Proteomic Profiling of Unannotated Microproteins in Human Placenta Reveals XRCC6P1 as a Potential Negative Regulator of Translation.

Ribosome profiling and mass spectrometry have revealed thousands of previously unannotated small and alternative open reading frames (sm/alt-ORFs) that are translated into micro/alt-proteins in mammalian cells. However, their prevalence across human tissues and biological roles remains largely undefined. The placenta is an ideal model for identifying unannotated microproteins and alt-proteins due to its considerable protein diversity that is required to sustain fetal development during pregnancy. Here, we profiled unannotated microproteins and alt-proteins in human placental tissues from preeclampsia patients or healthy individuals by proteomics, identified 52 unannotated microproteins or alt-proteins, and demonstrated that five microproteins can be translated from overexpression constructs in a heterologous cell line, although several are unstable. We further demonstrated that one microprotein, XRCC6P1, associates with translation initiation factor eIF3 and negatively regulates translation when exogenously overexpressed. Thus, we revealed a hidden sm/alt-ORF-encoded proteome in the human placenta, which may advance the mechanism studies for placenta development as well as placental disorders such as preeclampsia.

Multi-elemental stoichiometric ratios of atmospheric wet deposition in Chinese terrestrial ecosystems.

Intense human activities have significantly altered the concentrations of atmospheric components that enter ecosystems through wet and dry deposition, thereby affecting elemental cycles. However, atmospheric wet deposition multi-elemental stoichiometric ratios are poorly understood, hindering systematic exploration of atmospheric deposition effects on ecosystems. Monthly precipitation concentrations of six elements-nitrogen (N), phosphorus (P), sulfur (S), potassium (K), calcium (Ca), and magnesium (Mg)-were measured from 2013 to 2021 by the China Wet Deposition Observation Network (ChinaWD). The multi-elemental stoichiometric ratio of atmospheric wet deposition in Chinese terrestrial ecosystems was N: K: Ca: Mg: S: P = 31: 11: 67: 5.5: 28: 1, and there were differences between vegetation zones. Wet deposition N: S and N: Ca ratios exhibited initially increasing then decreasing inter-annual trends, whereas N: P ratios did not exhibit significant trends, with strong interannual variability. Wet deposition of multi-elements was significantly spatially negatively correlated with soil nutrient elements content (except for N), which indicates that wet deposition could facilitate soil nutrient replenishment, especially for nutrient-poor areas. Wet N deposition and N: P ratios were spatially negatively correlated with ecosystem and soil P densities. Meanwhile, wet deposition N: P ratios were all higher than those of ecosystem components (vegetation, soil, litter, and microorganisms) in different vegetation zones. High input of N deposition may reinforce P limitations in part of the ecosystem. The findings of this study establish a foundation for designing multi-elemental control experiments and exploring the ecological effects of atmospheric deposition.

Construction and application of fetal loss risk model in systemic lupus erythematosus patients with mild disease severity.

BACKGROUND: This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. METHODS: An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787-0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. CONCLUSION: The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Chemical labeling and proteomics for characterization of unannotated small and alternative open reading frame-encoded polypeptides.

Thousands of unannotated small and alternative open reading frames (smORFs and alt-ORFs, respectively) have recently been revealed in mammalian genomes. While hundreds of mammalian smORF- and alt-ORF-encoded proteins (SEPs and alt-proteins, respectively) affect cell proliferation, the overwhelming majority of smORFs and alt-ORFs remain uncharacterized at the molecular level. Complicating the task of identifying the biological roles of smORFs and alt-ORFs, the SEPs and alt-proteins that they encode exhibit limited sequence homology to protein domains of known function. Experimental techniques for the functionalization of these gene classes are therefore required. Approaches combining chemical labeling and quantitative proteomics have greatly advanced our ability to identify and characterize functional SEPs and alt-proteins in high throughput. In this review, we briefly describe the principles of proteomic discovery of SEPs and alt-proteins, then summarize how these technologies interface with chemical labeling for identification of SEPs and alt-proteins with specific properties, as well as in defining the interactome of SEPs and alt-proteins.

Phosphorus level impacts luteolin effect on Microcystis aeruginosa growth and microcystin-pollution risk - Novel perspective from correlation between exopolymers substances fractions and microcystin-production/release.

