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The Caspian Sea underwent a complex series of transgressive and regressive episodes during the Quaternary, with the North Caspian region particularly sensitive to even minor sea-level fluctuations. Outcrops along the Volga River preserve a valuable depositional record of these changes. The Raigorod site, one of the northernmost sections, provides a key stratigraphic archive for reconstructing regional Quaternary environmental changes, but aspects of its stratigraphy, sedimentary architecture, and geochronology have remained uncertain. In this study, using a multi-proxy approach, combining companion borehole data, biolithostratigraphy, geological mapping, and OSL dating, we refined the regional Quaternary framework and clarified several debated regional stratigraphic boundaries. This multidisciplinary approach permitted us to stratify the entire Quaternary interval of the Raigorod site into a series of regional horizons and subhorizons including the Akchagylian, Apsheronian, Tyurkyanian, Bakunian, Khazarian and Khvalynian. Our results show that the Raigorod site evolved from a nearshore setting during the Akchagylian-Apsheronian transgressive phases in the Early Pleistocene to a fluvial regime during the Tyurkyanian regression at the beginning of the Middle Pleistocene. A subsequent Bakunian transgression re-established marine conditions in the study area. The early Khazarian phase is characterized by alternating transgressive and regressive events. Borehole data confirm that Singilian deposits are embedded within the Khazarian sequence, supporting our earlier regional interpretations. The Singilian phase reflects widespread regression and marshland development at the end of the Middle Pleistocene, around MIS 7-6, although OSL dates suggest a younger MIS 5 age. Upper Khazarian deposits reflect stable floodplain conditions driven by local hydrology rather than global climatic forcing. Finally, the overlying Atelian unit, traditionally used as a regional marker, is reinterpreted as periglacial alluvium rather than subaerial loess deposits formed during a major regression, likely associated with MIS 4-3. Our results highlight the value of integrated stratigraphic approaches for regional correlations, while emphasizing limitations in OSL dating in sedimentary settings with complex hydrological and hydrogeological dynamics.

BACKGROUND:The phase 3 CARES-310 trial showed significant improvements in progression-free survival (primary analysis) and overall survival (interim analysis) with the anti-PD-1 antibody camrelizumab plus the oral vascular endothelial growth factor receptor 2 inhibitor rivoceranib versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma. Here, we present the final analysis of overall survival, and updated data on progression-free survival, secondary efficacy endpoints, and safety. METHODS:This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions. Eligible patients were aged 18 years or older, with unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Participants were randomly assigned (1:1) using a centralised interactive response system to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival, assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drugs. The study is complete and was registered with ClinicalTrials.gov, NCT03764293. FINDINGS:Between June 28, 2019, and March 24, 2021, 543 patients (457 [84%] males; 450 [83%] were Asian) were randomly assigned to receive camrelizumab-rivoceranib (n=272) or sorafenib (n=271). At final analysis on June 14, 2023, the median follow-up was 22·1 months (IQR 11·9-30·3) in the camrelizumab-rivoceranib group and 14·9 months (7·2-28·3) in the sorafenib group. Median overall survival was 23·8 months (95% CI 20·6-27·2) with camrelizumab-rivoceranib and 15·2 months (13·2-18·5) with sorafenib (hazard ratio [HR] 0·64 [95% CI 0·52-0·79]; one-sided p<0·0001). Median progression-free survival was 5·6 months (95% CI 5·5-7·4) with camrelizumab-rivoceranib and 3·7 months (3·1-3·7) with sorafenib (HR 0·54 [0·44-0·67]; one-sided p<0·0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (104 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 42 [16%]), increased aspartate aminotransferase (47 [17%] vs 14 [5%]), and increased alanine aminotransferase (38 [14%] vs eight [3%]). Treatment-related serious adverse events were reported in 69 (25%) of 272 patients in the camrelizumab-rivoceranib group and 18 (7%) of 269 patients in the sorafenib group. Treatment-related deaths occurred in one patient each in the camrelizumab-rivoceranib group (multiple organ dysfunction syndrome) and sorafenib group (respiratory failure and circulatory collapse). INTERPRETATION:At final analysis, camrelizumab plus rivoceranib continued to show clinically meaningful survival improvement compared with sorafenib, with manageable safety. The extended follow-up further confirmed the benefit-to-risk profile of camrelizumab plus rivoceranib, supporting the combination as a new first-line treatment option for unresectable hepatocellular carcinoma. FUNDING:Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics.

