The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors.

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

Efficient scavenging of reactive carbonyl species in chloroplasts is required for light acclimation and fitness of plants.

Reactive carbonyl species (RCS) derived from lipid peroxides can act as critical damage or signaling mediators downstream of reactive oxygen species by modifying target proteins. However, their biological effects and underlying mechanisms remain largely unknown in plants. Here, we have uncovered the mechanism by which the RCS 4-hydroxy-(E)-2-nonenal (HNE) participates in photosystem II (PSII) repair cycle of chloroplasts, a crucial process for maintaining PSII activity under high and changing light conditions. High Light Sensitive 1 (HLT1) is a potential NADPH-dependent reductase in chloroplasts. Deficiency of HLT1 had no impact on the growth of Arabidopsis plants under normal light conditions but increased sensitivity to high light, which resulted from a defective PSII repair cycle. In hlt1 plants, the accumulation of HNE-modified D1 subunit of PSII was observed, which did not affect D1 degradation but hampered the dimerization of repaired PSII monomers and reassembly of PSII supercomplexes on grana stacks. HLT1 is conserved in all photosynthetic organisms and has functions in overall growth and plant fitness in both Arabidopsis and rice under naturally challenging field conditions. Our work provides the mechanistic basis underlying RCS scavenging in light acclimation and suggests a potential strategy to improve plant productivity by manipulating RCS signaling in chloroplasts.

Adaptive Optics Tip-Tilt Correction Based on Smith Predictor and Filter-Optimized Linear Active Disturbance Rejection Control Method.

A tip-tilt mirror (TTM) control method is designed to enhance the control bandwidth and ensure the rejection performance of the adaptive optics (AO) tip-tilt correction system. Optimized with the Smith predictor and filter, linear active disturbance rejection (LADRC) is adopted to achieve the tip-tilt correction. An AO tip-tilt correction experimental platform was built to validate the method. Experimental results show that the proposed method improves the control bandwidth of the system by at least 3.6 times compared with proportional-integral (PI) control. In addition, under the same control bandwidth condition, compared with the Smith predictor and proportional-integral (PI-Smith) control method, the system is more capable of rejecting internal and external disturbances, and its dynamic response performance is improved by more than 29%.

Whole-brain monosynaptic inputs to lateral periaqueductal gray glutamatergic neurons in mice.

OBJECTIVE: The lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive behaviors. Currently, the whole-brain monosynaptic inputs to LPAG glutamatergic neurons are unknown. This study aims to explore the structural framework of the underlying neural mechanisms of LPAG glutamatergic neurons. METHODS: This study used retrograde tracing systems based on the rabies virus, Cre-LoxP technology, and immunofluorescence analysis. RESULTS: We found that 59 nuclei projected monosynaptic inputs to the LPAG glutamatergic neurons. In addition, seven hypothalamic nuclei, namely the lateral hypothalamic area (LH), lateral preoptic area (LPO), substantia innominata (SI), medial preoptic area, ventral pallidum, posterior hypothalamic area, and lateral globus pallidus, projected most densely to the LPAG glutamatergic neurons. Notably, we discovered through further immunofluorescence analysis that the inputs to the LPAG glutamatergic neurons were colocalized with several markers related to important neurological functions associated with physiological behaviors. CONCLUSION: The LPAG glutamatergic neurons received dense projections from the hypothalamus, especially nuclei such as LH, LPO, and SI. The input neurons were colocalized with several markers of physiological behaviors, which show the pivotal role of glutamatergic neurons in the physiological behaviors regulation by LPAG.

Prevalence of nonalcoholic fatty liver disease and the related risk factors among healthy adults: A cross-sectional study in Chongqing, China.

Background: Epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in Chongqing, a west-central city of China, remain unclear. The objective of this study was to investigate the prevalence of NAFLD and the related risk factors among healthy adults for physical examination in Chongqing. Methods: A total of 110,626 subjects were enrolled in the present study. Each of the participants underwent physical examination, laboratory measurements, and abdominal ultrasonography. The chi-square test was employed to compare differences in the NAFLD prevalence, and logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD. Results: The prevalence of NAFLD in individuals in the population of Chongqing was 28.5%, and the prevalence in men (38.1%) was significantly higher than that in women (13.6%) (OR = 2.44; 95% CI: 2.31-2.58). NAFLD was more common in men aged 51-60 years and women over 60 years. Approximately 79.1% of the people with obesity and 52.1% of the people with central obesity had NAFLD. The prevalence of NAFLD in people with hypertension and cholelithiasis was 48.9 and 38.4%, respectively. Logistic regression showed that gender, age, body max index (BMI), central obesity, hypertension, impaired fasting glucose/diabetes mellitus (DM), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hyperuricemia (HUA), alanine transaminase (ALT), and cholelithiasis were independently associated with the presence of NAFLD. Conclusion: The prevalence of NAFLD among healthy adults in Chongqing was high. To improve the prevention and management of NAFLD, special attention should be paid to the factors associated with the presence of NAFLD, including higher BMI, higher waist circumference, higher blood glucose, hypertension, hypertriglyceridemia, hyperuricemia, cholelithiasis, and elevated ALT.