Luteolin as a phytogenic algicide can inhibit the growth and microcystins (MCs) release of Microcystis, a dominant genus during cyanobacterial blooms, but how phosphorus (P) level impacts luteolin effect on its growth and MC-pollution risk is unclear. By employing Microcystis aeruginosa as test alga, this study addressed this concern and explored response mechanisms from novel insights of relationship between extracellular polysaccharide (ex-poly) and protein (ex-pro) contents and MC-production/release. At each P level (0.05-5 mg/L), rising luteolin dose more greatly inhibited Microcystis growth and MC-pollution risk, with growth inhibition ratio of around 10%-30%, 20%-50% and 40%-90% for 3, 6 and 12 mg/L luteolin, respectively, but almost increasingly enhanced cellular ability of MC-production/conservation and total and bound ex-poly/ex-pro production. Rising P level promoted Microcystis growth and intracellular/extracellular MCs content (IMC, EMC) in test system at each luteolin dose, thus higher P level weakened algicidal and MC-removal effects of luteolin, indicating that P-decrease was required for stronger application outcome of luteolin. Total and bound ex-poly/ex-pro amount were positively correlated with cellular MC-production/conservation ability, IMC and EMC, which constituted cooperative stress-defense of Microcystis at each P level. Besides, rising luteolin dose posed stronger algicidal effect by inactivating gene expression involving peroxidase synthesis (especially at P-limitation), photosynthesis and P acquisition, while rising P level alleviated algicidal and MC-pollution inhibition effects of luteolin by enhancing gene expression involving N acquisition and peroxidase synthesis. This study shed novel insights for P-dependent effect and mechanisms of luteolin on toxigenic Microcystis growth and MC-pollution control, which guided to mitigating toxigenic Microcystis-dominated cyanobacterial blooms in different P-level water areas.

Highly Efficient Synthesis of Chlorogenic Acid Oleyl Alcohol Ester under Non-Catalytic and Solvent-Free Conditions.

As a natural polyphenolic compound, chlorogenic acid (CGA) has attracted increasing attention for its various biological activities, such as antioxidant, liver protection, intestinal barrier protection, and effective treatment of obesity and type II diabetes. However, the poor solubility of CGA in hydrophobic media limits its application in the food, drug and cosmetic industries. In order to obtain new hydrophobic derivatives, a highly efficient synthesis approach of CGA oleyl alcohol ester (CGOA) under non-catalytic and solvent-free conditions was developed in this study. The influences of reaction temperature, reaction time, substrate molar ratio, and stirring rate on the CGA conversion were investigated. The results showed that the optimal conditions were as follows: reaction temperature 200 °C, reaction time 3 h, molar ratio of CGA to oleyl alcohol 1:20, and stirring rate 200 rpm. Under these conditions, the CGA conversion could reach 93.59%. Then, the obtained crude product was purified by solvent extraction and column chromatography, and the purify of CGOA was improved to 98.72%. Finally, the structure of CGOA was identified by FT-IR, HPLC-MS and NMR. This study provides a simple and efficient strategy for the preparation of CGOA with the avoidance of catalysts and solvents.

Increased or decreased? Interpersonal neural synchronization in group creation.

Group creation is the process by which group members collaborate to produce novel and useful ideas or products, including ideas generation and evaluation. However, the interpersonal neural mechanism of group creation during natural communication remains unclear. In this study, two groups of same-sex dyads with similar individual creativity collaborated to complete the Product Improvement Task (creative condition) and the Item Purchase Plan Task (control condition), respectively. Functional near-infrared spectroscopy (fNIRS) was used to record both members' neural activity in the left prefrontal (lPFC) and right temporal-parietal junction (rTPJ) regions during the task. Considering that the role asymmetry of group members may have an impact on interpersonal neural patterns, we identified leaders and followers in the dyads based on participant performance. The results showed that leaders and followers in the creative condition had significantly lower interpersonal neural synchronization (INS) in the right superior temporal gyrus-left superior frontal gyrus, right supramarginal gyrus-left superior frontal gyrus, and right supramarginal gyrus-left middle frontal gyrus than in the control condition. Partial multivariate Granger causality analyses revealed the influence between dyads was bidirectional but was significantly stronger from the leaders to the followers than the other direction. In addition, in the creative task, the INS was significantly associated with novelty, appropriateness, and conflict of views. All these findings suggest that the ideas generation and ideas evaluation process in group creation have poor interpersonal neural activity coupling due to factors such as the difficulty of understanding novel ideas. However, performances may be improved when groups can better integrate views and reach collective understanding, intentions, and goals. Furthermore, we found that there are differences in the dynamics of INS in different brain regions. The INS related to the novelty of the group creation decreased in the early stages, while the INS related to the appropriateness decreased in the middle stages. Our findings reveal a unique interpersonal neural pattern of group creation processes in the context of natural communication.