The article deals with the effect of combined thermomechanical treatment, including equal-channel angular pressing and subsequent bulk ultrasonic treatment, on the microstructure, mechanical and corrosion properties of pure magnesium and Mg-8.6Zn-1.2Zr alloy. It is found that one cycle of equal channel angular pressing makes it possible to increase the strength of the Mg-8.6Zn-1.2Zr alloy by 10 % up to 330 +/- 5 MPa, but there is a significant increase in the corrosion rate in Ringer's solution. Bulk ultrasonic treatment causes some relaxation of the microstructure, characterized by the growth of recrystallized grains and an increase in the fraction of low- angle boundaries. As a result of this treatment scheme, the high ultimate tensile strength of the material is maintained (310 +/- 5 MPa), the ductility of the material and its corrosion resistance increase significantly. For example, after equal channel angular pressing and ultrasonic treatment, the corrosion rate of the Mg-8.6Zn-1.2Zr alloy decreased to similar to 8.2 +/- 0.4 mm/year which is characteristic of the annealed state. Experiments on pure magnesium show similar results, combined deformation and ultrasonic treatments lead to an increase in the fraction of low-angle boundaries, mechanical properties and corrosion resistance in physiological environment.

The purpose of the article is a mathematical justification of the quantitative values of the main parameters of the progressive income tax scale in Russian conditions, considering social and economic parameters. Based on the methods of regression analysis, the boundary of the non-taxable minimum of income tax is determined as the extremum of the polynomial function of the second degree of savings behavior of the population from income. The non-taxable minimum is determined by considering the median income of 78% of the average per capita income. Within the framework of this stage, cross section data were used for 85 constituent entities of the Russian Federation: the savings rate of the population and the average per capita income of the population. Our modified method of linear transformation, which considers differentiated taxation of income within separate tax intervals, allowed us to determine the income tax rates of the proposed tax scale. It is empirically confirmed that the proposed progressive income tax scale can provide significant social, economic and fiscal effects. The study showed that the proposed progressive scale has the greatest effect on regions with initially low parameters of socio-economic development. The rates of the progressive income tax scale substantiated in the study make it possible to ensure a reduction in the tax burden on low-income groups of the population, an increase in entrepreneurial and savings activity of the middle-income group of the population, and an increase in the role of high-income groups in the formation of the revenue side of the budget.

In our previous works, a new beta-solidifying TiAl alloy of the composition Ti-(43.5-44)Al-6(Nb,Zr,Hf)-(0.1-0.15)B (at%) designated as TNZ gamma-TiAl alloy has been designed. One of the ideas of the alloy was to reduce almost to zero the beta(beta 0) phase content to avoid unfavorable phase transformations during long-term exposure at potential service temperatures, i.e. at T >= 700 degrees C. This was achieved by eliminating Mo and alloying with Zr and Hf, which are nearly neutral or weak beta-stabilizing elements. In this work, additional alloying with 1 at% Ta, which is a weak beta stabilizer, was applied to further enhance the high-temperature capability of the TNZ alloy. Microstructure examination revealed two basic phases in the TNZ-Ta alloy, gamma-TiAl and alpha 2-Ti3Al, but the amount of the metastable beta(beta 0) phase slightly increased compared to that in the TNZ alloy. Upset forging and two-stage heat treatment was applied to transform the cast structure into a refined duplex type structure in the TNZ and TNZ-Ta alloy. Tensile and creep tests as well as oxidation resistance test were carried out for the obtained duplex conditions of the alloys. Doping with Ta led to a significant increase in oxidation resistance at 800 degrees C and a slight improvement in tensile properties, while maintaining similar creep properties. In particular, the mass gain after oxidation for 500 h for the TNZ-Ta alloy was 0.48 mg/cm2 versus 0.7 mg/cm2 for the TNZ alloy. The TNZ and TNZ-Ta alloys with a duplex structure demonstrated clear superiority in creep and oxidation resistance compared to that of the TNM alloy with a near duplex structure without compromising room temperature ductility. The room temperature ductility of the TNZ/TNZ-Ta and TNM alloys was El= 1.3-1.53 % and El= 0.85 %, respectively. The new Ti-44Al-7(Nb,Zr,Hf,Ta)-0.15B alloy can be expectedly used at operating temperatures up to 800 degrees C without coatings or surface treatments to protect against oxidation.