Intracavity adaptive correction of an unstable standing-wave resonator based on reconstruction matrix optimization.

Due to the existence of the expanding beam portion in the positive branch confocal unstable resonator, the laser passes through the intracavity deformable mirror (DM) twice with different apertures, which makes it complicated to calculate the required compensation surface of the DM. In this paper, an adaptive compensation method for intracavity aberrations based on reconstruction matrix optimization is proposed to solve this problem. A collimated probe laser of 976 nm and a Shack-Hartmann wavefront sensor (SHWFS) are introduced from the outside of the resonator to detect intracavity aberrations. The feasibility and effectiveness of this method are verified by numerical simulations and the passive resonator testbed system. By adopting the optimized reconstruction matrix, the control voltages of the intracavity DM can be directly calculated from the SHWFS slopes. After compensation by the intracavity DM, the beam quality ß of the annular beam coupled out from the scraper is improved from 6.2 times diffraction limit to 1.6 times diffraction limit.

Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation.

Sleep, torpor, and hibernation are three distinct hypometabolic states. However, they have some similar physiological features, such as decreased core body temperature and slowing heart rate. In addition, the accumulation of adenosine seems to be a common feature before entry into these three states, suggesting that adenosine and its receptors, also known as P1 receptors, may mediate the initiation and maintenance of these states. This review, therefore, summarizes the current research on the roles and possible neurobiological mechanisms of adenosine and P1 receptors in sleep, torpor, and hibernation. Understanding these aspects will give us better prospects in sleep disorders, therapeutic hypothermia, and aerospace medicine.

Global ubiquitinome analysis reveals the role of E3 ubiquitin ligase FaBRIZ in strawberry fruit ripening.

Ubiquitination is an important post-translational modification that mediates protein degradation in eukaryotic cells, participating in multiple biological processes. However, the profiling of protein ubiquitination and the function of this crucial modification in fruit ripening remain largely unknown. In this study, we found that suppression of proteasome by the inhibitor MG132 retarded strawberry fruit ripening. Using K-ɛ-GG antibody enrichment combined with high-resolution mass spectrometry, we performed a comprehensive ubiquitinome analysis in strawberry fruit. We identified 2947 ubiquitination sites for 2878 peptides within 1487 proteins, which are involved in a variety of cellular functions. The lysine at position 48 (K48)-linked poly-ubiquitin chains appeared to be the most prevalent type of modification among the identified ubiquitinated proteins. A large number of ubiquitination sites exhibited altered ubiquitination levels after proteasome inhibition, including those within ripening-related proteins associated with sugar and acid metabolism, cell wall metabolism, anthocyanin synthesis, and ABA biosynthesis and signalling. We further demonstrated that FaBRIZ, a RING-type E3 ligase, functions as a negative regulator of ripening in strawberry fruit. Our findings highlight the critical regulatory roles of protein ubiquitination in fruit ripening. The ubiquitinome data provide a basis for further exploration of the function of ubiquitination on specific proteins.

Clinical characteristics of COVID-19 in young patients differ from middle-aged and elderly patients.

Introduction: Coronavirus disease-2019 (COVID-19) has spread worldwide. The study aimed to understand the clinical characteristics of young COVID-19 patients. Material and methods: Ninety patients with severe COVID-19 infection in western Chongqing were collected from 21 January to 14 March 2020. They were divided into 4 groups based on age: youth (< 39 years), middle-aged (39-48 years), middle-elderly aged (49-60 years), and elderly (> 60 years). The clinical symptoms, laboratory findings, imaging findings, and treatment effects were compared among the groups. Results: There were 22, 27, 19, and 22 cases in the youth, middle-aged, middle-elderly, and elderly groups, respectively. There were no significant differences with respect to gender or smoking status among the four groups. The clinical indicators of severe disease in the youth group were significantly different from the other three groups, and included the lymphocyte count (p < 0.001), C-reactive protein level (p = 0.03), interleukin-6 level (p = 0.01), chest computed tomography (CT) findings (p < 0.001), number of mild cases (p = 0.02), education level (p < 0.001), and CD4 + T lymphocyte level (p = 0.02) at the time of admission, and the pneumonia severity index (PSI) at the time of discharge (p < 0.001). The complications (p < 0.001) among the youth group were also significantly different from the other groups. Conclusions: Young patients have milder clinical manifestations, which may be related to higher education level, higher awareness and higher acceptance of the prevention and control of the COVID-19 epidemic, as well as their good immune function.