Detection of Gastric Cancer-Associated d-Amino Acids and Carcinoembryonic Antigen by Colorimetric and Immuno ECL Sensing Platform Based on the Catalysis of N/S-Doped Carbon Dots @ N-Rich Porous Carbon Nanoenzyme.

Gastric cancer is a malignant tumor, and its early diagnosis remains challenging due to the lack of simple and sensitive detection methods and specific biomarkers. In this work, to improve the detection reliability, we developed a dual-mode detection strategy for the detection of two biomarkers associated with it. First, an N- and S-doped carbon dots-N-rich porous carbon nanoenzyme (N/S-CDs@NC) was prepared by a two-step pyrolysis of thiourea-penetrated zinc-based zeolite imidazole framework. It was then combined with the 3,3',5,5'-tetramethylbenzidine-H2O2 system for the colorimetric detection of d-amino acids (i.e., d-proline (d-Pro) and d-alanine (d-Ala)) in saliva, based on d-amino acid oxidase catalyzing d-amino acid oxidation to produce H2O2. In this way, the low detection limits (S/N = 3) of d-Pro and d-Ala were 0.14 and 0.35 µM, respectively. Furthermore, N/S-CDs@NC was combined with the luminol-H2O2 electrochemiluminescence (ECL) system and magnetic immune accumulation/separation strategy to detect the carcinoembryonic antigen (CEA) in serum. The porous N/S-CDs@NC could facilitate participant contact, promote the generation of hydroxyl radical (•OH), and electrostatically attract •OH, thereby significantly amplifying the ECL signal of luminol and improving the signal stability. Thus, the detection mode showed considerable sensitivity and selectivity, with a low detection limit of 0.26 pg mL-1. The strategy proposed in this work can also be used for the detection of other disease markers by substituting the recognition elements, thus having good application potential.

Atmospheric Wet Iron, Molybdenum, and Vanadium Deposition in Chinese Terrestrial Ecosystems.

Iron (Fe), molybdenum (Mo), and vanadium (V) are the main components of the three known biological nitrogenases, which constrain nitrogen fixation and affect ecosystem productivity. Atmospheric deposition is an important pathway of these trace metals into ecosystems. Here, we explored the deposition flux, spatiotemporal pattern, and influencing factors of atmospheric wet Fe, Mo, and V deposition based on China Wet Deposition Observation Network (ChinaWD) data from 2016 to 2020. Our results showed that atmospheric wet Fe, Mo, and V deposition was 7.77 ± 7.24, 0.16 ± 0.11, and 0.13 ± 0.12 mg m-2 a-1 in Chinese terrestrial ecosystems, respectively, and revealed obvious spatial patterns but no significant annual trends. Wet Fe deposition was significantly correlated with the soil Fe content. Mo and V deposition was more affected by anthropogenic activities than Fe deposition. Wet Mo deposition was significantly affected by Mo ore reserves and waste incineration. V deposition was significantly correlated with domestic biomass burning. This study quantified wet Fe, Mo, and V deposition in China for the first time, and the implications of atmospheric trace metal deposition on biological nitrogen fixation were discussed.

Atmospheric silicon wet deposition and its influencing factors in China.

