The inevitable impacts of climate change have reverberated across ecosystems and caused substantial global biodiversity loss. Climate-induced habitat loss has contributed to range shifts at both species and community levels. Given the importance of identifying suitable habitats for at-risk species, it is imperative to assess potential current and future distributions, and to understand influential environmental factors. Like many species, the Demoiselle crane is not immune to climatic pressures. Khyber Pakhtunkhwa and Balochistan provinces in Pakistan are known wintering grounds for this species. Given that Pakistan is among the top five countries facing devastating effects of climate change, this study sought to conduct species distribution modeling under climate change using data collected during 4 years of field surveys. We developed a Maximum Entropy distribution model to predict the current and projected future distribution of the species across the study area. Future habitat projections for 2050 and 2070 were carried out using two representative concentration pathways (RCP 4.5 and RCP 8.5) under three global circulation models, including HADGEM2-AO, BCC-CSM1-1, and CCSM4. The most influential factors shaping Demoiselle Crane habitat suitability included the temperature seasonality, annual mean temperature, terrain ruggedness index, and human population density, all of which contributed significantly to the suitability (81.3%). The model identified 35% of the study area as moderately suitable (134,068 km2) and highly suitable (27,911 km2) habitat for the species under current climatic conditions. Under changing climate scenarios, our model predicted a major loss of the species\' current suitable habitat, with shrinkage and shift towards western-central areas along the Pakistan-Afghanistan boarder. The RCP 8.5, which is the extreme climate change scenario, portrays particularly severe consequences, with habitat losses reaching 65% in 2050 and 85% in 2070. This comprehensive study provides useful insights into the Demoiselle Crane habitat\'s current and future dynamics in Pakistan.

BACKGROUND: Malaria remains a formidable worldwide health challenge, with approximately half of the global population at high risk of catching the infection. This research study aimed to address the pressing public health issue of malaria\'s escalating prevalence in Khyber Pakhtunkhwa (KP) province, Pakistan, and endeavors to estimate the trend for the future growth of the infection.
METHODS: The data were collected from the IDSRS of KP, covering a period of 5 years from 2018 to 2022. We proposed a hybrid model that integrated Prophet and TBATS methods, allowing us to efficiently capture the complications of the malaria data and improve forecasting accuracy. To ensure an inclusive assessment, we compared the prediction performance of the proposed hybrid model with other widely used time series models, such as ARIMA, ETS, and ANN. The models were developed through R-statistical software (version 4.2.2).
RESULTS: For the prediction of malaria incidence, the suggested hybrid model (Prophet and TBATS) surpassed commonly used time series approaches (ARIMA, ETS, and ANN). Hybrid model assessment metrics portrayed higher accuracy and reliability with lower MAE (8913.9), RMSE (3850.2), and MAPE (0.301) values. According to our forecasts, malaria infections were predicted to spread around 99,301 by December 2023.
CONCLUSIONS: We found the hybrid model (Prophet and TBATS) outperformed common time series approaches for forecasting malaria. By December 2023, KP\'s malaria incidence is expected to be around 99,301, making future incidence forecasts important. Policymakers will be able to use these findings to curb disease and implement efficient policies for malaria control.

The tumor microenvironment (TME) is pivotal in cancer progression and the response to immunotherapy. A \"hot\" tumor typically contains immune cells that promote anti-tumor immunity, predicting positive prognosis. \"Cold\" tumors lack immune cells, suggesting a poor outlook across various cancers. Recent research has focused on converting \"cold\" tumors into \"hot\" tumors to enhance the success of immunotherapy. A prerequisite for the studies of the TME is an accurate knowledge of the cell populations of the TME. This study aimed to describe the immune TME of lung and colorectal cancer and melanoma, focusing on lymphoid and myeloid cell populations. We induced heterotopic immunocompetent tumors in C57BL/6 mice, using KP and LLC (Lewis lung carcinoma) cells for lung cancer, MC38 cells for colorectal cancer, and B16-F10 cells for melanoma. Immune cell infiltration was analyzed using multicolor flow cytometry in single-cell suspensions after tumor excision. KP cell tumors showed an abundance of neutrophils and eosinophils; however, they contained much less adaptive immune cells, while LLC cell tumors predominated in monocytes, neutrophils, and monocyte-derived dendritic cells. Monocytes and neutrophils, along with a significant T cell infiltration, were prevalent in MC38 tumors. Lastly, B16-F10 tumors were enriched in macrophages, while showing only moderate T cell presence. In conclusion, our data provide a detailed overview of the immune TME of various heterotopic tumors, highlighting the variabilities in the immune cell profiles of different tumor entities. Our data may be a helpful basis when investigating new immunotherapies, and thus, this report serves as a helpful tool for preclinical immunotherapy research design.

