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Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose. [ABSTRACT FROM AUTHOR]

Meniscal tears are the most common injury of the knee. Tears of medial meniscus are seen more frequently as compared to lateral meniscus. Most often tears result from sports injuries where there is a twisting motion on the partially flexed, weight-bearing knee. As the majority of our population resides in peripheries where access to arthroscopy and imaging modalities is difficult so we need a clinical test for evaluation of medial meniscal tears. And then this technique can be opted in our practice for early diagnosis of meniscal tears to take proper management for reducing morbidity of these particularpatient, if its diagnostic accuracy comes out to high. Objective: To determine the diagnostic accuracy of McMurray test in diagnosing medial meniscal tears, taking arthroscopy as gold standard. Material and Methods: ThisCross-sectional validation study was carried out in Orthopedic Department of Hospital from September 2020 to August 2021. In this study a total of 149 patients were observed. McMurray test was performed by a single and same consultant and was looked for medial meniscal tear (present/absent) .After this arthroscopy was done in each patient by the consultant orthopedic surgeon who has examined the patient and presence or absence of medial meniscal tear was noted. McMurray test results were compared with arthroscopy result. Results: In this study mean age was 30 years with SD ± 11.35.85% patients were male and 15% patients were female. Diagnostic accuracy of Mcmurray Test findings taking arthroscopy as gold standard was analyzed as the sensitivity was 76.55%, specificity was 75%, Positive predictive value was 99.10%, Negative predictive value was 8.10%. So the overall diagnostic accuracy was 76.51%. Conclusion: This study concludes that the McMurray test had sensitivity 76.55%, specificity 75%, Positive predictive value 99.10%, Negative predictive value 8.10% and the diagnostic accuracy 76.51% in diagnosis of meniscal tear keeping knee arthroscopy as gold standard. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the results of definitive treatment with uniplanar external fixator in open fracture management of tibia in terms of healing. Material and Methods: This case series study was conducted from January 2017 to December 2022 in Akbar Medical Center Dabgari Garden, Peshawar Pakistan. A total number of 97 patients of either gender having age range of 15 to 60 years with open fracture of tibia were included. All patients were admitted horn outpatient department of the center. All the data collected was entered and analyzed with help of SPSS version 23. The results were evaluated using association for the study and application of the methods of Ilizarov (ASAMl) scoring system. Results: There was total 97 patients having age range of44(15-59) with mean age 31.23.(Std Deviation 11.58). Male patients were 74(76.3%) while female were 23(23.7%). Delayed union was noted in 11 (11.3%), External Rotation in 3(3.1%) Healed without complication in 72(74.2%), Infection in 4(4.1%), one pin broken in 4 (4.1%) and Shortening of less than 1.5 cm was noted 3(3.1%) cases. In 4(4.1%) cases debridement was done as secondary procedure, in one case NAfixator was applied 1(1%) while in 7(7.2%) case bone grafting was done as secondary procedure Conclusion: External fixator is used as a definitive treatment method for open fractures of the tibial shaft caused by high energy trauma either in war times or in motor vehicle accidents has good bone and functional results. [ABSTRACT FROM AUTHOR]

Drug solubility plays a significant role in the development of drug formulation. The objectives of this work are to improve the solubility and dissolution rate of vortioxetine (VT) by preparing its inclusion complexes (ICs) with β‐Cyclodextrin (β‐CD) and γ‐Cyclodextrin (γ‐CD). The ICs were prepared in 1:1 M ratio via recrystallization method and characterized by P‐XRD, FT‐IR, 1H NMR, 2D NOESY, and DSC. Further, the crystal structure of VT‐β‐CD was analyzed by SC‐XRD. P‐XRD data obtained for ICs describe the crystalline pattern. The DSC analysis shows change in the thermal behavior of VT, CDs and ICs. FT‐IR analysis shows shifting of frequencies in ICs when compared with the pristine VT drug and CDs. The 2D NOESY in DMSO‐d6 indicates weak interaction between the VT and CD molecules. The crystal structure of VT‐β‐CD consists of one guest VT, one host CD, and nine water molecules in the crystal lattice. The solubility of ICs was significantly improved in distilled water, pH 1.2 acidic, and phosphate buffer pH 6.8 medium, as compared with the solubility of the pristine VT drug. The in vitro dissolution rate of ICs in different dissolution media was investigated, which was higher than that of the commercial product of VT. [ABSTRACT FROM AUTHOR]

