Nonlinear country-heterogenous impact of the Indian Ocean Dipole on global economies.

A positive Indian Ocean Dipole features an anomalously high west-minus-east sea surface temperature gradient along the equatorial Indian Ocean, affecting global extreme weathers. Whether the associated impact spills over to global economies is unknown. Here, we develop a nonlinear and country-heterogenous econometric model, and find that a typical positive event causes a global economic loss that increases for further two years after an initial shock, inducing a global loss of hundreds of billion US dollars, disproportionally greater to the developing and emerging economies. The loss from the 2019 positive event amounted to US$558B, or 0.67% in global economic growth. Benefit from a negative dipole event is far smaller. Under a high-emission scenario, a projected intensification in Dipole amplitude causes a median additional loss of US$5.6 T at a 3% discount rate, but likely as large as US$24.5 T. The additional loss decreases by 64% under the target of the Paris Agreement.

The combined use of B vitamins and probiotics promotes B vitamin absorption and increases Akkermansia abundance.

B vitamins and probiotics are commonly used dietary supplements with well-documented health benefits. However, their potential interactions remain poorly understood. This study aims to explore the effects and underlying mechanisms of the combined use of B vitamins and probiotics by liquid chromatography-triple quadrupole mass spectrometry analysis, pharmacokinetic modeling, and 16S rRNA gene sequencing. By intragastric administration of seven B vitamins and three Lactobacillus strains to healthy rats (n = 8 per group), we found that probiotics significantly promoted the absorption (by approximately 14.5% to 71.2%) of vitamins B1, B3, B5, and B12. By conducting in vitro experiments (n = 3 per group) and a pseudo-germ-free rat model-based pharmacokinetic study (n = 6 per group), we confirmed that probiotics primarily enhanced the B vitamin absorption through gut microbiota-mediated mechanisms, rather than by directly producing B vitamins. Furthermore, we evaluated the effects of B vitamins and probiotics on the colon and gut microbiota by treating the pseudo-germ-free rats with blank solution, B vitamins, probiotics, and B vitamins + probiotics (n = 5 per group), respectively. Histopathological examination showed that the combination of B vitamins and probiotics synergistically alleviated the rat colon damage. High-throughput genetic sequencing also revealed the synergistic effect of B vitamins and probiotics in modulating the gut microbiota, particularly increasing the abundance of Verrucomicrobia and Akkermansia. In summary, the combined administration of B vitamins and probiotics may have a higher efficacy than using them alone.

Cyclophosphamide activates ferroptosis-induced dysfunction of Leydig cells via SMAD2 pathway†.

Cyclophosphamide (CP) is a widely used chemotherapeutic drug and immunosuppressant in the clinic, and the hypoandrogenism caused by CP is receiving more attention. Some studies found that ferroptosis is a new mechanism of cell death closely related to chemotherapeutic drugs and plays a key role in regulating reproductive injuries. The purpose of this study is to explore ferroptosis' role in testicular Leydig cell dysfunction and molecular mechanisms relating to it. In this study, the level of ferroptosis in the mouse model of testicular Leydig cell dysfunction induced by CP was significantly increased and further affected testosterone synthesis. The ferroptosis inhibitors ferrostatin-1 (Fer-1) and iron chelator deferoxamine (DFO) can improve injury induced by CP. The results of immunohistochemistry showed that Fer-1 and DFO could improve the structural disorder of seminiferous tubules and the decrease of the number of Leydig cells in testicular tissue induced by CP. Immunofluorescence and western blot confirmed that Fer-1 and DFO could improve the expression of key enzymes in testosterone synthesis. The activation of SMAD family member 2 (Smad2)/cyclin-dependent kinase inhibitor 1A (Cdkn1a) pathway can improve the ferroptosis of Leydig cells induced by CP and protect the function of Leydig cells. By inhibiting the Smad2/Cdkn1a signal pathway, CP can regulate ferroptosis, resulting in testicular Leydig cell dysfunction. In this study, CP-induced hypoandrogenism is explained theoretically and a potential therapeutic strategy is provided.

Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment.

The brain and gut are intricately connected and respond to various stimuli. Stress-induced brain-gut communication is implicated in the pathogenesis and relapse of gut disorders. The mechanism that relays psychological stress to the intestinal epithelium, resulting in maladaptation, remains poorly understood. Here, we describe a stress-responsive brain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment. Psychological stress-triggered sympathetic output enriches gut commensal Lactobacillus murinus, increasing the production of indole-3-acetate (IAA), which contributes to a transferrable loss of intestinal secretory cells. Bacterial IAA disrupts ISC mitochondrial bioenergetics and thereby prevents secretory lineage commitment in a cell-intrinsic manner. Oral α-ketoglutarate supplementation bolsters ISC differentiation and confers resilience to stress-triggered intestinal epithelial injury. We confirm that fecal IAA is higher in patients with mental distress and is correlated with gut dysfunction. These findings uncover a microbe-mediated brain-gut pathway that could be therapeutically targeted for stress-driven gut-brain comorbidities.

Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.

Nonlinear El Niño impacts on the global economy under climate change.

The El Niño-Southern Oscillation (ENSO) is a consequential climate phenomenon affecting global extreme weather events often with largescale socioeconomic impacts. To what extent the impact affects the macroeconomy, how long the impact lasts, and how the impact may change in a warming climate are important questions for the field. Using a smooth nonlinear climate-economy model fitted with historical data, here we find a damaging impact from an El Niño which increases for a further three years after initial shock, amounting to multi-trillion US dollars in economic loss; we attribute a loss of US$2.1 T and US$3.9 T globally to the 1997-98 and 2015-16 extreme El Niño events, far greater than that based on tangible losses. We find impacts from La Niña are asymmetric and weaker, and estimate a gain of only US$0.06 T from the 1998-99 extreme La Niña event. Under climate change, economic loss grows exponentially with increased ENSO variability. Under a high-emission scenario, increased ENSO variability causes an additional median loss of US$33 T to the global economy at a 3% discount rate aggregated over the remainder of the 21st century. Thus, exacerbated economic damage from changing ENSO in a warming climate should be considered in assessments of mitigation strategies.

Association between hospitalizations for asthma exacerbation and weather conditions in Qingdao: an ecological study.

Background: The hospitalization for asthma exacerbation has varied with seasons, however, the underlying weather reasons have not been fully explored yet. This study is aimed to explore the effect of weather factors on increased number of hospitalization due to worsening of asthma symptoms. This will provide more information to the relevant authorities to allocate appropriate medical resources as per the weather conditions in Qingdao, China. Methods: All adult patients admitted for asthma exacerbation from 1 January, 2017 to 31 December, 2019 were enrolled from 13 main hospitals of Qingdao. The clinical data, including age, sex, smoking history, etc., were collected from the electronic medical record (EMR) systems. The hourly air quality of Qingdao from 2017-2019, including the air quality index (AQI), PM2.5 and PM10, was obtained from the China National Environmental Monitoring Centre. All these parameters during 2017-2019 were compared monthly. For meteorological data, the monthly horizontal wind at 850 hPa and vertical velocity at 500 hPa during 1960-2020 were obtained from National Center for Environmental Prediction (NCEP) and the National Center for Atmospheric Research (NCAR) global reanalysis dataset. The correlation analysis was applied to determine the association between asthma hospitalizations and the environmental factors, including atmospheric pressure, humidity, vertical visibility, and etc., monthly. Results: In all, 10,549 asthmatic inpatients (45.7% males, 54.3% females) were included in the study. The inpatients number for asthma exacerbation had a plateau lasting from March to June of 2019, accompanied with high PM2.5 and PM10, as well as bad air quality from January to March of 2019, potentially governed by the El Niño event in 2018. However, there was no significance correlation between the number of asthma hospitalizations and the average value of all environmental factors. Conclusions: The high rate of hospitalization for asthma exacerbation in Qingdao during the spring of 2019 was associated with the unfavorable weather conditions, which might be linked to the atmospheric circulation in East Asia.

