SMURF2 predisposes cancer cell toward ferroptosis in GPX4-independent manners by promoting GSTP1 degradation.

Ferroptosis is a non-apoptotic form of regulated cell death. Glutathione (GSH) peroxidase 4 (GPX4) and GSH-independent ferroptosis suppressor protein 1 (FSP1) have been identified as major defenses. Here, we uncover a protective mechanism mediated by GSH S-transferase P1 (GSTP1) by monitoring proteinomic dynamics during ferroptosis. Dramatic downregulation of GSTP1 is caused by SMURF2-mediated GSTP1 ubiquitination and degradation at early stages of ferroptosis. Intriguingly, GSTP1 acts in GPX4- and FSP1-independent manners by catalyzing GSH conjugation of 4-hydroxynonenal and detoxifying lipid hydroperoxides via selenium-independent GSH peroxidase activity. Genetic modulation of the SMURF2/GSTP1 axis or the pharmacological inhibition of GSTP1's catalytic activity sensitized tumor responses to Food and Drug Administration (FDA)-approved ferroptosis-inducing drugs both in vitro and in vivo. GSTP1 expression also confers resistance to immune checkpoint inhibitors by blunting ferroptosis. Collectively, these findings demonstrate a GPX4/FSP1-independent cellular defense mechanism against ferroptosis and suggest that targeting SMURF2/GSTP1 to sensitize cancer cells to ferroptosis has potential as an anticancer therapy.

ER-associated degradation ligase HRD1 links ER stress to DNA damage repair by modulating the activity of DNA-PKcs.

Proteostasis and genomic integrity are respectively regulated by the endoplasmic reticulum-associated protein degradation (ERAD) and DNA damage repair signaling pathways, with both pathways essential for carcinogenesis and drug resistance. How these signaling pathways coordinate with each other remains unexplored. We found that ER stress specifically induces the DNA-PKcs-regulated nonhomologous end joining (NHEJ) pathway to amend DNA damage and impede cell death. Intriguingly, sustained ER stress rapidly decreased the activity of DNA-PKcs and DNA damage accumulated, facilitating a switch from adaptation to cell death. This DNA-PKcs inactivation was caused by increased KU70/KU80 protein degradation. Unexpectedly, the ERAD ligase HRD1 was found to efficiently destabilize the classic nuclear protein HDAC1 in the cytoplasm, by catalyzing HDAC1's polyubiquitination at lysine 74, at a late stage of ER stress. By abolishing HDAC1-mediated KU70/KU80 deacetylation, HRD1 transmits ER signals to the nucleus. The resulting enhanced KU70/KU80 acetylation provides binding sites for the nuclear E3 ligase TRIM25, resulting in the promotion of polyubiquitination and the degradation of KU70/KU80 proteins. Both in vitro and in vivo cancer models showed that genetic or pharmacological inhibition of HADC1 or DNA-PKcs sensitizes colon cancer cells to ER stress inducers, including the Food and Drug Administration-approved drug celecoxib. The antitumor effects of the combined approach were also observed in patient-derived xenograft models. These findings identify a mechanistic link between ER stress (ERAD) in the cytoplasm and DNA damage (NHEJ) pathways in the nucleus, indicating that combined anticancer strategies may be developed that induce severe ER stress while simultaneously inhibiting KU70/KU80/DNA-PKcs-mediated NHEJ signaling.

Genomic Mechanisms of Physiological and Morphological Adaptations of Limestone Langurs to Karst Habitats.

Knowledge of the physiological and morphological evolution and adaptation of nonhuman primates is critical to understand hominin origins, physiological ecology, morphological evolution, and applications in biomedicine. Particularly, limestone langurs represent a direct example of adaptations to the challenges of exploiting a high calcium and harsh environment. Here, we report a de novo genome assembly (Tfra_2.0) of a male François's langur (Trachypithecus francoisi) with contig N50 of 16.3 Mb and resequencing data of 23 individuals representing five limestone and four forest langur species. Comparative genomics reveals evidence for functional evolution in genes and gene families related to calcium signaling in the limestone langur genome, probably as an adaptation to naturally occurring high calcium levels present in water and plant resources in karst habitats. The genomic and functional analyses suggest that a single point mutation (Lys1905Arg) in the α1c subunit of the L-type voltage-gated calcium channel Cav1.2 (CACNA1C) attenuates the inward calcium current into the cells in vitro. Population genomic analyses and RNA-sequencing indicate that EDNRB is less expressed in white tail hair follicles of the white-headed langur (T. leucocephalus) compared with the black-colored François's langur and hence might be responsible for species-specific differences in body coloration. Our findings contribute to a new understanding of gene-environment interactions and physiomorphological adaptative mechanisms in ecologically specialized primate taxa.