Introduction: Subtrochanteric femur fractures have a bimodal age distribution. Younger patients sustain a subtrochanteric fracture as a result of a high-energy injury and typically they have associated traumatic injuries while in older age it is due to low quality of bone. Objective: To determine the functional outcome after proximal femoral nailing for subtrochanteric fracture of femur. Material and Methods: This descriptive case series study was carried out in the Department of Orthopedics Surgery, Medical Teaching Institute, Lady Reading Hospital, Peshawar Pakistan from September 2020 till March 2021 on total of 79 patients to determine the functional outcome after proximal femoral nailing for subtrochanteric femur fractures. Sampling technique was non-probability consecutive sampling. Results: In this study age distribution among 79 patients was analyzed as n= 20-30 years 18(22.8%) 31-40 years 19 (24.1%) 41-50 years 24(30.4%)51-60 years 18(22.8%). Mean age was 47 years with SD±2.87. Gender wise distribution among 79 patients male were 58(73.4%) and female were 21(26.6%). Distribution of duration of disease among 79 patients were analysed as n=1-2 weeks were 58(73.4%) and 3-4 weeks were 21(26.6%). Distribution of BMI classification among 79 patients were analysed as n=Below 18.5 Underweight was 58(73.4%) and 18.5-24.9 Normal weight was 21(26.6%) distribution of functional outcome among 79 patients were analysed as n= Excellent was 30(38.0%) Good was 25(31.6%) Fair was 20(25.3%) and Poor was 4(5.1%). Conclusion: The post-operative clinical and radiological outcome suggests that proximal femoral nail is a exceptional device for treatment of fracture subtrochanteric femur. Although technically demanding, it avoids extensive soft tissue dissection and iatrogenic bony avascularization thus decrease the incidence of fracture non-union and implant failure and at the same time provide much more axial stability due to its intramedullary placement thus it allows the patients to move relatively early following surgery. [ABSTRACT FROM AUTHOR]

With the rapid increase of compute intensive tasks and workload, the need of the hour is to manage the total workload due to resource constraints and increased cost. For complex computations where multiple computer systems are required to execute a single task such as in federated cloudlet environment, load balancing is the main challenge. Load balancing means to divide the total workload between all the member nodes to get the maximum benefits from the federated environment. A cloudlet is a resourceful computer that is coupled to the Internet and is accessible to the mobile devices in the vicinity. Cloudlet Federation is the concept of a cooperative framework to share resources and load balancing among various member cloudlets. Different tasks consume different amount of energy for their execution that results in a large amount of heat dissipation. Due to heat, the performance of the systems is decreased. The more heat, the more performance degradation, so it becomes very vital to keep the energy consumption as minimum as possible. To address this problem, this paper proposes a novel scheduling strategy that will distribute the total load between all the member nodes in a federated cloudlet environment for load balancing. The proposed methodology not only considers the energy level of the system on which the task has to be executed but also considers the energy required by the tasks in queue. The proposed methodology is tested in a Cloudlet Federation environment and the results show an improved load balancing in terms of energy consumption. [ABSTRACT FROM AUTHOR]

The presence of inorganic and organic substances may alter the physicochemical properties of iron (Fe) salt precipitates, thereby stabilizing the antimony (Sb) oxyanions in potable water during the chemical treatment process. Therefore, the present study aimed to examine the surface characteristics, size of Fe flocs and coagulation performance of Sb oxyanions under different aqueous matrices. The results showed that surface properties of Fe flocs significantly varies with pH in both Sb(III, V) suspensions, thereby increasing the mobility of Sb(V) ions in alkaline conditions. The negligible change in surface characteristics of Fe flocs was observed in pure water and Sb(III, V) suspension at pH 7. The key role of Van der Waals forces of attraction as well as hydration force in the aggregation of early formed flocs were found, with greater agglomeration capability at higher more ferric chloride dosage. The higher Sb(V) loading decreased the size of Fe flocs and reversed the surface charge of precipitates, resulting in a significant reduction in Sb(V) removal efficiency. The competitive inhibition effect on Sb(III, V) removal was noticed in the presence of phosphate anions, owing to lowering of ζ-potential values towards more negative trajectory. The presence of hydrophobic organic matter (humic acid) significantly altered the surface characteristics of Fe flocs, thereby affecting the coagulation behavior of Sb in water as compared to the hydrophilic (salicylic acid). Overall, the findings of this research may provide a new insight into the variation in physicochemical characteristics of Fe flocs and Sb removal behavior in the presence of inorganic and organic compounds during the drinking water treatment process. [ABSTRACT FROM AUTHOR]

We show that all of the Schützenberger complexes of an Adian inverse semigroup are finite if the Schützenberger complex of every positive word is finite. This enables us to solve the word problem for certain classes of Adian inverse semigroups (and hence for the corresponding Adian semigroups and Adian groups). [ABSTRACT FROM AUTHOR]

We prove that an inverse semigroup over an Adian presentation is E-unitary. [ABSTRACT FROM AUTHOR]

