Precipitation regime changes in High Mountain Asia driven by cleaner air.

High Mountain Asia (HMA) has experienced a spatial imbalance in water resources in recent decades, partly because of a dipolar pattern of precipitation changes known as South Drying-North Wetting1. These changes can be influenced by both human activities and internal climate variability2,3. Although climate projections indicate a future widespread wetting trend over HMA1,4, the timing and mechanism of the transition from a dipolar to a monopolar pattern remain unknown. Here we demonstrate that the observed dipolar precipitation change in HMA during summer is primarily driven by westerly- and monsoon-associated precipitation patterns. The weakening of the Asian westerly jet, caused by the uneven emission of anthropogenic aerosols, favoured a dipolar precipitation trend from 1951 to 2020. Moreover, the phase transition of the Interdecadal Pacific Oscillation induces an out-of-phase precipitation change between the core region of the South Asian monsoon and southeastern HMA. Under medium- or high-emission scenarios, corresponding to a global warming of 0.6-1.1 °C compared with the present, the dipolar pattern is projected to shift to a monopolar wetting trend in the 2040s. This shift in precipitation patterns is mainly attributed to the intensified jet stream resulting from reduced emissions of anthropogenic aerosols. These findings underscore the importance of considering the impact of aerosol emission reduction in future social planning by policymakers.

Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non-small cell lung cancer.

In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resistant to most currently approved EGFR inhibitors. This report describes the structure-guided design of a novel series of potent, irreversible inhibitors of EGFR exon 20 insertion mutations, including the V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led to the discovery of mobocertinib (compound 21c), which inhibited growth of Ba/F3 cells expressing the ASV insertion with a half-maximal inhibitory concentration of 11 nM and with selectivity over wild-type EGFR. Daily oral administration of mobocertinib induced tumor regression in a Ba/F3 ASV xenograft mouse model at well-tolerated doses. Mobocertinib was approved in September 2021 for the treatment of adult patients with advanced NSCLC with EGFR exon 20 insertion mutations with progression on or after platinum-based chemotherapy.

Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.

BACKGROUND: Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM). METHODS: The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib. RESULTS: Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months. CONCLUSIONS: Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.

Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples.

Three sets of polymerase chain reaction (PCR) primers were designed for heminested PCR amplification of the target DNA fragments in the human genome which include the site of BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del respectively, to prepare the templates for direct Sanger sequencing screen of these three founder mutations. With a robust PCR mixture, crude proteinase K digestate of the fixed cervicovaginal cells in the liquid-based Papanicolaou (Pap) cytology specimens can be used as the sample for target DNA amplification without pre-PCR DNA extraction, purification and quantitation. The post-PCR products can be used directly as the sequencing templates without further purification or quantitation. By simplifying the frontend procedures for template preparation, the cost for screening these three founder mutations can be reduced to about US $200 per test when performed in conjunction with human papillomavirus (HPV) assays now routinely ordered for cervical cancer prevention. With this projected price structure, selective patients in a high-risk population can be tested and each provided with a set of DNA sequencing electropherograms to document the absence or presence of these founder mutations in her genome to help assess inherited susceptibility to breast and ovarian cancer in this era of precision molecular personalized medicine.

Vitamin D deficiency and the risk of anemia: a meta-analysis of observational studies.

AIMS: Anemia and vitamin D deficiency (VDD) are both very important health issues, recent accumulating evidence shows that VDD is prevalent in individuals with anemia. This meta-analysis aimed to detect a relationship between VDD and anemia. METHODS: We identified eligible studies by searching the Pub Med, Embase and Cochrane Library before October 2014. Quality assessments were performed with the Newcastle-Ottawa Scale. Heterogeneity was evaluated by Cochran's Q test and source of heterogeneity was detected by subgroup analysis and sensitivity analysis. RESULTS: A total of seven studies involving 5183 participants were included in the meta-analysis. VDD was associated with an increased incidence of anemia (OR = 2.25, 95% CI = 1.47-3.44), with significant evidence of heterogeneity among these studies (p for heterogeneity < 0.001, I(2) = 84.0%). The subgroup and sensitivity analysis confirmed the stability of the results and no publication bias was detected. CONCLUSION: Our outcomes showed that VDD increased the risk of developing anemia. More researches are warranted to clarify an understanding of the association between VDD and risk of anemia.