NIR Light-Triggered Quantitative Pulsed Drug Release.

Quantitative drug release is important for improving therapeutic efficiency and avoiding side effects. While using long-term delivery system for repeated therapies, it is indispensable but challenging to accurately control the drug dosing. Here, a photocleavable prodrug loaded hydrogel is proposed for near infrared (NIR) light-triggered quantitative pulsed drug release. IR783, a commercially available NIR fluorescent dye, is conjugated with methyl honokiol (mHNK) to give a photocleavable IR783-mHNK prodrug. Injectable glycol chitosan (GC) hydrogel is chosen as a reservoir, in which IR783-mHNK can be efficiently loaded via electrostatic and hydrophobic interactions. Upon 680 nm light-emitting diode (LED) light irradiation, IR783-mHNK cleaves and mHNK is released. Notably, it is found that IR783-mHNK presents synchronous photocleavage-fluorescence bleaching phenomenon. The released amount of mHNK is visible by measuring the residual fluorescent intensity of hydrogel. Quantitative drug release is achieved by controlling irradiation duration and the drug release process is visible by fluorescence imaging. The prodrug-loaded hydrogel shows good stability, minimum leakage and efficient light responsibility both in vitro and in vivo. After light triggering, monitorable quantitative mHNK release and on-demand sleep-promotiing effect are verified in mice without toxicities.

Cost-effectiveness analysis of nasojejunal tube feeding for the prevention of pneumonia in adults who are critically ill.

BACKGROUND: Nasojejunal tube (NJT) feeding has demonstrated value in reducing pneumonia in adults who are critically ill who require enteral nutrition (EN) support. This study discusses whether EN support via NJT feeding is more cost-effective than nasogastric tube (NGT) feeding in reducing pneumonia. METHODS: A decision-tree model was created. The analysis was based on data from a health care provider in China. Model inputs were derived from published data. The end points included incremental cost per pneumonia infection avoided, incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB), and incremental NMB (INMB) associated with prevention of pneumonia. The uncertainty was assessed through one-way and probabilistic sensitivity analysis. RESULTS: The base case analysis showed that EN support via NJT feeding resulted in 0.7453 quality-adjusted life years (QALYs) at a cost of $3018.83 compared with NGT feeding, which resulted in 0.7354 QALYs at a cost of $4788.76. NJT feeding was better than NGT feeding, providing an INMB of $2075.09 and an ICER of -$178,813.96 per QALY gained, and the cost per pneumonia infection prevented was $16,808.51. The probabilistic sensitivity analysis indicated that NJT feeding was more cost-effective in 83.4% of the cases, with a cost below the WTP threshold. The NMB and INMB estimation for different WTP thresholds also indicated that NJT feeding is the optimal strategy. CONCLUSIONS: EN support via NJT feeding was a more cost-effective strategy than NGT feeding in preventing pneumonia in adults who are critically ill.

Prevalence and associated metabolic factors for thyroid nodules: a cross-sectional study in Southwest of China with more than 120 thousand populations.

OBJECTIVE: To explore the prevalence and its associated metabolic factors of thyroid nodules (TNs) among subjects who participated in the physical examinations in Chongqing, China. METHODS: The participants from the Health Management Center of JinShan Hospital of Chongqing Medical University, between September 2015 and May 2020, were included in this study. All of the participants underwent thyroid ultrasonography, anthropometric measurements, and serum examinations. Differences in the TNs prevalence were compared with the chi-square test or Wilcoxon rang-sum test. Multivariable logistic regression analyses were used to estimate the metabolic factors associated with TNs and multiple thyroid nodules (MTNs). RESULTS: Of the included 121,702 participants, 41,547 had TNs, and 20,899 had MTNs, with the prevalence of 34.1 and 17.0 %, respectively. Women had a significantly higher prevalence of TNs than men (40.6 % vs. 29.8 %; χ2 = 1517.33, P < 0.001), and TNs prevalence was gradually increased with age (P for trend < 0.001). Female gender, advanced age, and metabolic factors including central obesity, hypertension, diabetes and fatty liver were positively associated with TNs; BMI, hyperlipoidemia and hyperuricemia were not independent risk factors of TNs. While female gender, advanced age, central obesity, hypertension and diabetes were independent risk factors of MTNs. CONCLUSIONS: The prevalence of thyroid nodules was relatively high. The associated factors identified in this study could help the clinicians to detect the high-risk patients and make targeted screening strategies for the preventing of the occurrence of TNs.