In this study, we estimated the prevalence of food allergy in the adult allergic patients of Rawalpindi and Islamabad , Pakistan, based on self-report, skin prick test (SPT) and oral food challenge test (OFC). SPT was used for the estimation of sensitization to wheat, egg, milk, beef, chicken, mutton, fish, corn, lentils, rice, soya, peanut and banana. Among 689 patients, 39.19 % showed sensitivity to one or more foods, where, sensitization to wheat (156; 22.6 %) was highest, followed by egg (148; 21.48 %) and milk (138; 20.03 %). Sensitization to various proteins ranged between 15.53-15.97 %, while lentils, corn, rice, soya and peanut sensitization was 15.4, 16, 12.5, 12 and 11.5 % respectively. Only 7.1 % patients were SPT positive for banana allergen. SPT was performed in patients with self-reported food allergy (341/689) and also with no self-reported history of food allergy (348/689). SPT results were positive in 69.8 % of the self-report group, whereas, in the patients with no self-reported food allergy 9.2 % were found sensitized to one or more tested food allergens. 101 patients were recruited for OFC, 61 % of these were confirmed of food allergy. The prevalence of food allergy in the study population was 9 %. Food specific OFC results show that wheat allergy is affecting 1.6 % (95 % CI 0.9-2.84 %) of the total allergy patients, followed by egg allergy 1.31 % (95 % CI 0.70-2.47 %). Furthermore, corn allergy, rice allergy and peanut allergy were 1.02, 0.87 and 0.73 %, respectively. In conclusion, wheat allergy is the most prevalent, followed by egg, chicken, beef and fish allergy, respectively. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to find out functional outcome in patients with distal radius fractures irrespective of radiographic deformities after close reduction and cast splint age. Design: Case series study. Setting: Department of Orthopedics and Spine Surgery, Hayatabad Medical Complex Peshawar. Period: May 2010 to April 2015. Materials and Methods: 28 consecutive patients of either sex with age above 40 years, having distal radius fracture. Functional outcome was assessed with disability of arm, shoulder and hand (DASH) and Patient Rated Wrist/Hand Evolution (PRWHE) questionnaire. Results: Out of 28 patients male were 12(42.9%) and female were 16(57.1%). minimum age was 40 maximum 81 and average was 50. Right side was involved in 17 (60.7%) while left side was involved in 11(39.3%). The DASH Score Record shows that no Disability was seen in 13(46.4%), Minimal Disability in 7(25%), Mild Disability in 5(17.9%), Moderate Disability in 1(3.6%) and Severe Disability in 2(7.1%) patients. While the PRWHE Score Record shows that no Disability was seen in 14(50%), Minimal Disability in 6(21.4%), Mild Disability in 5(17.9%), Moderate Disability in 1(3.6%) and Severe Disability in 2(7.1%) patients. Conclusion: A majority of the distal radius fractures can achieve good results after treatment by closed reduction and cast immobilization, for which conservative treatment should be the first choice. Deformity of the distal radius cannot affect the functional outcome of the wrist and hand. [ABSTRACT FROM AUTHOR]

Abstract: In this work, an experimental investigation into the effects, in terms of energy, of employing a dedicated mechanical subcooling cycle with a residential 1.5ton simple vapor compression refrigeration system is presented. A comparative analysis of the experimental cycle performance is conducted with and without the dedicated subcooler cycle when the room temperature is kept between 18 and 22°C. This is done in order to ascertain the percentage increase in efficiency due to use of a dedicated subcooling loop. R22 is employed as the refrigerant in the main cycle whereas R12 is flowing in the dedicated subcooling cycle. The experimental outcomes indicate that the load carrying capacity of the evaporator increased by approximately 0.5kW when R22 was subcooled, in the main cycle, by 5–8°C. It was also noted that, by using the subcooling, the second-law efficiency of the cycle increased by an average of 21%. Furthermore, the general trend indicated that this percentage increase is inversely proportional to the ambient temperature variation. The experimental work proves that dedicated subcooling can be used for increasing cooling capacity and efficiency. [Copyright &y& Elsevier]

Arsenic (As)-laden wastewater may pose a threat to biodiversity when released into soil and water bodies without treatment. The current study investigated the sorption properties of both As(III, V) oxyanions onto iron hydroxide (FHO) by chemical coagulation. The potential mechanisms were identified using the adsorption models, ζ-potential, X-ray diffraction (XRD) and Fourier Transform Infrared Spectrometry (FT-IR) analysis. The results indicate that the sorption kinetics of pentavalent and trivalent As species closely followed the pseudo-second-order model, and the adsorption rates of both toxicants were remarkably governed by pH as well as the quantity of FHO in suspension. Notably, the FHO formation was directly related to the amount of ferric chloride (FC) coagulant added in the solution. The sorption isotherm results show a better maximum sorption capacity for pentavalent As ions than trivalent species, with the same amount of FHO in the suspensions. The thermodynamic study suggests that the sorption process was spontaneously exothermic with increased randomness. The ζ-potential, FT-IR and XRD analyses confirm that a strong Fe-O bond with As(V) and the closeness of the surface potential of the bonded complex to the point of zero charge (pHzpc) resulted in the higher adsorption affinity of pentavalent As species than trivalent ions in most aquatic conditions. Moreover, the presence of sulfates, phosphates, and humic and salicylic acid significantly affected the As(III, V) sorption performance by altering the surface properties of Fe precipitates. The combined effect of charge neutralization, complexation, oxidation and multilayer chemisorption was identified as a major removal mechanism. These findings may provide some understanding regarding the fate, transport and adsorption properties onto FHO of As oxyanions in a complex water environment. [ABSTRACT FROM AUTHOR]

