis, diagnosed using dual-energy X-ray absorptiometry (DXA), employing nonlinear models and offering optimal thresholds to prevent further bone mineral density decline. METHODS: In 2019, a prospective study enrolled males over 50 years and postmenopausal women. Anthropometric measurements, blood biochemistry, and osteoporosis measured by DXA were collected. Associations between adiposity indices and osteoporosis were analyzed using a generalized additive model and segmented regression model. RESULTS: The study included 872 women and 1321 men. Indices such as abdominal volume index (AVI), visceral adiposity index (VAI), waist circumference (WC), hip circumference, body mass index (BMI), waist-to-hip ratio, and waist-to-height ratio (WHtR) were inversely associated with osteoporosis. In women, the relationship between the risk of osteoporosis and the adiposity indices was U-shaped, with thresholds of WC = 94 cm, AVI = 17.67 cm2, BMI = 25.74 kg/m2, VAI = 4.29, and WHtR = 0.61, considering changes in bone mineral density. Conversely, men exhibited a linear patterns for the inverse association. CONCLUSION: The impact of obesity and adiposity on osteoporosis varies significantly between women and men. In postmenopausal women, the relationship is nonlinear (U-shaped), with both very low and very high adiposity linked to higher osteoporosis risk. In men over 50, the relationship is linear, with higher adiposity associated with lower osteoporosis risk. The study suggests that maintaining specific levels of adiposity could help prevent osteoporosis in postmenopausal women.

Tumor Location Is an Independent Prognostic Factor in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer: A Multicenter Retrospective Study.

Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes.

Association between exposure to organophosphate flame retardants and epidermal growth factor receptor expression in lung cancer patients.

BACKGROUND: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. METHODS: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. RESULTS: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. CONCLUSIONS: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.

Community-Based Screening for Hepatitis B and C Infectivity Using Two Quantitative Antigens to Identify Endemic Townships.

Screening and linkage to care are essential to achieve viral hepatitis elimination before 2030. The accurate identification of endemic areas is important for controlling diseases with geographic aggregation. Viral activity drives prognosis of chronic hepatitis B and hepatitis C virus infection. This screening was conducted in Chiayi County from 2018-2019. All residents aged 30 years or older were invited to participate in quantitative HBsAg (qHBsAg) and HCV Ag screening. Among the 4010 participants (male:female = 1630:2380), the prevalence of qHBsAg and HCV Ag was 9.9% (396/4010) and 4.1% (163/4010), respectively. High-prevalence townships were identified, three for qHBsAg > 15% and two for HCV Ag > 10%. The age-specific prevalence of qHBsAg was distributed in an inverse U-shape with a peak (16.0%, 68/424) for subjects in their 40 s; for HCV, prevalence increased with age. Concentrations of qHBsAg < 200 IU/mL were found in 54% (214/396) of carriers. The rate of oral antiviral treatment for HCV was 75.5% (114/151), with subjects younger than 75 years tending to undergo treatment (85.6% vs. 57.4%, p < 0.001). QHBsAg and HCV Ag core antigens can reflect the concentration of the viral load, which serves as a feasible screening tool. Using quantitative antigen screening for hepatitis B and C in community-based screening, two hyperendemic townships were identified from an endemic county.

Factors associated with hyperhomocysteinemia in relatively healthy Taiwanese adults: A retrospective medical record study.

ABSTRACT: Elevated homocysteine levels have been proposed as a risk factor for cardiovascular disease. The aim of this study was to evaluate factors associated with hyperhomocysteinemia in relatively healthy Taiwanese adults.A retrospective cross-sectional study was conducted using data from the health examination database in a medical center located in southern Taiwan. Hyperhomocysteinemia was defined as a plasma homocysteinemia level >15 µmol/L. Factors associated with hyperhomocysteinemia were evaluated using univariate and multiple stepwise logistic regression analyses.A total of 817 adults with a mean age of 55.5 years were included in the present study, and of them, 67 (8.2%) had hyperhomocysteinemia. Results from multiple logistic regression analysis showed that male sex (Odd ratio [OR] = 12.28, 95% CI = 2.94-51.27, P  = .001), advanced age (OR = 1.37 per 10 years, 95% CI = 1.06-1.77, P = .017), triglycerides (OR = 1.02 per 10 mg/dL, 95% CI = 1.01-1.04, P = .010), and uric acid (OR = 1.27, 95% CI = 1.09-1.49, P = .004) were significantly and independently associated with hyperhomocysteinemia.In this retrospective medical record study, male sex, advanced age, higher plasma level of triglyceride, and uric acid were significantly associated with hyperhomocysteinemia in relatively healthy Taiwanese adults.

Augmented reality with image registration, vision correction and sunlight readability via liquid crystal devices.

Augmented reality (AR), which use computer-aided projected information to augment our sense, has important impact on human life, especially for the elder people. However, there are three major challenges regarding the optical system in the AR system, which are registration, vision correction, and readability under strong ambient light. Here, we solve three challenges simultaneously for the first time using two liquid crystal (LC) lenses and polarizer-free attenuator integrated in optical-see-through AR system. One of the LC lens is used to electrically adjust the position of the projected virtual image which is so-called registration. The other LC lens with larger aperture and polarization independent characteristic is in charge of vision correction, such as myopia and presbyopia. The linearity of lens powers of two LC lenses is also discussed. The readability of virtual images under strong ambient light is solved by electrically switchable transmittance of the LC attenuator originating from light scattering and light absorption. The concept demonstrated in this paper could be further extended to other electro-optical devices as long as the devices exhibit the capability of phase modulations and amplitude modulations.