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Unstable hydrological cycles and water resource instability over and around the Tibetan Plateau (TP) are topics of wide concern. The Indian summer monsoon (ISM) is one of the TP’s most important moisture sources; as such, its behavior is key to any changes in precipitation and water-related environments. However, there have been relatively few thorough investigations into ISM activities. Here we primarily explore ISM activities using outgoing longwave radiation (OLR) datasets in TP, and precipitation isotopes recorded at Lhasa, for the period 1975–2020. Our major findings are that 1) the ISM onset (retreat date) is between ∼31 May and 19 July (∼8 August–27 September), with ISM duration of ∼40–110 days; 2) significant spatial inhomogeneous patterns are evident in ISM activities, i.e., the western part of our study area experiences earlier ISM onset, delayed retreat, longer duration, and greater intensity and strength, and the inverse is true in the eastern sector of the study area; 3) the ISM activities that dominate the 1975–98 period determine their general patterns over the entire 1975–2020 period, taking into account evident discrepancies in subperiods; and 4) the negative relations between precipitation δ18O and ISM intensity/strength at Lhasa confirm the ISM activities defined using OLR. These results will improve our understanding of hydrological cycles in TP and provide insights into hydrological studies in the “Asian Water Tower” region. Significance Statement Over the recent decades, the Tibetan Plateau (TP) (Asian Water Tower) has undergone dramatic environmental changes, evinced by the instabilities of hydrological cycles. As one of TP’s most important moisture sources, the Indian summer monsoon (ISM) is key to changes in precipitation and water-related environments. To get thorough investigations into ISM activities, we primarily explore ISM activities using outgoing longwave radiation (OLR) datasets in TP and precipitation isotopes at Lhasa. Significant spatial inhomogeneous patterns are evident in ISM activities: the western part experiences earlier ISM onset, delayed retreat, longer duration, and stronger intensity and strength, and the inverse occurs in the eastern sector. These results will improve our understanding of hydrology, meteorology, ecology, and paleoclimate reconstructions in the Asian Water Tower region.

Multiobjectivization has emerged as a new promising paradigm to solve single-objective optimization problems (SOPs) in evolutionary computation, where an SOP is transformed into a multiobjective optimization problem (MOP) and solved by an evolutionary algorithm to find the optimal solutions of the original SOP. The transformation of an SOP into an MOP can be done by adding helper-objective(s) into the original objective, decomposing the original objective into multiple subobjectives, or aggregating subobjectives of the original objective into multiple scalar objectives. Multiobjectivization bridges the gap between SOPs and MOPs by transforming an SOP into the counterpart MOP, through which multiobjective optimization methods manage to attain superior solutions of the original SOP. Particularly, using multiobjectivization to solve SOPs can reduce the number of local optima, create new search paths from local optima to global optima, attain more incomparability solutions, and/or improve solution diversity. Since the term ``multiobjectivization'' was coined by Knowles et al. in 2001, this subject has accumulated plenty of works in the last two decades, yet there is a lack of systematic and comprehensive survey of these efforts. This article presents a comprehensive multifacet survey of the state-of-the-art multiobjectivization methods. Particularly, a new taxonomy of the methods is provided in this article and the advantages, limitations, challenges, theoretical analyses, benchmarks, applications, as well as future directions of the multiobjectivization methods are discussed.

A modified in vitro-in vivo correlation (IVIVC) of the oral solid dosage forms has been proposed as a linear correlation between in vitro and in vivo dissolution. Nevertheless, the analysis of in vivo dissolution is limited by the lack of available methods. In this proof-of-concept study, a novel pharmacokinetic (PK) model containing the in vivo dissolution process and its quantification was presented to directly estimate the in vivo dissolution rate constant (kd). The new model was validated with a hypothetical oral solution (kd → +∞). The accuracy of the new method was clarified by comparing with the relatively true value of kd from the literature. Isosorbide mononitrate (ISMN) was used as a model drug to explore the practicability of the novel method. The dissolution capacities of ISMN reference and test tablets were discriminated by an improved in vitro dissolution method. Following the human PK studies, the kd values and corresponding in vivo dissolution profiles of two formulations were obtained using the novel method. Finally, a modified level A IVIVC between in vitro and in vivo dissolution of ISMN tablets was established, which is expected to guide the optimization of the tablet formulation containing ISMN.

Immunoglobulin M (IgM) is the primary antibody in fish, which is transported from epithelial cells into the external secretion system by polymeric immunoglobulin receptor (pIgR). In this study, the full length of IgM and pIgR complementary DNA sequences from leopard coral grouper (Plectropomus leopardus) was characterized, and their expression levels under Vibrio harveyi infection were studied. cDNA sequence analysis showed that the pl-IgM heavy chain cDNA contained an open reading frame (ORF) of 1797 bp encoding a polypeptide of 597 amino acids consisting of a signal peptide, a variable region, and 4 constant regions. pl-pIgR (1041 bp) encodes 346 amino acids with 2 Ig-like domains (ILDs). The expression levels of pl-IgM and pl-pIgR in healthy fish were mainly in the intestine and spleen of fish, which indicates the relationship between the mucosal-associated lymphoid tissue and system lymphoid tissue. Messenger RNA (mRNA) expression profiles of pl-IgM and pl-pIgR were significantly increased in the intestine, head kidney, spleen, and liver after V. harveyi infection. The cDNA sequences of two ILDs were cloned and expressed in Escherichia coli BL21 (DE3). The recombinant pl-pIgR protein had antibacterial function against V. harveyi and Vibrio alginolyticus at 200 ng/μl. Our results indicate that pl-IgM and pl-pIgR are involved in the mucosal-associated immune and systemic immune response in the antibacterial immunity of leopard coral grouper.