Study on Fatigue Life of Aluminum Alloy 6061-T6 Based on Random Defect Characteristics.

A certain number of hole-like defects will occur in aluminum alloys under cyclic loading. The internal holes will reduce the strength of the material and cause stress concentration, which will aggravate the development of fatigue damage. A classification method of defect features based on X-ray CT damage data is proposed. The random hole distribution model is established through the linear congruence method and the region division method. The hole parameter is introduced as the intermediate variable of the 3D reconstruction model of internal defects. In the mesoscopic stage, the function relationship between the distribution of random holes and the fatigue life is established based on the coupling relationship between the number and proportion of pores and the fatigue life. In the macroscopic stage, the relationship between the random holes and the macroscopic crack growth life is established by taking the crack length as the damage variable. The crack propagation rate decreased with the increase in the number of holes. The prediction model of the whole life stage is established using the life function from microcrack initiation to macroscopic crack propagation. Finally, the validity of the whole stage fatigue life prediction model is demonstrated through the comparison and verification of experiments, which provides a certain engineering value for the life estimation of 6061-T6 aluminum alloy materials.

Design of Cellulose Nanocrystal-Based Self-Healing Nanocomposite Hydrogels and Application in Motion Sensing and Sweat Detection.

Hydrogels, as flexible materials, have been widely used in the field of flexible sensors. Human sweat contains a variety of biomarkers that can reflect the physiological state of the human body. Therefore, it is of great practical significance and application value to realize the detection of sweat composition and combine it with human motion sensing through a hydrogel. Based on mussel-inspired chemistry, polydopamine (PDA) and gold nanoparticles (AuNPs) were coated on the surface of cellulose nanocrystals (CNCs) to obtain CNC-based nanocomposites (CNCs@PDA-Au), which could simultaneously enhance the mechanical, electrochemical, and self-healing properties of hydrogels. The CNCs@PDA-Au was composited with poly(vinyl alcohol) (PVA) hydrogel to obtain the nanocomposite hydrogel (PVA/CNCs@PDA-Au) by freeze-thaw cycles. The PVA/CNCs@PDA-Au has excellent mechanical strength (7.2 MPa) and self-healing properties (88.3%). The motion sensors designed with PVA/CNCs@PDA-Au exhibited a fast response time (122.9 ms), wide strain sensing range (0-600.0%), excellent stability, and fatigue resistance. With the unique electrochemical redox properties of uric acid, the designed hydrogel sensor successfully realized the detection of uric acid in sweat with a wide detection range (1.0-100.0 µmol/L) and low detection limit (0.42 µmol/L). In this study, the dual detection of human motion and uric acid in sweat was successfully realized by the designed PVA/CNCs@PDA-Au nanocomposite hydrogel.

Enhanced risk of record-breaking regional temperatures during the 2023-24 El Niño.

In 2023, the development of El Niño is poised to drive a global upsurge in surface air temperatures (SAT), potentially resulting in unprecedented warming worldwide. Nevertheless, the regional patterns of SAT anomalies remain diverse, obscuring where historical warming records may be surpassed in the forthcoming year. Our study underscores the significant influence of El Niño and the persistence of climate signals on the inter-annual variability of regional SAT, both in amplitude and spatial distribution. The likelihood of global mean SAT exceeding historical records, calculated from July 2023 to June 2024, is estimated at 90%, contingent upon annual-mean sea surface temperature anomalies in the eastern equatorial Pacific exceeding 0.6 °C. Regions particularly susceptible to recording record-high SAT include coastal and adjacent areas in Asia such as the Bay of Bengal and the South China Sea, as well as Alaska, the Caribbean Sea, and the Amazon. This impending warmth heightens the risk of year-round marine heatwaves and escalates the threat of wildfires and other negative consequences in Alaska and the Amazon basin, necessitating strategic mitigation measures to minimize potential worst-case impacts.

Present situation and development prospects of the diagnosis and treatment of rotator cuff tears.