Keratosis pilaris atrophicans faciei (KPAF) is a rare, hereditary, follicular disorder categorized in the atrophicans subtypes of keratosis pilaris (KP). Nowadays it can be treated with light and laser devices. Lasers with wavelengths <600 nm, especially pulsed dye laser (PDL), are effective for treatments of KPAF. Here, we present a case with KPAF treated with 585 nm diode laser, a kind of laser system functioning with differential wavelength modified optically pumped semiconductor (D-WMOPS) technology. Our case is the first patient reported to have been treated with this laser technology in the literature.

The propagation step is one of the key reactions in radical polymerization and knowledge about its kinetics is often vital for understanding and designing polymerization processes leading to new materials or optimizing technical processes. Arrhenius expressions for the propagation step in free-radical polymerization of diethyl itaconate (DEI) as well as di-n-propyl itaconate (DnPI) in bulk, for which propagation kinetics was yet unexplored, were thus determined via pulsed-laser polymerization in conjunction with size-exclusion chromatography (PLP-SEC) experiments in the temperature range of 20 to 70 °C. For DEI, the experimental data was complemented by quantum chemical calculation. The obtained Arrhenius parameters are A = 1.1 L·mol-1·s-1 and Ea = 17.5 kJ·mol-1 for DEI and A = 1.0 L·mol-1·s-1 and Ea = 17.5 kJ·mol-1 for DnPI.

UNASSIGNED: To elucidate the cellular mechanisms of polyherbal formulation [Kolin PlusTM (KP)], genomics was performed to delineate the genes and pathways associated with lipid regulation through transcriptional profiling of the liver in commercial broilers raised on diets deficient in choline chloride (CCL).
UNASSIGNED: The gene expression patterns were studied for four groups [normal diet: normal, choline chloride deficient (CCD), KP (400 gm/ton), and CCL (400 gm/ton)] using Agilent microarray on day 42. The hierarchical cluster analysis was carried out on 12,614 differentially expressed genes (DEGs) with a similar expression.
UNASSIGNED: Out of 12,614 significant DEGs, 1,926, 448, and 1,330 genes were expressed at higher rates, and 413, 482, and 1,364 were expressed at lower rates than CCD (CCD vs. normal), CCL (CCL vs. CCD), and KP (KP vs. CCD), respectively. GO enrichment analysis of DEG further revealed the significant association of biological process items with the lipid, sterol, and lipoprotein metabolic processes. In particular, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, carnitine palmitoyl transferase I, hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta, and patatin-like phospholipase domain containing 2 genes involved in fatty acid oxidation and lipase C, ABCG5, ABCG8, acetyl-CoA carboxylase, ATP citrate lyase enzyme, and peroxisome proliferator-activated receptor gamma genes involved in lipogenesis were altered by KP intervention for lipid metabolism.
UNASSIGNED: These findings reveal that the supplementation of KP prevents fatty liver-associated problems in broiler chickens by modulating the expression of the above-mentioned genes that are responsible for the oxidation of fatty acids and lipogenesis in the liver.

The aim of this study was to develop physiologically based pharmacokinetic (PBPK) models capable of simulating cefadroxil concentrations in plasma and tissues in mouse, rat, and human. PBPK models in this study consisted of 14 tissues and 2 blood compartments. They were established using measured tissue to plasma partition coefficient (K p) in mouse and rat, absolute expression levels of hPEPT1 along the entire length of the human intestine, and the transporter kinetic parameters. The PBPK models also assumed that all the tissues were well-stirred compartments with perfusion rate limitations, and the ratio of the concentration in tissue to the unbound concentration in plasma is identical across species. These PBPK models were validated strictly by a series of observed plasma concentration-time profile data. The average fold error (AFE) and absolute average fold error (AAFE) values were all less than 2. The models\' rationality and accuracy were further demonstrated by the almost consistent V ss calculated by the PBPK model and noncompartmental method, as well as the good allometric scaling relationship of V ss and CL. The model suggests that hPEPT1 is the major transporter responsible for the oral absorption of cefadroxil in human, and the plasma concentration-time profiles of cefadroxil were not sensitive to dissolution rate faster than T85% = 2 h. The cefadroxil PBPK model in human is reliable and can be used to predict concentration-time profile at infected tissue. It may be useful for dose selection and informative decision-making during clinical trials and dosage form design of cefadroxil and provide a reference for the PBPK model establishment of hPEPT1 substrate.