Silicon (Si) is considered a "quasi-essential" nutrient element for plants and is also an essential nutrient for some phytoplankton. Except for the silicate provided by weathering, atmospheric deposition has gradually become an important supplementary method for Si nutrients to enter the ecosystem. However, national observational studies on atmospheric silicon deposition have not yet been reported. Herein, based on the China Wet Deposition Observation Network, we continuously collected monthly wet deposition samples from 43 typical ecosystems from 2013 to 2020 and measured the content of dissolved silica (dSi) in precipitation to quantify the spatiotemporal patterns of Si wet deposition in China. The results showed that the mean annual dSi wet deposition in China during 2013-2020 was approximately 2.07 ± 0.27 kg ha-1 yr-1. Atmospheric dSi deposition was higher in Southwest, North, and South China but lower in the Northwest and Northeast China, which was mainly regulated by precipitation and soil available Si content. There was no significant annual variation trend in dSi deposition during 2013-2020 in China, which showed disorderly fluctuations from year to year. This study revealed the spatiotemporal patterns of atmospheric dSi deposition in China for the first time, which can provide unique scientific data to explore the potential effect of dSi deposition on carbon sequestration in aquatic ecosystems. A comprehensive evaluation of the nutrient balance of aquatic ecosystems from the perspective of nitrogen, phosphorus, and silicon stoichiometry is required in the future.

Simulation of emission reduction path under the path of differentiated energy transformation in China's industrial cities: a case study of Shanghai.

The formulation of long-term step-by-step emission reduction plan is an important step for effective scientific emission reduction. This paper takes Shanghai as the research object, constructs PSO-LSTM model on the basis of STIRPAT model, and further constructs three dynamic policy scenarios combined with China's actual situation and makes short-, medium-, and long-term multivariate predictions for them. The study finds that only the improvement of energy consumption structure has a promotion effect on carbon emission reduction, and urbanization, industrial structure, technology level, population, and economic level all have an increasing effect, and secondly, the carbon emission reduction path of Shanghai basically achieves the core objective of steady decrease under the three scenarios. Secondly, under the three scenarios, Shanghai's carbon emission reduction path basically achieves the core objective of steady decline, but the decline in the GU scenario is more significant. It is recommended that Shanghai further adjusts its industrial structure, optimizes its energy consumption structure, promotes technological innovation and progress, and promotes the development of the circular economy model.

A liposome encapsulated methylene blue-mediated electrochemical and UV-visible dual mode split-type immunoassay for the detection of 17ß-estradiol.

Herein, we fabricated an electrochemical (EC) and UV-visible absorption (UV-vis) dual mode split-type immunoassay for the detection of 17ß-estradiol (E2), which was mediated by liposome encapsulated methylene blue (MB@lip). MB molecule acted as the probe in the EC and UV-vis absorption dual mode detections, and its release was controlled by liposome. The competitive immune recognition was conducted between the E2 in the sample and E2 conjugated bovine serum protein (E2-BSA) adsorbed on the 96-wells plate in combining with E2 antibody labeled with MB@lip (E2-Ab/MB@lip). MB molecule could be released from the resulting immune composite of E2-BSA/E2-Ab/MB@lip in the presence of Triton X-100, and quantified by UV-vis and EC methods. The three-dimensional cross-linked reduced graphene oxide/Ti3C2 (3D-rGO/Ti3C2) aerogel was prepared through hydrothermal method, then complexed with the electroactive anthraquinone (AQ) and used as the electrode modified material. The AQ/3D-rGO/Ti3C2 composite had high surface area and provided abundant adsorption sites for MB, and the displacement/competitive behavior between AQ and MB could dexterously achieve the ratiometric EC detection of E2. In addition, the inherent blue color of MB allowed it to be analyzed by UV-vis absorption method. The proposed dual mode detection method exhibited broad linear ranges of 0.1 pg mL-1 to 50 ng mL-1 (by UV-vis) and 0.03 pg mL-1 to 50 ng mL-1 (by EC) for E2 detection, and the detection limits were 0.023 pg mL-1 (S/N = 3) and 8.0 fg mL-1 (S/N = 3), respectively. Moreover, the proposed immunoassay exhibited good practicability and was applied to monitor E2 in milk and serum successfully.

Drug pair of Cornus officinalis and Radix achyranthis bidentatae improves renal injury of hypertension by regulating metabolic reprogramming mediated by eNOS.

