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The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, β-galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non-image-forming visual functions.

We apply a global three-dimensional Goddard Earth Observing System (GEOS) chemical transport model (GEOS-Chem) driven by the NASA/GEOS-4 assimilated meteorological fields to quantify the impacts of the East Asian summer monsoon (EASM) on interannual variations of June-July-August (JJA) surface-layer O3 concentrations over China. With anthropogenic emissions fixed at year 2005 levels, the model simulation for years 1986–2006 shows that the changes in meteorological parameters alone lead to interannual variations in JJA surface-layer O3 concentrations by 2–5% over central eastern China, 1–3% in northwestern China, and 5–10% over the Tibetan Plateau as well as the border and coastal areas of southern China, as the interannual variations are relative to the average O3 concentrations over the 21 yr period. Over the years 1986–2006, the O3 concentration averaged over all of China is found to correlate positively with the EASM index with a large correlation coefficient of +0.75, indicating that JJA O3 concentrations are lower (or higher) in weaker (or stronger) EASM years. Relative to JJA surface-layer O3 concentrations in the strongest EASM years (1990, 1994, 1997, 2002, and 2006), O3 levels in the weakest EASM years (1988, 1989, 1996, 1998, and 2003) are lower over almost all of China with a national mean lower O3 concentration by 2.0 ppbv (parts per billion by volume; or 4%). Regionally, the largest percentage differences in O3 concentration between the weakest and strongest EASM years are found to exceed 6% in northeastern China, southwestern China, and over the Tibetan Plateau. Sensitivity studies show that the difference in transboundary transport of O3 is the most dominant factor that leads to lower-O3 concentrations in the weakest EASM years than in the strongest EASM years, which, together with the enhanced vertical convections in the weakest EASM years, explain about 80% of the differences in surface-layer O3 concentrations between the weakest and strongest EASM years. We also find that the impacts the EASM strength on JJA surface-layer O3 can be particularly strong (comparable in magnitude to the impacts on O3 by changes in anthropogenic emissions over years 1986–2006) for certain years. The largest increases in O3 by anthropogenic emissions are simulated over southeastern China, whereas the largest impacts of the EASM on O3 are found over central and western China.

A single-shot burst camera has been developed that can generate motion pictures without performing repetitive measurements. It has a frame rate of 4.4 trillion frames per second and a high pixel resolution of 450 × 450 pixels, making it a powerful tool for observing difficult-to-reproduce or non-repetitive events in real time. High-speed photography 1 , 2 , 3 is a powerful tool for studying fast dynamics in photochemistry 4 , 5 , spintronics 6 , 7 , phononics 8 , 9 , fluidics 10 , 11 and plasma physics 12 . Currently, the pump–probe method is the gold standard for time-resolved imaging 4 , 5 , 6 , 8 , 12 , 13 , 14 , 15 , 16 , 17 , but it requires repetitive measurements for image construction and therefore falls short in probing non-repetitive or difficult-to-reproduce events. Here, we present a motion-picture camera that performs single-shot burst image acquisition without the need for repetitive measurements, yet with equally short frame intervals (4.4 trillion frames per second) and high pixel resolution (450 × 450 pixels). The principle of this method—‘motion picture femtophotography’—is all-optical mapping of the target's time-varying spatial profile onto a burst stream of sequentially timed photographs with spatial and temporal dispersion. To show the camera's broad utility we use it to capture plasma dynamics and lattice vibrational waves, both of which were previously difficult to observe with conventional methods in a single shot and in real time.

We used the nested grid version of the global three-dimensional Goddard Earth Observing System chemical transport model (GEOS-Chem) to examine the interannual variations (IAVs) of aerosols over heavily polluted regions in China for years 2004–2012. The role of variations in meteorological parameters was quantified by a simulation with fixed anthropogenic emissions at year 2006 levels and changes in meteorological parameters over 2004–2012. Simulated PM2.5 (particles with a diameter of 2.5 μm or less) aerosol concentrations exhibited large IAVs in North China (NC; 32–42° N, 110–120° E), with regionally averaged absolute percent departure from the mean (APDM) values of 17, 14, 14, and 11% in December-January-February (DJF), March-April-May (MAM), June-July-August (JJA), and September-October-November (SON), respectively. Over South China (SC; 22–32° N, 110–120° E), the IAVs in PM2.5 were found to be the largest in JJA, with the regional mean APDM values of 14% in JJA and of about 9% in other seasons. The concentrations of PM2.5 over the Sichuan Basin (SCB; 27–33° N, 102–110° E) were simulated to have the smallest IAVs among the polluted regions examined in this work, with APDM values of 8–9% in all seasons. All aerosol species (sulfate, nitrate, ammonium, black carbon, and organic carbon) were simulated to have the largest IAVs over NC in DJF, corresponding to the large variations in meteorological parameters over NC in this season. Process analyses were performed to identify the key meteorological parameters that determined the IAVs of different aerosol species in different regions. While the variations in temperature and specific humidity, which influenced the gas-phase formation of sulfate, jointly determined the IAVs of sulfate over NC in both DJF and JJA, wind (or convergence of wind) in DJF and precipitation in JJA were the dominant meteorological factors to influence IAVs of sulfate over SC and the SCB. The IAVs in temperature and specific humidity influenced gas-to-aerosol partitioning, which were the major factors that led to the IAVs of nitrate aerosol in China. The IAVs in wind and precipitation were found to drive the IAVs of organic carbon aerosol. We also compared the IAVs of aerosols simulated with variations in meteorological parameters alone with those simulated with variations in anthropogenic emissions alone; the variations in meteorological fields were found to dominate the IAVs of aerosols in northern and southern China over 2004–2012. Considering that the IAVs in meteorological fields are mainly associated with natural variability in the climate system, the IAVs in aerosol concentrations driven by meteorological parameters have important implications for the effectiveness of short-term air quality control strategies in China.