Rotator cuff tears are an important cause of shoulder pain and are caused by degeneration or trauma of the shoulder tendon at the anatomical neck of the humeral head. The understanding and research of rotator cuff tears have a history of hundreds of years, and their etiology, diagnosis, and treatment have a complete system, but some detailed rules of diagnosis and treatment still have room for development. This research paper briefly introduces the diagnosis and treatment of rotator cuff tears. The current situation and its valuable research direction are described.

Robust projection of East Asian summer monsoon rainfall based on dynamical modes of variability.

The Asian monsoon provides the freshwater that a large population in Asia depends on, but how anthropogenic climate warming may alter this key water source remains unclear. This is partly due to the prevailing point-wise assessment of climate projections, even though climate change patterns are inherently organized by dynamics intrinsic to the climate system. Here, we assess the future changes in the East Asian summer monsoon precipitation by projecting the precipitation from several large ensemble simulations and CMIP6 simulations onto the two leading dynamical modes of internal variability. The result shows a remarkable agreement among the ensembles on the increasing trends and the increasing daily variability in both dynamical modes, with the projection pattern emerging as early as the late 2030 s. The increase of the daily variability of the modes heralds more monsoon-related hydrological extremes over some identifiable East Asian regions in the coming decades.

Constrained future brightening of solar radiation and its implication for China's solar power.

As Earth's primary energy source, surface downward solar radiation (R s) determines the solar power potential and usage for climate change mitigation. Future projections of R s based on climate models have large uncertainties that interfere with the efficient deployment of solar energy to achieve China's carbon-neutrality goal. Here we assess 24 models in the latest Coupled Model Intercomparison Project Phase 6 with historical observations in China and find systematic biases in simulating historical R s values likely due to model biases in cloud cover and clear-sky radiation, resulting in largely uncertain projections for future changes in R s. Based on emergent constraints, we obtain credible R s with narrowed uncertainties by ∼56% in the mid-twenty-first century and show that the mean R s change during 2050-2069 relative to 1995-2014 is 30% more brightening than the raw projections. Particularly in North China and Southeast China with higher power demand, the constrained projections present more significant brightening, highlighting the importance of considering the spatial changes in future Rs when locating new solar energy infrastructures.

Middle east warming in spring enhances summer rainfall over Pakistan.

The edge of a monsoon region is usually highly sensitive to climate change. Pakistan, which is located on the northern edge of the Indian monsoon, is highly vulnerable to heavy rainfall and has witnessed several debilitating floods exacerbated by global warming in recent years. However, the mechanisms for the frequent Pakistan floods are yet not fully understood. Here, we show that the Middle East is undergoing an increase in land heating during spring, which is responsible for 46% of the intensified rainfall over Pakistan and northwestern India during 1979-2022. This springtime land warming causes a decline in sea level pressure (SLP), which strengthens the meridional SLP gradient between the Middle East and the southern Arabian Sea and drives the changes of low-level jet (LLJ) subsequently. The impact persists into summer and results in a northward shift of the monsoonal LLJ, accompanied by strong positive vorticity in the atmosphere and enhanced moisture supply to Pakistan. Consequently, the transition region between the summer monsoon in South Asia and the desert climate in West Asia is shifted northwestward, posing significantly enhanced risk of floods over Pakistan and northwestern India.

Increased impact of heat domes on 2021-like heat extremes in North America under global warming.

During summer 2021, Western North America (WNA) experienced an unprecedented heatwave with record-breaking high temperatures associated with a strong anomalous high-pressure system, i.e., a heat dome. Here, we use a flow analog method and find that the heat dome over the WNA can explain half of the magnitude of the anomalous temperature. The intensities of hot extremes associated with similar heat dome-like atmospheric circulations increase faster than background global warming in both historical change and future projection. Such relationship between hot extremes and mean temperature can be partly explained by soil moisture-atmosphere feedback. The probability of 2021-like heat extremes is projected to increase due to the background warming, the enhanced soil moisture-atmosphere feedback and the weak but still significantly increased probability of the heat dome-like circulation. The population exposure to such heat extremes will also increase. Limiting global warming to 1.5 °C instead of 2 °C (3 °C) would lead to an avoided impact of 53% (89%) of the increase in population exposure to 2021-like heat extremes under the RCP8.5-SSP5 scenario.