Experimental Study on the Unsteady Spray Combustion Process of a Liquid Oxygen/Methane Swirl Coaxial Injector.

The present study experimentally investigated the dynamic spray combustion process of a liquid-centered swirl coaxial injector using liquid oxygen/methane in an optically accessible liquid rocket engine. Data were obtained at combustor pressures from 0.4 to 1.8 MPa and the ratio of the oxidizer mass flow rate to the fuel rate between 1.32 and 1.55. Liquid oxygen was injected at 120 K, and the injection temperature of gaseous methane was about 285 K. Based on the obtained spatial distribution and oscillation characteristics of liquid oxygen/methane flame, the combustion process was described by four subprocesses: ignition, low-frequency oscillation combustion, quasi-steady state combustion, and shutdown. In the quasi-steady state combustion subprocess, both the flame length and the normalized flame area are the largest, and the flame expansion angle is the smallest. At the initial stage of combustion, the instability of the liquid oxygen phase state leads to flame instability, which generates low-frequency unstable combustion with a dominant frequency of 93.74 Hz. In addition, the high-frequency (2500-3000 Hz) oscillation of the flame appeared in the whole combustion process. It has been confirmed to be caused by the self-pulsation of spray. Furthermore, with the increase in liquid oxygen manifold pressure, the liquid oxygen phase state changes from a two-phase mixture of liquid and gaseous oxygen to a liquid phase, which increases the mass flow rate of liquid oxygen entering into the combustor, thus generating the increase in the high oscillation frequency of the flame through the whole combustion process.

Interaction between retinoic acid and FGF/ERK signals are involved in Dexamethasone-induced abnormal myogenesis during embryonic development.

Despite the common application in pregnancy at clinical practice, it remains ambiguous whether dexamethasone (Dex) exposure can affect embryonic myogenesis. In this study, firstly we showed that 10-6 M Dex (Cheng et al., 2016; 2017) treatment resulted in abnormal myogenesis in chicken embryos. Secondly, we demonstrated that 10-6 M Dex-induced abnormality of myogenesis resulted from aberrant cell proliferation, as well as from alteration of the differentiation process from the early stage of somitogenesis up to the late stage of myogenesis. The above-mentioned results caused by Dex exposure might be due to the aberrant gene expressions of somite formation (Raldh2, Fgf8, Wnt3a, ß-catenin, Slug, Paraxis, N-cadherin) and differentiation (Pax3, MyoD, Wnt3a, Msx1, Shh). Thirdly, RNA sequencing implied the statistically significant differential gene expressions in regulating the myofibril and systemic development, as well as a dramatical alteration of retinoic acid (RA) signaling during somite development in the chicken embryos exposed to Dex. The subsequent validation experiments verified that Dex treatment indeed led to a metabolic change of RA signaling, which was up-regulated and principally mediated by FGF-ERK signaling revealed by means of the combination of chicken embryos and in vitro C2C12 cells. These findings highlight that 10-6 M Dex exposure enhances the risk of abnormal myogenesis through interfering with RA signaling during development.

Pilot study on long-term simulation of PCB-153 human body burden in the Tibetan Plateau.