The widespread usage of nano-copper oxide particles (nano-CuO) in several industrial products and applications raises concerns about their release into water bodies. Thus, their elimination from drinking water is essential to reduce the risk to human health. This work investigated the removal of nano-CuO from pure water and montmorillonite clay (MC) suspensions using poly aluminum ferric chloride (PAFC) as well as cationic polyacrylamide (PAM) by the coagulation-flocculation-sedimentation (C/F/S) process. Moreover, the PAFC and PAFC/PAM flocculation performance for various nano-CuO particles concentrations, dosages, pH, settling times and stirring speeds were also investigated. The findings showed that the removal of nano-CuO and turbidity in MC suspension were higher as compared to pure water. Moreover, the combined effect of PAFC/PAM on the elimination of nano-CuO and turbidity was also substantially better than the individual use of PAFC or PAM. The efficient removal of CuO was observed in the solution containing higher mass concentration in the order (10 mg/L > 2.5 mg/L > 1 mg/L) with an increased coagulant dose. The improved removal performance of nano-CuO was observed in a pH range of 7–11 under various water matrices. The C/F/S conditions of nano-CuO were further optimized by the Box–Behnken statistical experiment design and response surface methodology. The PAFC/PAM dose resulted in the maximum removal of nano-CuO (10 mg/L) in both pure water (>97%) and MC suspension (>99%). The results of particle monitoring and Fourier transform infrared of composite flocs revealed that the main removal mechanism of nano-CuO may be the combined effect of neutralization, complexation as well as adsorption. [ABSTRACT FROM AUTHOR]

The increased utilization of CuO nanoparticles (CuO NPs) in various fields has raised concerns about their discharge into water containing a wide range of organic ligands. Moreover, the adsorption of these ligands can stabilize the CuO NPs in drinking water treatment plants. Thus, their removal from potable water is important to mitigate the risk to humans. The present study explored the efficacy of the coagulation–sedimentation (C/S) process for the removal of tannic acid (TA)-stabilized CuO NPs using polyaluminum ferric chloride (PAFC) as a coagulant. Moreover, the influence of process conditions (stirring speed) and water chemistry (i.e., pH and ionic strength (IS)) were also investigated to determine their impact on removal. The results showed that stirring speed in the reaction phase significantly affected the removal due to increased flocculation compared with stirring speed in the mixing phase. In addition, pH and IS affect the colloidal stability and removal efficiency of CuO NPs. A relatively better removal performance (<99%) of CuO NPs was found at lower coagulant dosage in the pH range 6–8. The addition of organic ligands reversed the surface charge potential and enhanced the colloidal stability of CuO NPs, resulting in the destabilization of TA-CuO NPs, thereby reducing the optimum PAFC dosage for removal. By contrast, the IS above the critical coagulation concentration decreased the removal efficiency due to inhibition of the ionic activity of PAFC hydrolysate in the aqueous environment. Fourier transform infrared findings of TA-CuO NPs composite flocs suggest that the primary removal mechanism might be mediated via the combined effect of neutralization, complexation as well as adsorption. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cancer is multifaceted and influenced by genetic and environmental variables, affecting health, society, and the economy. • Materials science advances, especially metal–organic frameworks (MOFs), have improved cancer detection, diagnosis, and treatment. • MOFs are adaptable carriers for medicinal chemicals and precise cancer cell targeting tools. • MOFs can release medicinal substances reacting to stimuli, enabling externally controlled cancer treatments. • It also addresses intelligent nanobiomaterials' problems and possible uses in cancer treatment delivery systems. Cancer is a complex disease that develops due to complex interactions between hereditary and environmental variables. This devastating disease has far-reaching consequences for human health, communities, and the economy. Therefore, there is a pressing need to improve techniques for detecting, diagnosing, and treating cancer. In recent times, the discipline of materials science has witnessed a significant advancement in metal–organic frameworks, more frequently referred to as MOFs. Metal-organic frameworks (MOFs) have recently garnered considerable attention owing to their immense potential and adaptability in various applications. Notably, they have shown great promise as effective carriers for delivering therapeutic compounds and as precise tools for targeting cancer cells. The intentional manipulation of metal–organic frameworks (MOFs) has endowed them with the distinct ability to selectively release pharmaceutical agents in response to particular stimuli. This attribute has significant potential for the development of externally controlled cancer treatments. This review highlights the current developments in MOF synthesis, highlighting the unique properties that make MOFs ideal for therapeutic applications. We will delve deeply into the benefits of these innovations, focusing on how they can be used in cancer therapy. We will also closely examine their challenges and the potential future applications of intelligent nanobiomaterials in cancer medicine delivery systems. [ABSTRACT FROM AUTHOR]