Optical spanner for nanoparticle rotation with focused optical vortex generated through a Pancharatnam-Berry phase metalens.

Based on the focused optical vortex (OV) generated by a metalens, we studied the physical mechanism for optical manipulation of metal (Ag) nanoparticles in the orbital angular momentum (OAM) field. We found that metal nanoparticles can be stably trapped inside the OV ring and rotated by the azimuthal driving force originating from OAM transfer. The azimuthal force and rotation speed are directly and inversely proportional to the particle size, respectively. The torque for the same particle at the OV ring increases with the increase of the topological charge of the metalens. Considering the same topological charge, the radius of the OV ring or the range of the optical spanner has a positive correlation with the focal length. These kinds of optical tweezers by vortex metalenses can be used as an optical spanner or micro-rotor for lab-on-chip applications.

An improved spatial subsidy approach for ecological compensation in coastal seascapes for resilient land-sea management.

Human activities are considered a critical impact factor for decision-making in coupled human-nature systems, such as conservation of coastal systems. Identifying key human activities that cause significant habitat degradation for coastal species remains challenging. We improved the spatial subsidy approach to identify and prioritize control strategies for human-caused distribution shifts of marine species. We applied this method to a threatened Indo-Pacific humpback dolphin (Sousa chinensis) in Xiamen Bay, China. Our results indicate that (1) a significant distribution shift for humpback dolphins from existing nature reserves to peripheral waters occurred from 2011 to 2014; (2) coastal tourism and industrial and urban construction had more significant negative impacts on humpback dolphins than maritime transportation and reclamation; and (3) proactive management should be implemented for maritime transportation and reclamation, while reactive management should be implemented for coastal tourism and industrial and urban construction. Human impact analysis, combined with spatially explicit modeling, contributes to determining the spatial alternatives for conservation planning. In response to possible ecological damage caused by human activities, the improved spatial subsidy results help provide knowledge and platforms for ecological compensation.

Characterization particulate matter from several Chinese cooking dishes and implications in health effects.

Cooking fume produced by oil and food at a high temperature releases large amount of fine particulate matter (PM) which have a potential hazard to human health. This chamber study investigated particle emission characteristics originated from using four types of oil (soybean oil, olive oil, peanut oil and lard) and different kinds of food materials (meat and vegetable). The corresponding emission factors (EFs) of number, mass, surface area and volume for particles were discussed. Temporal variation of size-fractionated particle concentration showed that olive oil produced the highest number PM concentration for the entire cooking process. Multiple path particle dosimetry (MPPD) model was performed to predict deposition in the human respiratory tract. Results showed that the pulmonary airway deposition fraction was the largest. It was also found that particles produced from olive oil led to the highest deposition. We strongly recommend minimizing the moisture content of ingredients before cooking and giving priority to the use of peanut oil instead of olive oil to reduce human exposure to PM.

An innovative tool for cost control under fragmented scenarios: The container freight index microinsurance.

With the impact of the COVID-19 pandemic, global container freights have increased dramatically since the second half of 2020, which has significantly hampered the booking activities of fragmented transportation space for small and medium-sized import and export enterprises (SMIEEs). To provide SMIEEs with an effective tool for controlling shipping costs, we propose the design principles of index microinsurance under fragmented scenarios and design the container freight index microinsurance (CFIM) based on a comprehensive analysis of the term, compensation and share structures. We further establish the pricing model for the CFIM and selection procedure for product optimization, and illustrate the framework with a case study based on the data of the China Containerized Freight Index Europe Service, which demonstrates the good performance of the designed product even under extreme market conditions. The design principles proposed can shed light on the innovation of index microinsurance product that meets fragmented needs and the newly designed CFIM, along with the pricing and optimization procedure, provides practitioners with useful tools for cost control.

Long noncoding RNA HITT coordinates with RGS2 to inhibit PD-L1 translation in T cell immunity.

Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein frequently expressed in human cancers that contributes to immune evasion through its binding to PD-1 on activated T cells. Unveiling the mechanisms underlying PD-L1 expression is essential for understanding the impact of the immunosuppressive microenvironment and is also crucial for the purpose of reboosting antitumor immunity. However, how PD-L1 is regulated, particularly at translational levels, remains largely unknown. Here, we discovered that a long noncoding RNA (lncRNA), HIF-1α inhibitor at translation level (HITT), was transactivated by E2F transcription factor 1 (E2F1) under IFN-γ stimulation. It coordinated with regulator of G protein signaling 2 (RGS2) in binding to the 5' UTR of PD-L1, resulting in reduced PD-L1 translation. HITT expression enhanced T cell-mediated cytotoxicity both in vitro and in vivo in a PD-L1-dependent manner. The clinical correlation between HITT/PD-L1 and RGS2/PD-L1 expression was also detected in breast cancer tissues. Together, these findings demonstrate the role of HITT in antitumor T cell immunity, highlighting activation of HITT as a potential therapeutic strategy for enhancing cancer immunotherapy.

Quasi-perfect vortices generated by Pancharatnam-Berry phase metasurfaces for optical spanners and OAM communication.

Optical vortex (OV) can be used in the fields of optical manipulation and optical communication because of its inherent orbital angular momentum (OAM). The size of the OV ring increases with the correlated topological charge (TC), making the OV with large TC not suitable for optical rotation and short-distance communication. Perfect vortex (PV) has attracted much attention due to that its optical transmission profile is almost independent of TC. In this manuscript, we proposed a method to generate quasi- perfect vortices (Q-PVs) by Pancharatnam-Berry (PB) phase metasurfaces, the so-called Q-PV can be regarded as an annularly focused optical vortex whose focal ring in the focal plane has an angular phase gradient. It has a similar property to PV in that its light profile hardly changes with TC in the focal plane. We demonstrated that the Q-PV can be used for optical spanners that particles are trapped and rotated on the specific orbit. Non-coaxial and coaxial Q-PV arrays were further generated for OAM communication applications. We believe that the proposed Q-PVs has potential applications in optical manipulation and optical communication.

Characterization of particulate matter and its extinction ability during different seasons and weather conditions in Sinkiang, China: two case studies.

The Sinkiang Uygur Autonomous Region is located in western China and the centre of the Asian-European continent, which frequently suffers from sandstorm disasters and haze weathers. A 1-year measurement campaign in two selected points in Shihezi and Urumqi of Sinkiang was conducted to characterise the effects of particle matters and factors on particle extinction under different weather conditions. Results showed that the average concentration of PM1-2.5 was 19.83, 9.230, 28.93 and 122.4 µg/m3 in Shihezi and 67.25, 16.80, 59.19 and 324.0 µg/m3 in Urumqi for spring, summer, autumn and winter, respectively. PM5-10 concentrations can reach up to 500.0 and 160.0 µg/m3 during polluted weather conditions in Shihezi and Urumqi, respectively. PM5-10 also accounted for the largest fraction in Shihezi and Urumqi for all types of weather, reaching up to 40.0% under dusty weather conditions. PM1-2.5 significantly increased during winter possibly due to the increased demand for heating compared with non-heating periods. PM0.5-1 is possibly produced from motor vehicle exhaust. Particle size is concluded to be the dominant factor for particle extinction capability under fine weather based on calculations of aerosol optical properties. The refractive index for a particle with a diameter of 100 µm (3.10-3.11i) is substantially larger than that with a diameter of 0.5000 µm (1.600-0.07000i), but the extinction capability of the latter is 1.30 times that of the former. Comparatively, when the mass concentration of coarse particles is over 17.0 times that of the fine particles, and then mass concentration becomes the dominant factor. Therefore, visibility is negatively correlated to particle mass variations during dust storms and hazy days but not for fine days.

Characterizing pollutant emissions from mosquito repellents incenses and implications in risk assessment of human health.