Reversed asymmetric warming of sub-diurnal temperature over land during recent decades.

In the latter half of the twentieth century, a significant climate phenomenon "diurnal asymmetric warming" emerged, wherein global land surface temperatures increased more rapidly during the night than during the day. However, recent episodes of global brightening and regional droughts and heatwaves have brought notable alterations to this asymmetric warming trend. Here, we re-evaluate sub-diurnal temperature patterns, revealing a substantial increase in the warming rates of daily maximum temperatures (Tmax), while daily minimum temperatures have remained relatively stable. This shift has resulted in a reversal of the diurnal warming trend, expanding the diurnal temperature range over recent decades. The intensified Tmax warming is attributed to a widespread reduction in cloud cover, which has led to increased solar irradiance at the surface. Our findings underscore the urgent need for enhanced scrutiny of recent temperature trends and their implications for the wider earth system.

East Asian summer monsoon enhanced by COVID-19.

Anthropogenic emissions decreased dramatically during the COVID-19 pandemic, but its possible effect on monsoon is unclear. Based on coupled models participating in the COVID Model Intercomparison Project (COVID-MIP), we show modeling evidence that the East Asian summer monsoon (EASM) is enhanced by 2.2% in terms of precipitation and by 5.4% in terms of the southerly wind at lower troposphere, and the amplitude of the forced response reaches about 1/3 of the standard deviation for interannual variability. The enhanced EASM during COVID-19 pandemic is a fast response to reduced aerosols, which is confirmed by the simulated response to the removal of all anthropogenic aerosols. The observational evidence, i.e., the anomalously strong EASM observed in 2020 and 2021, also supports the simulated enhancement of EASM. The essential mechanism for the enhanced EASM in response to COVID-19 is the enhanced zonal thermal contrast between Asian continent and the western North Pacific in the troposphere, due to the reduced aerosol concentration over Asian continent and the associated latent heating feedback. As the enhancement of EASM is a fast response to the reduction in aerosols, the effect of COVID-19 on EASM dampens soon after the rebound of emissions based on the models participating in COVID-MIP. Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-022-06247-8.

Constraining extreme precipitation projections using past precipitation variability.

Projected changes of future precipitation extremes exhibit substantial uncertainties among climate models, posing grand challenges to climate actions and adaptation planning. Practical methods for narrowing the projection uncertainty remain elusive. Here, using large model ensembles, we show that the uncertainty in projections of future extratropical extreme precipitation is significantly correlated with the model representations of present-day precipitation variability. Models with weaker present-day precipitation variability tend to project larger increases in extreme precipitation occurrences under a given global warming increment. This relationship can be explained statistically using idealized distributions for precipitation. This emergent relationship provides a powerful constraint on future projections of extreme precipitation from observed present-day precipitation variability, which reduces projection uncertainty by 20-40% over extratropical regions. Because of the widespread impacts of extreme precipitation, this has not only provided useful insights into understanding uncertainties in current model projections, but is also expected to bring potential socio-economic benefits in climate change adaptation planning.

Observationally constrained projection of Afro-Asian monsoon precipitation.

The Afro-Asian summer monsoon (AfroASM) sustains billions of people living in many developing countries covering West Africa and Asia, vulnerable to climate change. Future increase in AfroASM precipitation has been projected by current state-of-the-art climate models, but large inter-model spread exists. Here we show that the projection spread is related to present-day interhemispheric thermal contrast (ITC). Based on 30 models from the Coupled Model Intercomparison Project Phase 6, we find models with a larger ITC trend during 1981-2014 tend to project a greater precipitation increase. Since most models overestimate present-day ITC trends, emergent constraint indicates precipitation increase in constrained projection is reduced to 70% of the raw projection, with the largest reduction in West Africa (49%). The land area experiencing significant increases of precipitation (runoff) is 57% (66%) of the raw projection. Smaller increases of precipitation will likely reduce flooding risk, while posing a challenge to future water resources management.