Metal nanoparticles (NPs) have emerged as crucial components in precision drug delivery, presenting innovative opportunities to significantly enhance therapeutic efficacy and targeting accuracy. This review investigates recent developments in the engineering of metal NPs, emphasizing their distinctive properties and novel applications in drug delivery systems. A comprehensive analysis is performed on gold, silver, iron, and zinc oxide NPs, emphasizing their exceptional physicochemical properties and enhanced drug‐loading capacities. These features collectively enable the development and implementation of targeted and controlled drug delivery systems, indicating a new era of advanced therapeutic approaches. This review article accomplishes this by reflecting on the transformative potential of metal NPs, envisioning heightened efficacy, minimized side effects, and improved patient outcomes within the dynamic landscape of drug delivery platforms. [ABSTRACT FROM AUTHOR]

The quality and level of groundwater tables have rapidly declined because of intensive pumping in Punjab (Pakistan). For sustainable groundwater supplies, there is a need for better management practices. So, the identification of potential groundwater recharge zones is crucial for developing effective management systems. The current research is based on integrating seven contributing factors, including geology, soil map, land cover/land use, lineament density, drainage density, slope, and rainfall to categorize the area into various groundwater recharge potential zones using remote sensing, geographic information system (GIS), and analytical hierarchical process (AHP) for Punjab, Pakistan. The weights (for various thematic layers) and rating values (for sub-classes) in the overlay analysis were assigned for thematic layers and then modified and normalized using the AHP. The result indicates that about 17.88% of the area falls under the category of very high groundwater potential zones (GWPZs). It was found that only 12.27% of the area falls under the category of very low GWPZs. The results showed that spatial technologies like remote sensing and geographic information system (GIS), when combined with AHP technique, provide a robust platform for studying GWPZs. This will help the public and government sectors to understand the potential zone for sustainable groundwater management. [ABSTRACT FROM AUTHOR]

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are highly conserved endogenous single-stranded non-coding RNA molecules that play a crucial role in regulating gene expression to maintain normal physiological functions in fish. Nevertheless, the specific physiological role of miRNAs in lower vertebrates, particularly in comparison to mammals, remains elusive. Additionally, the mechanisms underlying the control of antiviral responses triggered by viral stimulation in fish are still not fully understood. In this study, we investigated the regulatory impact of miR-1388 on the signaling pathway mediated by IFN regulatory factor 3 (IRF3). Our findings revealed that following stimulation with the viral analog poly(I:C), the expression of miR-1388 was significantly upregulated in primary immune tissues and macrophages. Through a dual luciferase reporter assay, we corroborated a direct targeting relationship between miR-1388 and tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Furthermore, our study demonstrated a distinct negative post-transcriptional correlation between miR-1388 and TRAF3. We observed a significant negative post-transcriptional regulatory association between miR-1388 and the levels of antiviral genes following poly(I:C) stimulation. Utilizing reporter plasmids, we elucidated the role of miR-1388 in the antiviral signaling pathway activated by TRAF3. By intervening with siRNA-TRAF3, we validated that miR-1388 regulates the expression of antiviral genes and the production of type I interferons (IFN-Is) through its interaction with TRAF3. Collectively, our experiments highlight the regulatory influence of miR-1388 on the IRF3-mediated signaling pathway by targeting TRAF3 post poly(I:C) stimulation. These findings provide compelling evidence for enhancing our understanding of the mechanisms through which fish miRNAs participate in immune responses. [ABSTRACT FROM AUTHOR]

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response. [ABSTRACT FROM AUTHOR]