The historical body burden of 2,2',4,4',5,5'-Hexachlorobiphenyl (PCB-153) in the Tibet Autonomous Region (TAR) population was simulated on the basis of localized exposure factors and dietary data, which present a preliminary attempt to quantify the influence of high lipid dietary patterns, grain transported from inland China, and atmospheric transport on human exposure to polychlorinated biphenyls (PCBs). Herdsman with large animal-based food consumption exhibited the highest body burden that was comparable with that in inland China. The body burden of other residents was within the range of low-to-moderate level. High-lipid diet of urban residents caused their body burden being 1.5--2.5 times higher than that of rural residents. The consumption of grain transported from higher polluted areas can also result in 50%-115% increase in the body burden of Tibetan rural residents compared with when local produced grain is consumed, suggesting that the influence of grain logistic can be as important as dietary patterns. The exposure risk for rural residents associated with grain logistic should not be ignored even if they consumed less high-lipid food. By splitting the inventory, over 80% of the PCB-153 pollution in the TAR was identified to be induced by atmospheric transport from foreign countries. However, the grain logistic contributed approximately half of the overall human body burden of Tibetan residents recently if assuming that the grain shortage was supplied by adjacent Sichuan Province. The combined influence of high-lipid diet, atmospheric transport and food logistic highlights the difficulties of risk control in remote regions that accumulate POPs, such as TAR.

Dysbacteriosis-induced LPS elevation disturbs the development of muscle progenitor cells by interfering with retinoic acid signaling.

Whether myogenesis is affected by the maternal gut dysbacteriosis still remains ambiguous. In this study, first we show the elevated level of lipopolysaccharides (LPS) in a gut microbiota dysbiosis mouse model. Second, we demonstrate that the diameter of muscle fibers, limb development, and somitogenesis were inhibited in both the gut microbiota dysbiosis and LPS exposed mice and chicken embryos. These might be due to LPS disturbed the cell survival and key genes which regulate the somitogenesis and myogenesis. RNA sequencing and subsequent validation experiments verified that retinoic acid (RA) signaling perturbation was mainly responsible for the aberrant somite formation and differentiation. Subsequently, we found that LPS-induced reactive oxygen species (ROS generation and antioxidant genes such as Nrf2, AKR1B10) contributed to the above -mentioned interference with RA signaling. These findings highlight that the gut microbiota homeostasis is also involved in regulating the development of muscle progenitor cells during pregnancy.

Realism of modelled Indian summer monsoon correlation with the tropical Indo-Pacific affects projected monsoon changes.

El Niño-Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD) tend to exert an offsetting impact on Indian summer monsoon rainfall (ISMR), with an El Niño event tending to lower, whereas a positive IOD tending to increase ISMR. Simulation of these relationships in Phase Five of the Coupled Model Intercomparison Project has not been fully assessed, nor is their impact on the response of ISMR to greenhouse warming. Here we show that the majority of models simulate an unrealistic present-day IOD-ISMR correlation due to an overly strong control by ENSO. As such, a positive IOD is associated with an ISMR reduction in the simulated present-day climate. This unrealistic present-day correlation is relevant to future ISMR projection, inducing an underestimation in the projected ISMR increase. Thus uncertainties in ISMR projection can be in part induced by present-day simulation of ENSO, the IOD, their relationship and their rainfall correlations.

Dynamics of changing impacts of tropical Indo-Pacific variability on Indian and Australian rainfall.

A positive Indian Ocean Dipole (IOD) and a warm phase of the El Niño-Southern Oscillation (ENSO) reduce rainfall over the Indian subcontinent and southern Australia. However, since the 1980s, El Niño's influence has been decreasing, accompanied by a strengthening in the IOD's influence on southern Australia but a reversal in the IOD's influence on the Indian subcontinent. The dynamics are not fully understood. Here we show that a post-1980 weakening in the ENSO-IOD coherence plays a key role. During the pre-1980 high coherence, ENSO drives both the IOD and regional rainfall, and the IOD's influence cannot manifest itself. During the post-1980 weak coherence, a positive IOD leads to increased Indian rainfall, offsetting the impact from El Niño. Likewise, the post-1980 weak ENSO-IOD coherence means that El Niño's pathway for influencing southern Australia cannot fully operate, and as positive IOD becomes more independent and more frequent during this period, its influence on southern Australia rainfall strengthens. There is no evidence to support that greenhouse warming plays a part in these decadal fluctuations.