Bone Density May Be a Promising Predictor for Blood Loss during Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty (THA), which is performed mostly in elderly individuals, can result in substantial blood loss and thereby imposes a significant physical burden and risk of blood transfusion. The femoral neck cut and reamed acetabulum are the main sites of intraoperative bleeding. Whether the bone density in that region can be used to predict the amount of blood loss in THA is unknown. METHODS: We retrospectively analyzed adult patients undergoing primary THA in the Department of Orthopedics, Peking Union Medical College Hospital, from January 2018 to January 2020. All these patients underwent primary unilateral THA. Patients had their bone mineral density (BMD) recorded within the week before surgery and were stratified and analyzed for perioperative blood loss. Multivariable regressions were utilized to adjust for differences in demographics and comorbidities among groups. RESULTS: A total of 176 patients were included in the study. Intraoperative blood loss was 280.1 ± 119.56 mL. Pearson correlation analysis showed a significant correlation between blood loss and preoperative bone density of both the femoral greater trochanter (R = 0.245, p = 0.001) and the Ward's triangle (R = 0.181, p = 0.016). Stepwise multiple linear regression showed that preoperative bone density of the greater trochanter (p = 0.015, 95% CI: 0.004-0.049) and sex (p = 0.002) were independent risk factors for THA bleeding. The area under the receiver operating characteristic curve (AUROC) of the greater trochanter and Ward's triangle was 0.593 (95% CI: 0.507-0.678, p = 0.035) and 0.603 (95% CI: 0.519-0.688, p = 0.018), respectively. The cutoff T value on the femoral greater trochanter for predicting higher bleeding was -1.75. CONCLUSIONS: In THA patients, preoperative bone density values of the femoral greater trochanter and sex could be promising independent predictors for bleeding during surgery. Osteoporosis and female patients might have lower blood loss in the THA operation.

Identification of chromosomal instability-associated genes as hepatocellular carcinoma progression-related biomarkers to guide clinical diagnosis, prognosis and therapy.

Hepatocellular carcinoma (HCC) is a type of cancer characterized by high heterogeneity and a complex multistep progression process. Significantly-altered biomarkers for HCC need to be identified. Differentially expressed genes and weighted gene co-expression network analyses were used to identify progression-related biomarkers. LASSO-Cox regression and random forest algorithms were used to construct the progression-related prognosis (PRP) score. Three chromosomal instability-associated genes (KIF20A, TOP2A, and TTK) have been identified as progression-related biomarkers. The robustness of the PRP scores were validated using four independent cohorts. Immune status was observed using the single-sample gene set enrichment analysis (ssGSEA). Comprehensive analysis showed that the patients with high PRP score had wider genomic alterations, more malignant phenotypes, and were in a state of immunosuppression. The diagnostic models constructed via logistic regression based on the three genes showed satisfactory performances in distinguishing HCC from cirrhotic tissues or dysplastic nodules. The nomogram combining PRP scores with clinical factors had a better performance in predicting prognosis than the tumor node metastasis classification (TNM) system. We further confirmed that KIF20A, TOP2A, and TTK were highly expressed in HCC tissues than in cirrhotic tissues. Downregulation of all three genes aggravated chromosomal instabilities in HCC and suppressed HCC cells viability both in vitro and in vivo. Overall, our study highlights the important roles of chromosomal instability-associated genes during the progression of HCC and their potential clinical diagnosis and prognostic value and provides promising new ideas for developing therapeutic strategies to improve the outcomes of HCC patients.

Mitigation of China's carbon neutrality to global warming.

Projecting mitigations of carbon neutrality from individual countries in relation to future global warming is of great importance for depicting national climate responsibility but is poorly quantified. Here, we show that China's carbon neutrality (CNCN) can individually mitigate global warming by 0.48 °C and 0.40 °C, which account for 14% and 9% of the global warming over the long term under the shared socioeconomic pathway (SSP) 3-7.0 and 5-8.5 scenarios, respectively. Further incorporating changes in CH4 and N2O emissions in association with CNCN together will alleviate global warming by 0.21 °C and 0.32 °C for SSP1-2.6 and SSP2-4.5 over the long term, and even by 0.18 °C for SSP2-4.5 over the mid-term, but no significant impacts are shown for all SSPs in the near term. Divergent responses in alleviated warming are seen at regional scales. The results provide a useful reference for the global stocktake, which assesses the collective progress towards the climate goals of the Paris Agreement.