This work provides design and characterization of millimeter wave reflectarray antenna based on unit cells as well as periodic reflectarray design at 26 GHz. Diverse unit cell design configurations have been investigated based on simulations and scattering parameter measurements for feasibility of designing an optimum performance 5G reflectarray antenna. It has been demonstrated that the rectangular patch element provided minimum reflection loss of 1.02 dB and maximum bandwidth of 560 MHz. However, the phase error for rectangular patch element was observed to be 80°, which is much higher as compared to 10° and 13° in the case of rectangular ring and circular ring elements respectively. Periodic reflectarray antennas were also designed with main beam focused at 40° in the azimuth plane achieved with tilted array instead of using an offset feed. Radiation pattern measurements were carried out for further characterization where a maximum gain of 26.7 dB was provided by reflectarray designed with circular ring elements with variable radius. On the other hand, rectangular patch element array provided higher 1 dB gain drop bandwidth of 13.6% as compared to circular ring element reflectarray, which demonstrated a bandwidth of 13.1%. However, side lobe levels were observed to be higher at −18.4° for rectangular patch element reflectarray as compared to −19.4° in the case of circular ring elements based reflectarray antenna. [ABSTRACT FROM AUTHOR]

The process of coagulation and precipitation affect the fate and mobility of antimony (Sb) species in drinking water. Moreover, the solubility and physico-chemical properties of the precipitates may be affected by the media chemistry. Accordingly, the present study aimed to investigate the removal of Sb(III, V) species by ferric chloride coagulation under various water chemistry influences with a particular focus on the role of the properties of the precipitates. The results indicated that the amount of Sb(III) removed increased with increasing solution pH, showing the insignificant effects of the hydrodynamic diameter (HDD) and ζ-potential of the precipitates. However, no Sb(V) removal occurred at alkaline pH values, while a highly negative ζ-potential and the complete dissolution of precipitates were observed in the aqueous solution. The solution pH was also useful in determining the dominant coagulation mechanisms, such as co-precipitation and adsorption. The Fe solubility substantially affects the Sb removal at a certain pH range, while the HDD of the precipitates plays an insignificant role in Sb removal. The presence of divalent cations brings the ζ-potential of the precipitates close to point of zero charge (pzc), thus enhancing the Sb(V) removal at alkaline pH conditions. Pronounced adverse effects of humic acid were observed on Sb removal, ζ-potential and HDD of the precipitates. In general, this study may provide critical information to a wide group of researchers dealing with environmental protection from heavy metal pollution. [ABSTRACT FROM AUTHOR]

The co-occurrence of arsenic (As) and organic ligands in water bodies has raised environmental concerns due to their toxicity and adverse effects on human health. The present study aims to elucidate the influences of hydrophobic/hydrophilic organic ligands, such as humic acid (HA) and salicylic acid (SA), on the interactive behavior of As species in water. Moreover, the competitive removal behaviors of As(III, V) species and total organic carbon (TOC) were systematically investigated by coagulation-flocculation-sedimentation (C/F/S) under various aqueous matrices. The results showed the stronger binding affinity of As(V) than As(III) species, with a higher complexation ability of hydrophobic ligands than hydrophilic. The media containing hydrophilic ligands require smaller ferric chloride (FC) doses to achieve the higher As(III, V) removal, while the optimum FC dose required for As(III) removal was found to be higher than that for As(V). Moreover, hydrophobic ligands showed higher TOC removal than hydrophilic ligands. The pronounced adverse effect of a higher concentration of hydrophobic ligands on the removal efficiencies of As(V) and TOC was observed. The adsorption of As(V) on Fe precipitates was better fitted with the Langmuir model but the Freundlich isotherm was more suitable for As(III) in the presence of hydrophilic SA. Moreover, TOC removal was substantially decreased in the As(V) system as compared to the As(III) system due to the dissolution of Fe precipitates at higher As(V) concentrations. The results of FC composite flocs demonstrated that the combined effect of oxidation, charge neutralization and adsorption played an important role in the removal of both toxicants during the C/F/S process. In summary, the findings of the present study provide insights into the fate, mobility and competitive removal behavior of As(III, V) species and organic ligands in the water treatment process. [ABSTRACT FROM AUTHOR]

The increased use of engineered nanoparticles (ENPs), such as copper oxide nanoparticles (CuO NPs), in commercial products and applications raises concern regarding their possible release into freshwater sources. Therefore, their removal from water is important to eliminate adverse environmental and human health effects. In this study, the effects of pH and natural organic matter (NOM), i.e., humic acid (HA) and salicylic acid (SA) on the removal of CuO NPs by coagulation/flocculation/sedimentation (C/F/S) were evaluated. The results indicated that pH significantly affects the coagulation efficiency, where 10–60% CuO NPs removal was achieved under extreme acidic/alkaline conditions. However, at neutral pH, removal of up to 90% was observed with a lower ferric chloride (FC) dosage (0.2 mM). The coagulation efficiency and mechanism were strongly affected by the type of Fe species present in the aqueous phase, which is mainly controlled by pH. Higher concentrations of both HA and SA decrease the CuO NPs agglomeration rate, and thereby improve the colloidal stability due to the NOM molecules adsorbed onto the NPs surface. The presence of hydrophobic HA needs a higher FC dosage of 0.5–0.8 mM than a dosage of hydrophilic SA of 0.25–0.35 mM, to obtain a similar CuO coagulation efficiency. Moreover, higher removals of dissolved organic carbon (DOC) and UV254 were observed more in hydrophobic NOM than in hydrophilic. The results of the Fourier transform infrared (FT-IR) analysis of FC composite flocs confirm that the charge neutralization and enmeshment of coagulant might be a possible removal mechanism. The findings of the current study may provide critical information in the prediction of the fate, mobility, and removal of CuO NPs during C/F/S in water treatment. [ABSTRACT FROM AUTHOR]