Decoupling control algorithm based on numerical orthogonal polynomials for a woofer-tweeter adaptive optics system.

To resolve cooperative control issues of dual wavefront correctors in generalized irregular pupil regions, we propose a decoupling control algorithm based on numerical orthogonal polynomials (NOP). The proposed algorithm firstly deduces NOP from Zernike polynomials in generalized irregular pupil regions. Then, according to wavefront restoration, different spatial frequency aberrations to different wavefront correctors are assigned precisely. Finally, the algorithm calculates and eliminates the cross-coupling between dual wavefront correctors. As observed in numerical simulations and experiments based on a typical woofer-tweeter (W-T) adaptive optics system, NOP decoupling control algorithm restrains the cross-coupling between woofer and tweeter in generalized irregular pupil regions. Moreover, there are obvious advantages over Zernike polynomials decoupling control algorithm in cross-coupling suppression for various scenarios in irregular pupil regions and restoration orders.

A meta-analysis on the role of pre-existing chronic disease in the cardiac complications of SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with multiple direct and indirect cardiovascular complications. We sought to analyze the association of host co-morbidities (chronic respiratory illnesses, cardiovascular disease [CVD], hypertension or diabetes mellitus [DM]) with the acute cardiovascular complications associated with SARS-CoV-2 infection. Individual analyses of the majority of studies found median age was higher by ~10 years in patients with cardiovascular complications. Pooled analyses showed development of SARS-CoV-2 cardiovascular complications was significantly increased in patients with chronic respiratory illness (odds ratio (OR): 1.67 [1.48, 1.88]), CVD (OR: 3.37 [2.57, 4.43]), hypertension (OR: 2.68 [2.11, 3.41]), DM (OR: 1.60 [1.31, 1.95]) and male sex (OR: 1.31 [1.21, 1.42]), findings that were mostly conserved during sub-analysis of studies stratified into global geographic regions. Age, chronic respiratory illness, CVD, hypertension, DM, and male sex may represent prognostic factors for the development of cardiovascular complications in COVID-19 disease, highlighting the need for a multidisciplinary approach to chronic disease patient management.

Functional redox links between lumen thiol oxidoreductase1 and serine/threonine-protein kinase STN7.

In response to changing light quantity and quality, photosynthetic organisms perform state transitions, a process which optimizes photosynthetic yield and mitigates photo-damage. The serine/threonine-protein kinase STN7 phosphorylates the light-harvesting complex of photosystem II (PSII; light-harvesting complex II), which then migrates from PSII to photosystem I (PSI), thereby rebalancing the light excitation energy between the photosystems and restoring the redox poise of the photosynthetic electron transport chain. Two conserved cysteines forming intra- or intermolecular disulfide bonds in the lumenal domain (LD) of STN7 are essential for the kinase activity although it is still unknown how activation of the kinase is regulated. In this study, we show lumen thiol oxidoreductase 1 (LTO1) is co-expressed with STN7 in Arabidopsis (Arabidopsis thaliana) and interacts with the LD of STN7 in vitro and in vivo. LTO1 contains thioredoxin (TRX)-like and vitamin K epoxide reductase domains which are related to the disulfide-bond formation system in bacteria. We further show that the TRX-like domain of LTO1 is able to oxidize the conserved lumenal cysteines of STN7 in vitro. In addition, loss of LTO1 affects the kinase activity of STN7 in Arabidopsis. Based on these results, we propose that LTO1 helps to maintain STN7 in an oxidized active state in state 2 through redox interactions between the lumenal cysteines of STN7 and LTO1.

Genome-wide binding analysis of the tomato transcription factor SlDof1 reveals its regulatory impacts on fruit ripening.