Mosquito-repellent incense is one of the most popular products used for dispelling mosquitos during summer in China. It releases large amounts of particulate and gaseous pollutants which constitute a potential hazard to human health. We conducted chamber experiment to characterize major pollutants from three types of mosquito-repellent incenses, further assessed the size-fractionated deposition in human respiratory system, and evaluated the indoor removing efficiency by fresh air. Results showed that the released pollutant concentrations were greater than permissible levels in regulations in GB3095-2012, as well as suggested by the World Health Organization (WHO). Formaldehyde accounted for 10-20% of the total amount of pollutants. Fine particles dominated in the total particulate concentrations. Geometric standard deviation (GSD) of particle number size distributions was in the range of 1.45-1.93. Count median diameter (CMD) ranged from 100 to 500 nm. Emission rates, burning rates and emission factors of both particulate and gaseous pollutants were compared and discussed. The deposition fractions in pulmonary airway from the disc solid types reached up to 52.7% of the total deposition, and the largest deposition appeared on juvenile group. Computational Fluid Dynamics (CFD) modellings indicated air-conditioner on and windows closed was the worst case. The highest concentration was 180-200 times over the standard limit.

Emissions of volatile organic compounds (VOCs) from cooking and their speciation: A case study for Shanghai with implications for China.

Cooking emission is one of sources for ambient volatile organic compounds (VOCs), which is deleterious to air quality, climate and human health. These emissions are especially of great interest in large cities of East and Southeast Asia. We conducted a case study in which VOC emissions from kitchen extraction stacks have been sampled in total 57 times in the Megacity Shanghai. To obtain representative data, we sampled VOC emissions from kitchens, including restaurants of seven common cuisine types, canteens, and family kitchens. VOC species profiles and their chemical reactivities have been determined. The results showed that 51.26%±23.87% of alkane and 24.33±11.69% of oxygenated VOCs (O-VOCs) dominate the VOC cooking emissions. Yet, the VOCs with the largest ozone formation potential (OFP) and secondary organic aerosol potential (SOAP) were from the alkene and aromatic categories, accounting for 6.8-97.0% and 73.8-98.0%, respectively. Barbequing has the most potential of harming people's heath due to its significant higher emissions of acetaldehyde, hexanal, and acrolein. Methodologies for calculating VOC emission factors (EF) for restaurants that take into account VOCs emitted per person (EFperson), per kitchen stove (EFkitchen stove) and per hour (EFhour) are developed and discussed. Methodologies for deriving VOC emission inventories (S) from restaurants are further defined and discussed based on two categories: cuisine types (Stype) and restaurant scales (Sscale). The range of Stype and Sscale are 4124.33-7818.04t/year and 1355.11-2402.21t/year, respectively. We also found that Stype and Sscale for 100,000 people are 17.07-32.36t/year and 5.61-9.95t/year, respectively. Based on Environmental Kuznets Curve, the annual total amount of VOCs emissions from catering industry in different provinces in China was estimated, which was 5680.53t/year, 6122.43t/year, and 66,244.59t/year for Shangdong and Guangdong provinces and whole China, respectively. Large and medium-scaled restaurants should be paid more attention with respect to regulation of VOCs.

Role of Chinese cooking emissions on ambient air quality and human health.

Chinese-style cooking often involves volatilization of oils which can potentially produce a large number of pollutants, which have adverse impact on environment and human health. Therefore, we have reviewed 75 published studies associated with research topic among Mainland China, Hong Kong and Taiwan, involving studies on the roles of food ingredients and oil type, cooking style impacting on generated pollutants, and human health. The highest concentration occurred including: 1) when peat, wood, and raw coal were used in stoves; 2) olive oil was adopted; 3) cooking with high temperatures; and 4) without cleaning technology. We conclude that PM concentrations for cooking emissions were between 0.14 and 24.46mg/cm3. VOC concentrations varied from 0.35 to 3.41mg/m3. Barbeque produced the greatest mass concentrations compared to Sichuan cuisine, canteen and other restaurants. The PAHs concentration emitted from the exhaust stacks, dining area and kitchen ranged from 0.0175µg/m3 to 83µg/m3. The largest amount of gaseous pollutants emitted was recorded during incomplete combustion of fuel or when a low combustion efficiency (CO2/ (CO+CO2)<0.5) was observed. The variation range was 6.27-228.89mg/m3, 0.16-0.80mg/m3, 0.69-4.33mg/m3, 0.70-21.70mg/m3 for CO, CO2, NO2 and SO2 respectively. In regards to the toxicity and exposure, current findings concluded that both the dose and exposure time are significant factors to be considered. Scientific research in this area has been mainly driven by comparison among emissions from various ingredients and cooking techniques. There is still a need for more comprehensive studies to fully characterise the cooking emissions including their physical and chemical transformations which is crucial for accurate estimation of their impacts on the environment and human health.