Objective: To explore the effects and possible mechanisms of the drug pair Cornus officinalis and Radix achyranthis bidentatae (SYR-NX) on improving hypertensive kidney damage. Method: SYR-NX, a formulation of Cornus officinalis and Radix Achyranthis Bidentatae with a dose ratio 1:2.5, was used in this experiment. We investigated the effects of SYR-NX on spontaneously hypertensive rats (SHR) fed with a high-salt diet and Human Kidney-2 (HK2) cells exposed to hypoxia. After 8 weeks of treatment with SYR-NX, blood pressure was tested, and ß 2-Microglobulin(ß2-MG), blood creatinine (S-cr), endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH), M2 pyruvate kinase (PKM2), adenosine triphosphate (ATP), pyruvate, lactate, connective tissue growth factor (CTGF) and tumor necrosis factor-α (TNF-α)were measured. HK2 cells pre-treated with SYR-NX were cultured in a three-gas hypoxic incubator chamber (5 % CO2, 1 % O2, 94 % N2) for 12 h, and then eNOS, PKM2, NADPH, ATP, pyruvate, lactate, CTGF and TNF-α were assessed. Results: SYR-NX significantly reduced SBP, DBP, ß2-MG, S-cr, PKM2, pyruvate, lactate, CTGF and TNF-α, and increased eNOS, NADPH, and ATP. Conclusion: SYR-NX can regulate metabolic reprogramming through eNOS and improves hypertensive kidney injury.

Stilbene glycosides alleviate atherosclerosis partly by promoting lipophagy of dendritic cells.

Atherosclerosis (AS) is a chronic inflammatory disease resulting from lipid metabolism disorders and immune imbalances. Dendritic cells (DCs) are key cells that regulate adaptive and adaptive immunity. When DCs engulf excessive amounts lipids, their function is altered, thereby, accelerating the inflammatory process of AS. Cellular lipophagy serves to reduce lipid accumulation and maintain cellular lipid metabolism balance. In this study, we investigated the effectiveness of 2,3,5,4'-tetrahydroxystilbene 2-O-ß-D-glucoside (TSG) in intervening in the promotion of DCs lipid accumulation by ox-LDL, as well as its role in downregulating lipophagy. Our findings indicate that TSG reduces the maturity of DCs and promotes the differentiation of T cells towards Treg, thereby correcting the imbalanced Treg/Th17. These effects of TSG are closely associated with its inhibition of the PI3K-AKT-mTOR signaling pathway. After administering TSG to ApoE-/- mice that were fed a high-fat diet, there was a noticeable decrease in harmful blood lipids found in the serum. Additionally, the imbalanced Treg/Th17 levels in the spleen were restored, and the levels of pro-inflammatory factor IL-6 and IL-17A in the serum decreased, while the level of anti-inflammatory factor IL-10 increased. Furthermore, the arterial DCs showed a decrease in P62 content. Ultimately, these changes resulted in a reduction in plaque area. It is worth noting that the autophagy inhibitor chloroquine significantly altered the effects of TSG on ApoE-/- mice. In conclusion, this study reveals that TSG can alleviate AS. This is partly achieved through the activation of autophagy in DCs. By intervening in the lipophagy of DCs, it is possible to regulate the immune function of these cells, which in turn helps control the inflammation associated with AS. This presents a potential method for intervening in AS.

BONCAT-based Profiling of Nascent Small and Alternative Open Reading Frame-encoded Proteins.

RIBO-seq and proteogenomics have revealed that mammalian genomes harbor thousands of unannotated small and alternative open reading frames (smORFs, <100 amino acids, and alt-ORFs, >100 amino acids, respectively). Several dozen mammalian smORF-encoded proteins (SEPs) and alt-ORF-encoded proteins (alt-proteins) have been shown to play important biological roles, while the overwhelming majority of smORFs and alt-ORFs remain uncharacterized, particularly at the molecular level. Functional proteomics has the potential to reveal key properties of unannotated SEPs and alt-proteins in high throughput, and an approach to identify SEPs and alt-proteins undergoing regulated synthesis should be of broad utility. Here, we introduce a chemoproteomic pipeline based on bio-orthogonal non-canonical amino acid tagging (BONCAT) (Dieterich et al., 2006) to profile nascent SEPs and alt-proteins in human cells. This approach is able to identify cellular stress-induced and cell-cycle regulated SEPs and alt-proteins in cells. Graphical abstract Schematic overview of BONCAT-based chemoproteomic profiling of nascent, unannotated small and alternative open reading frame-encoded proteins (SEPs and alt-proteins).

Atmospheric wet organic nitrogen deposition in China: Insights from the national observation network.