The DNA binding with one finger (Dof) proteins are plant-specific transcription factors involved in a variety of biological processes. However, little is known about their functions in fruit ripening, a flowering-plant-specific process that is required for seed maturation and dispersal. Here, we found that the tomato Dof transcription factor SlDof1, is necessary for normal fruit ripening. Knockdown of SlDof1 expression by RNA interference delayed ripening-related processes, including lycopene synthesis and ethylene production. Transcriptome profiling indicated that SlDof1 influences the expression of hundreds of genes, and a chromatin immunoprecipitation sequencing revealed a large number of SlDof1 binding sites. A total of 312 genes were identified as direct targets of SlDof1, among which 162 were negatively regulated by SlDof1 and 150 were positively regulated. The SlDof1 target genes were involved in a variety of metabolic pathways, and follow-up analyses verified that SlDof1 directly regulates some well-known ripening-related genes including ACS2 and PG2A as well as transcriptional repressor genes such as SlIAA27. Our findings provide insights into the transcriptional regulatory networks underlying fruit ripening and highlight a gene potentially useful for genetic engineering to control ripening.

Forelimb joints contribute to locomotor performance in reindeer (Rangifer tarandus) by maintaining stability and storing energy.

Reindeer (Rangifer tarandus) have lengthy seasonal migrations on land and their feet possess excellent locomotor characteristics that can adapt to complex terrains. In this study, the kinematics and vertical ground reaction force (GRF) of reindeer forelimb joints (interphalangeal joint b, metacarpophalangeal joint c, and wrist joint d) under walk, trot 1, and trot 2 were measured using a motion tracking system and Footscan pressure plates. Significant differences among different locomotor activities were observed in the joint angles, but not in changes of the joint angles (α b , α c , α d ) during the stance phase. Peak vertical GRF increased as locomotor speed increased. Net joint moment, power, and work at the forelimb joints were calculated via inverse dynamics. The peak joint moment and net joint power related to the vertical GRF increased as locomotor speed increased. The feet absorbed and generated more energy at the joints. During different locomotor activities, the contribution of work of the forelimbs changed with both gait and speed. In the stance phase, the metacarpophalangeal joint absorbed more energy than the other two joints while trotting and thus performed better in elastic energy storage. The joint angles changed very little (∼5°) from 0 to 75% of the stance phase, which reflected the stability of reindeer wrist joints. Compared to typical ungulates, reindeer toe joints are more stable and the stability and energy storage of forelimb joints contribute to locomotor performance in reindeer.

A Single Far-Field Deep Learning Adaptive Optics System Based on Four-Quadrant Discrete Phase Modulation.

In adaptive optics (AO), multiple different incident wavefronts correspond to a same far-field intensity distribution, which leads to a many-to-one mapping. To solve this problem, a single far-field deep learning adaptive optics system based on four-quadrant discrete phase modulation (FQDPM) is proposed. Our method performs FQDPM on an incident wavefront to overcome this many-to-one mapping, then convolutional neural network (CNN) is used to directly predict the wavefront. Numerical simulations indicate that the proposed method can achieve precise high-speed wavefront correction with a single far-field intensity distribution: it takes nearly 0.6ms to complete wavefront correction while the mean root mean square (RMS) of residual wavefronts is 6.3% of that of incident wavefronts, and the Strehl ratio of the far-field intensity distribution increases by 5.7 times after correction. In addition, the experiment results show that mean RMS of residual wavefronts is 6.5% of that of incident wavefronts and it takes nearly 0.5 ms to finish wavefront reconstruction, which verifies the correctness of our proposed method.

Liquid-Liquid Phase Transition Drives Intra-chloroplast Cargo Sorting.

In eukaryotic cells, organelle biogenesis is pivotal for cellular function and cell survival. Chloroplasts are unique organelles with a complex internal membrane network. The mechanisms of the migration of imported nuclear-encoded chloroplast proteins across the crowded stroma to thylakoid membranes are less understood. Here, we identified two Arabidopsis ankyrin-repeat proteins, STT1 and STT2, that specifically mediate sorting of chloroplast twin arginine translocation (cpTat) pathway proteins to thylakoid membranes. STT1 and STT2 form a unique hetero-dimer through interaction of their C-terminal ankyrin domains. Binding of cpTat substrate by N-terminal intrinsically disordered regions of STT complex induces liquid-liquid phase separation. The multivalent nature of STT oligomer is critical for phase separation. STT-Hcf106 interactions reverse phase separation and facilitate cargo targeting and translocation across thylakoid membranes. Thus, the formation of phase-separated droplets emerges as a novel mechanism of intra-chloroplast cargo sorting. Our findings highlight a conserved mechanism of phase separation in regulating organelle biogenesis.