The use of zinc oxide nanoparticles (ZnO NPs) and polybrominated diphenyl ethers (PBDPEs) in different products and applications leads to the likelihood of their co-occurrence in the aquatic system, making it important to study the effect of PBDPEs on the fate and transport of ZnO NPs. In this study, we determine the influence of PBDPEs (BDPE-47 and BDPE-209) on the colloidal stability and physicochemical properties of ZnO NPs in different aqueous matrices. The results indicated the shift in ζ potential of ZnO NP from positive to negative in the presence of both PBDPEs in all tested waters; however, the effect on the NPs surface potential was specific to each water considered. The lower concentration of the PBDPEs (e.g., 0.5 mg/L) significantly reduced the ζ potential and hydrodynamic diameter (HDD) of ZnO NP, even in the presence of high content of dissolved organic matter (DOM) in both freshwater and industrial wastewater. Moreover, both BDPE-47 and BDPE-209 impede the agglomeration of ZnO NP in simple and natural media, even in the presence of monovalent and polyvalent cations. However, the effect of BDPE-47 on the ζ potential, HDD, and agglomeration of ZnO NP was more pronounced than that of BDPE-209 in all tested waters. The results of Fourier transform infrared (FT-IR) and X-ray Photon Spectroscopy (XPS) further confirm the adsorption of PBDPEs onto ZnO NP surface via aromatic ether groups and Br elements. The findings of this study will facilitate a better understanding of the interaction behavior between the ZnO NPs and PBDPEs, which can reduce the exposure risk of aquatic organisms to both pollutants. [ABSTRACT FROM AUTHOR]

In most countries, arsenic (As) and antimony (Sb) are regulated pollutants, due to their significant impacts on the environment and human health. Iron-based (Fe) coagulants play a fundamental role in the removal of both elements from aqueous media. This study aims to investigate the competitive removal of As and Sb in relation to Fe solubility. Coagulation experiments were conducted in synthetic water under various pH and contaminant loading, using ferric chloride (FC) as a coagulant. In the single system, the pentavalent species significantly reduced the Fe solubility and thereby enhanced the mobility of As and Sb under these environmental conditions. The coexistence of pentavalent and trivalent species in the binary system considerably decreases the Fe solubility at acidic conditions while enhancing the dissolution under alkaline conditions, thus affecting the overall removal of both species. The presence of four redox species in the quaternary system decreases the Fe solubility remarkably over a wide pH range, with better Sb removal, as compared to As under similar conditions. The adsorption study of the single system showed a decrease in As(V) adsorption capacity at higher concentration, while in the binary system, the Sb(III) showed strong adsorption potential, compared to other species. In the quaternary system, the presence of all four redox species has a synergistic effect on total Sb adsorption, in comparison to the total As. Furthermore, the results of Fourier transform infrared (FT-IR) analysis of FC composite contaminant flocs confirm that the combined effect of charge neutralization and inner sphere complexation might be a possible removal mechanism. These findings may facilitate the fate, transport and comparative removal of redox species in the heterogeneous aquatic environment. [ABSTRACT FROM AUTHOR]

The post-reaction separation in heterogeneous catalysis always remained a point of concern for nanoparticle application in an aqueous medium. This study corroborates the immobilization of TiO2 nanoparticles (NPs) on various solid supports such as activated carbon (AC), zeolite (Z), and ceramics (CCTO) materials. Economically viable and facile impregnation methods were employed to obtain a high mass yield (up to 95%) of immobilized TiO2 NPs. The characterizations of tailored materials were performed by using XRD, BET, UV-Vis DRS, SEM, and pH of the point of zero charges (pHpzc) analyses. The immobilization of TiO2 NPs significantly altered the physicochemical properties and ultimately enhanced the photocatalytic activities under ordinary compact fluorescent light (CFL). To investigate the photocatalytic performance of immobilized materials, model dyes e.g., Methyl Orange (MO) and Methylene Blue (MB) were considered in addition to the heavy metal ions i.e., Cd2+. The immobilization of TiO2 on solid supports revealed better performance for all tshree systems; whereby the AC@TiO2 exhibited higher efficiency as compared to the counterparts i.e., Z@TiO2 and CCTO@TiO2. In binary solutions (MB:Cd2+ and MO:Cd2+), the synergistic effect of the photo-generated positive hole scavenger (MB) and electron trapper (Cd2+) further enhances the removal efficiencies. The regeneration studies showed similar performance as that of the fresh samples, whereby the photocatalytic efficiencies were found to decrease for the consecutive cycles. The immobilization of titania NPs on various solid supports such as activated carbon, zeolite, and ceramics revealed the better photocatalytic performances of the immobilized materials. Moreover, the immobilization affected the bandgap energies for better photocatalytic performances under visible light. [ABSTRACT FROM AUTHOR]