Organic nitrogen (N) is an important component of atmospheric reactive N deposition, and its bioavailability is almost as important as that of inorganic N. Currently, there are limited reports of national observations of organic N deposition; most stations are concentrated in rural and urban areas, with even fewer long-term observations of natural ecosystems in remote areas. Based on the China Wet Deposition Observation Network, this study regularly collected monthly wet deposition samples from 43 typical ecosystems from 2013 to 2021 and measured related N concentrations. The aim was to provide a more comprehensive assessment of the multi-component characteristics of atmospheric wet N deposition and reveal the influencing factors and potential sources of wet dissolved organic N (DON) deposition. The results showed that atmospheric wet deposition fluxes of NO3-, NH4+, DON and dissolved total N (DTN) were 4.68, 5.25, 4.32, and 13.05 kg N ha-1 yr-1, respectively, and that DON accounted for 30 % of DTN deposition (potentially up to 50 % in remote areas). Wet DON deposition was related to anthropogenic emissions (agriculture, biomass burning, and traffic), natural emissions (volatile organic compound emissions from vegetation), and precipitation processes. The wet DON deposition flux was higher in South, Central, and Southwest China, with more precipitation and intensive agricultural activities or more vegetation cover, and lower in Northwest China and Inner Mongolia, with less precipitation and human activities or vegetation cover. DON was the main contributor to DTN deposition in remote areas and was possibly related to natural emissions. In rural and urban areas, DON may have been more influenced by agricultural activities and anthropogenic emissions. This study quantified the long-term spatiotemporal patterns of wet N deposition and provides a reference for future N addition experiments and N cycle studies. Further consideration of DON deposition is required, especially in the context of anthropogenic control of NO2 and NH3.

Unannotated microprotein EMBOW regulates the interactome and chromatin and mitotic functions of WDR5.

The conserved WD40-repeat protein WDR5 interacts with multiple proteins both inside and outside the nucleus. However, it is currently unclear whether and how the distribution of WDR5 between complexes is regulated. Here, we show that an unannotated microprotein EMBOW (endogenous microprotein binder of WDR5) dually encoded in the human SCRIB gene interacts with WDR5 and regulates its binding to multiple interaction partners, including KMT2A and KIF2A. EMBOW is cell cycle regulated, with two expression maxima at late G1 phase and G2/M phase. Loss of EMBOW decreases WDR5 interaction with KIF2A, aberrantly shortens mitotic spindle length, prolongs G2/M phase, and delays cell proliferation. In contrast, loss of EMBOW increases WDR5 interaction with KMT2A, leading to WDR5 binding to off-target genes, erroneously increasing H3K4me3 levels, and activating transcription of these genes. Together, these results implicate EMBOW as a regulator of WDR5 that regulates its interactions and prevents its off-target binding in multiple contexts.

The Impact of Extreme Temperature Shocks on the Health Status of the Elderly in China.

With the accelerating process of climate change, long-term exposure to extreme temperatures could threaten individuals' physical health, especially for the vulnerable population. This paper aims to investigate the long-term effects of extreme temperature exposure on the health of the elderly in the context of climate change and aging. Different from most of the existing literature in environmental economics, we define the relative extreme temperature exposure based on the local temperature pattern. By combining a large national household survey and nationwide meteorologic historical data, this study provides empirical evidence that heat exposure days and cold exposure days during the past year both significantly affect the physical health of middle-aged and elderly groups, controlling for city, year, and individual fixed effects. The effect on individual physical health has certain seasonal characteristics and is heterogeneous across populations. Additionally, cooling and heating equipment are effective in alleviating the reverse impact of heat and cold exposure. The estimation is robust and consistent across a variety of temperature measurements and model modifications. Our findings provide evidence of the long-term and accumulative cost of extreme temperature to middle-aged and elderly human capital, contributing to helping the public to better understand the full impact of climate change.

The impact of Children's gender on Parent's mental health and cognition -- evidence from China.

With the growing and aging population round the world, it becomes increasingly important to understand what factors impact the mental health and cognition of the older generations in order to design effective interventions. In this paper, we investigate the effect of a child's gender on parental mental health and cognition in the context of one of the world's largest developing countries and the unique one-child policy, using China Family Panel Studies (CFPS). We exploit the exogeneity of the first child's gender and find that having a son has significant protective effects on parents' mathematics performance and memory functions in one-child families, but such effects are absent in multi-child families. Moreover, we find that the protective effect is more pronounced among one-child families in rural areas than urban areas. Our results suggest the existence of gender inequality in China and reveal the hidden long-term social cost of the one-child policy.