Takayasu's arteritis (TAK) is a chronic, large-vessel vasculitis that mostly affects young Asian women[1-4]. Vascular inflammation in TAK primarily invades the aorta and its major branches and often leads to arterial stenosis and aneurysms. At present, there is no relevant research report on how to identify the vascular lesions of organs in the early stage and the relationship between the affected vessels. To investigate the correlation of arterial involvement sites in Takayasu arteritis. We retrospectively investigated data of 144 TAK patients. The clinical and image data of the patients were analyzed. We performed cluster analysis according to the affected artery. cluster analysis revealed five clusters of patients. In cluster one was named “abdominal aortic type”. It was characterized by the involvement of arteries in the abdominal aorta, renal artery, coeliac trunk, superior mesenteric artery. In cluster two was named “cardio-cerebral arteries type”. It was characterized by the involvement of arteries in the intracranial artery, coronary artery. In cluster three was named “thoracic aorta type”. It was characterized by the involvement of arteries in the thoracic aorta and pulmonary artery was observed. In cluster four was named “vertebral artery type”. It was characterized by the involvement of arteries in the left vertebral artery, right vertebral artery. In cluster five was named “carotid artery type”. It was characterized by the involvement of arteries in the right common carotid artery, left common carotid artery, right subclavian artery, left subclavian artery, innominate artery. Cluster analysis of the involved sites of Takayasu arteritis could be divided into 5 categories. It is abdominal aortic type, cardio-cerebral arteries type, thoracic aorta type, vertebral artery type and carotid artery type. [1]Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33(8):1129–34. [2]de Souza AW, de Carvalho JF. Diagnostic and classification criteria of Takayasu arteritis. J Autoimmun. 2014;48-49:79–83. [3]Park SJ, Kim HJ, Park H, Hann HJ, Kim KH, Han S, et al. Incidence, prevalence, mortality and causes of death in Takayasu Arteritis in Korea – A nationwide, population-based study. Int J Cardiol. 2017;235:100–4. [4]Stamatis P. Giant cell arteritis versus Takayasu arteritis: an update. Mediterr J Rheumatol. 2020;31(2):174–82. NIL. None Declared.

Developing clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important in the era of personalized medicine. Liver-directed gene therapies present a unique challenge due to the complexity of the human liver. In this work, we describe the application of whole human liver explants in an ex situ normothermic perfusion system to evaluate a set of fourteen natural and bioengineered adeno-associated viral (AAV) vectors directly in human liver, in the presence and absence of neutralizing human sera. Under non-neutralizing conditions, the recently developed AAV variants, AAV-SYD12 and AAV-LK03, emerged as the most functional variants in terms of cellular uptake and transgene expression. However, when assessed in the presence of human plasma containing anti-AAV neutralizing antibodies (NAbs), vectors of human origin, specifically those derived from AAV2/AAV3b, were extensively neutralized, whereas AAV8- derived variants performed efficiently. This study demonstrates the potential of using normothermic liver perfusion as a model for early-stage testing of liver-focused gene therapies. The results offer preliminary insights that could help inform the development of more effective translational strategies. Developing clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important. This study introduces human liver ex situ normothermic perfusion as a model to evaluate gene therapy vectors, paving the way for advanced liver disease treatment.

Background: Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials. Methods: At 14 breast centres across China during 2008–2010, 13 339 high-risk women aged 30–65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrolment and 1-year follow-up. Results: A total of 12 519 and 8692 women underwent the initial and second screenings, respectively. Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group ( P =0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P =0.04) with a better diagnostic accuracy (0.999 vs 0.766, P =0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P =0.51) and positive predictive value (72.7 vs 70.0%; P =0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively. Conclusions: Ultrasound is superior to mammography for breast cancer screening in high-risk Chinese women.

Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. Sixty-nine middle-aged (501–64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a highprotein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.

Purpose The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair (RIHR) from multi-institutional experience in Taiwan. Methods Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery. Results A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%, p  = 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3, p  < 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%, p  < 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%, p  = 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%, p  = 0.016) (Opioid prescription: RIHR 3.34 mg vs LIHR 10.82 mg, p  = 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27 min vs LIHR 95.30 min, p < 0.001). Conclusions This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.

Background:Takayasu arteritis（TA）can involve coronary artery lesions. Previous studies have shown that the incidence of TA complicated with coronary artery lesion is 3.6%-53.2%[1,2],The incidence of acute myocardial infarction is 5.9%-12.06%[3, 4]. Tocilizumab treatment could significantly improved TA with coronary artery lesion[5]. But,the pathogenesis of takayasu arteritis complicated with coronary artery lesion is very complex, and the influencing factors are still unclear, and there is no optimal treatment strategy for these patients.If TA with concurrent coronary artery involvement is not promptly identified, it may lead to major adverse cardiac events (MACE).Objectives:This study aimed to investigate the influencing factors of pharmacologic improvement of TA with coronary artery lesion, as well as to conduct a prognosis analysis.Methods:This retrospective study enrolled 188 TA patients. All patients were divided into two groups according to the absence or presence of coronary artery lesion. This study compared baseline general information, traditional risk factors, disease activity, treatment modalities, changes in imaging before and after treatment and recorded MACE between the two groups. Logistic regression and cox regression were employed to determine the risk factors for coronary artery lesions in TA patients and factors influencing prognosis.Results:The incidence of coronary artery involvement in TA is 48.40%.Logistic regression analysis showed that hypertension (p=0.002, OR 2.298,95%CI:1.499-5.720) and hyperlipidemia(p<0.001, OR 13.706,95%CI:3.796-49.486).However, type I in TA patients was less likely to develop coronary artery disease (p=0.046, OR0.278 95% CI:0.079-0.980).We conducted follow-up with 44 TAK patients who underwent pre- and post-contrast coronary CTA, and compared and analyzed the occurrence of MACE.Cox regression analysis showed coronary artery lesions in TA patients of Type IIb tend to improve more easily (p=0.005, HR 4.559,95%CI:1.563-13.293)and tocilizumab therapy can significantly improve coronary artery lesions in TA patients.(p=0.006,HR 4.284,95%CI:1.509-12.158). In terms of improvement in coronary artery lesions, the most significant changes were observed in the opening of the left main trunk, proximal narrowing of the anterior descending branch, and improvements in concentric lesions.The incidence of MACE after immunotherapy decreased from 33.3% within six months to 2.33%. The occurrence time of MACE extended from 3.50 (1.00, 6.75) months before treatment to 15.00 (10.00, 49.00) (p=0.008)months after treatment.Conclusion:Hypertension and hyperlipidemia are risk factors for the development of coronary artery lesions in TA. Tocilizumab significantly improves coronary artery lesions in TA patients, with coronary artery lesions of Numano Type IIb more easily amenable to improvement. Regular immunotherapy reduces the occurrence rate of MACE and significantly prolongs the time to MACE in TA patients with concurrent coronary artery lesions.REFERENCES:[1] Li J, Sun F, Chen Z, Yang Y, Zhao J, Li M, Tian X, Zeng X: The clinical characteristics of Chinese Takayasu’s arteritis patients: a retrospective study of 411 patients over 24 years. Arthritis Res Ther 2017, 19(1):107.[2] Kang EJ, Kim SM, Choe YH, Lee GY, Lee KN, Kim DK: Takayasu arteritis: assessment of coronary arterial abnormalities with 128-section dual-source CT angiography of the coronary arteries and aorta. Radiology 2014, 270(1):74-81.[3] Yuan SM, Lin HZ: Coronary artery involvements in Takayasu arteritis: systematic review of reports. Gen Thorac Cardiovasc Surg 2020, 68(9):883-904.[4] Huo J, Wang B, Yu L, Gao D, Cheng R, Wang J, Zhou X, Tian T, Gao L: Clinical characteristics and outcomes in patients with Takayasu arteritis coexisting with myocardial ischemia and neurological symptoms: A multicenter, long-term, follow-up study. Front Cardiovasc Med 2022, 9:948124.[5] Pan L, Du J, Liu J, Liao H, Liu X, Guo X, Liang J, Han H, Yang L, Zhou Y: Tocilizumab treatment effectively improves coronary artery involvement in patients with Takayasu arteritis. Clin Rheumatol 2020, 39(8):2369-2378.Figure 1.Acknowledgements:NIL.Disclosure of Interests:None declared.