The present study aims to examine the role of kisspeptin (KP), FSH, and its receptor (FSHR), and their interrelationships in the control of basic human ovarian granulosa cells functions. We investigated: (1) the ability of granulosa cells to produce KP and FSHR, (2) the role of KP in the control of ovarian functions, and (3) the ability of KP to affect FSHR and to modify the FSH action on ovarian functions. The effects of KP alone (0, 10 and 100 ng/mL); or of KP (10 and 100 ng/mL) in combination with FSH (10 ng/mL) on cultured human granulosa cells were assessed. Viability, markers of proliferation (PCNA and cyclin B1) and apoptosis (bax and caspase 3), as well as accumulation of KP, FSHR, and steroid hormones, IGF-I, oxytocin (OT), and prostaglandin E2 (PGE2) release were analyzed by the Trypan blue exclusion test, quantitative immunocytochemistry, and ELISA. KP given at a low dose (10 ng/mL) stimulated viability, proliferation, inhibited apoptosis, promoted the release of progesterone (P4), estradiol (E2), IGF-I, OT, and PGE2, the accumulation of FSHR, but not testosterone (T) release. KP given at a high dose (100 ng/mL) had the opposite, inhibitory effect. FSH stimulated cell viability, proliferation and inhibited apoptosis, promoted P4, T, E2, IGF-I, and OT, but not PGE2 release. Furthermore, KP at a low dose promoted the stimulatory effect of FSH on viability, proliferation, P4, E2, and OT release, promoted its inhibitory action on apoptosis, but did not modify its action on T, IGF-I, and PGE2 output. KP at a high dose prevented and inverted FSH action. These results suggest an intra-ovarian production and a functional interrelationship between KP and FSH/FSHR in direct regulation of basic ovarian cell functions (viability, proliferation, apoptosis, and hormones release). The capability of KP to stimulate FSHR, the ability of FSH to promote ovarian functions, as well as the similarity of KP (10 ng/mL) and FSH action on granulosa cells\' viability, proliferation, apoptosis, steroid hormones, IGF-I, OT, and PGE2 release, suggest that FSH influence these cells could be mediated by KP. Moreover, the capability of KP (100 ng/mL) to decrease FSHR accumulation, basal and FSH-induced ovarian parameters, suggest that KP can suppress some ovarian granulosa cell functions via down-regulation of FSHR. These observations propose the existence of the FSH-KP axis up-regulating human ovarian cell functions.

Transporters can play a key role in the absorption, distribution, metabolism, and excretion of drugs. Understanding these contributions early in drug discovery allows for more accurate projection of the clinical pharmacokinetics. One method to assess the impact of transporters in vivo involves co-dosing specific inhibitors. The objective of the present study was to optimize the dose and route of administration of a P-glycoprotein (P-gp) inhibitor, valspodar (PSC833), and a dual P-gp/breast cancer resistance protein (BCRP) inhibitor, elacridar (GF120918), by assessing the transporters\' impact on brain penetration and absorption. A dual-infusion strategy was implemented to allow for flexibility with dose formulation. The chemical inhibitor was dosed intravenously via the femoral artery, and a cassette of known substrates was infused via the jugular vein. Valspodar or elacridar was administered as 4.5-hour constant infusions over a range of doses. To assess the degree of inhibition, the resulting ratios of brain and plasma concentrations, Kp\'s, of the known substrates were compared to the vehicle control. These data demonstrated that doses greater than 0.9 mg/hr/kg valspodar and 8.9 mg/hr/kg elacridar were sufficient to inhibit P-gp- and BCRP-mediated efflux at the blood-brain barrier in rats without any tolerability issues. Confirmation of BBB restriction by efflux transporters in preclinical species allows for subsequent prediction in humans based upon the proteomic expression at rodent and human BBB. Overall, the approach can also be applied to inhibition of efflux at other tissues (gut absorption, liver clearance) or can be extended to other transporters of interest using alternate inhibitors.

Based on the direct linearization framework of the discrete Kadomtsev-Petviashvili-type equations presented in the work of Fu & Nijhoff (Fu W, Nijhoff FW. 2017 Direct linearizing transform for three-dimensional discrete integrable systems: the lattice AKP, BKP and CKP equations. Proc. R. Soc. A 473, 20160915 (doi:10.1098/rspa.2016.0915)), six novel non-autonomous differential-difference equations are established, including three in the AKP class, two in the BKP class and one in the CKP class. In particular, one in the BKP class and the one in the CKP class are both in (2 + 2)-dimensional form. All the six models are integrable in the sense of having the same linear integral equation representations as those of their associated discrete Kadomtsev-Petviashvili-type equations, which guarantees the existence of soliton-type solutions and the multi-dimensional consistency of these new equations from the viewpoint of the direct linearization.