Objectives: To determine the diagnostic accuracy of Ottawa rule in ankle and midfoot fracture keeping x-ray as gold standard. Study Design: Descriptive study. Setting: Department of Orthopedics, Lady Reading Hospital Peshawar. Period: June 2014 to May 2016. Materials and Methods: Through a Cross Sectional Study Design, a total of 175 patients presenting with suspicion of ankle/mid foot fracture were selected in a consecutive manner from the OPD and subjected to detection of fracture through Ottawa Ankle Rule followed by X-ray to confirm the diagnosis of fracture. Results: The mean age group of patients in our study was 36.1+10.4 years. There were 85.7% males and 14.3% were females. The sensitivity analysis shows OAR has a sensitivity of 81.2% and specificity 61.9%., positive predictive value of the OAR is 79.1% and negative predictive value is 65.0% keeping X-ray as a gold standard. Conclusion: The overall sensitivity and specificity of the OAR lies within an acceptable range in our local population however, we still recommend further research work over it before recommendations as a routine screening test for the fracture of ankle or mid foot. [ABSTRACT FROM AUTHOR]

Mycobacterium avium subsp. avium (MAA) is the main tuberculosis pathogen of poultry and wild birds. MAA can also infect mammals such as pigs, cattle, and horses and can pose a threat to people with low immunity. Here, we describe the first identification of MAA strain HJW isolated from a cow in Jilin Province, China. The isolate was completely sequenced and a phylogenetic analysis of its relationship to members of the Mycobacterium avium complex (MAC) was performed. The results revealed that strain HJW was type MAA based on the analysis of insertion sequence amplification and whole genome sequencing. The HJW genome size was 4,961,843 bp with a GC content of 69.28%. The strain was genetically most closely related to the Mycobacterium avium subsp. avium strain DSM 44156. This study suggests that MAA may pose an infection risk to cattle and provides data support for the phylogeny of Mycobacterium avium. [ABSTRACT FROM AUTHOR]

The science of hydrological modeling has continuously evolved under the influence of rapid advancements in software and hardware technologies. Starting from simple rational formulae for estimating peak discharge and developing into sophisticated univariate predictive models, accurate conversion of rainfall into runoff and the assessment of inherent uncertainty has been a prime focus for researchers. Therefore, alternative data-driven methods have gained widespread attention in hydrology. Moreover, scientists often couple conventional machine learning models with data pre-processing techniques, i.e., wavelet transformation (WT), to enhance modelling accuracy. In this context, this research work attempts to explore the latent linkage between rainfall and runoff in Pothohar region of Pakistan by developing a novel linkage of five streamline techniques of machine learning, including single decision tree (SDT), decision tree forest (DTF), tree boost (TB), multilayer perceptron (MLP), and gene expression modeling (GEP), with a more sophisticated variant of WT, i.e., maximal overlap discrete wavelet transformation (MODWT), for boundary correction of the transformed components of timeseries data. This study also implements these machine learning models in a stand-alone mode for a more comprehensive comparative analysis of performances. Furthermore, the study uses a combined-basin approach that divides Pothohar region into two basins to compensate for the complex topographic division of the study area. The results indicate that MODWT-based DTF outperformed other stand-alone and hybrid models in terms of modeling accuracy. In the first scenario, considering the Bunha-Kahan River basin, MODWT-DTF yielded the highest NSE (0.86) and the lowest RMSE (220.45 mm) and R2 (0.92 at lag order 3 (Lo3)) when transformed with daubechies4 (db4) at level three. While in the Soan-Haro River basin, MODWT-DTF produced the highest accuracy modeling at lag order 4 (Lo4) (NSE = 0.88, RMSE = 21.72 m3/s, and R2 = 0.91). The highly accurate performance of 3- and 4-days lagged models reflects the temporal consistency in hydrological response of the study area. The comparison of simple and hybrid model performance indicates up to a 55% increase in modeling accuracy due to data pre-processing with wavelet transformation. [ABSTRACT FROM AUTHOR]

A novel polysaccharide (NCVP-F) from Lactobacillus -fermented Nostoc commune Vauch. was obtained to investigate its underlying mechanism in cadmium-induced kidney injury. Results indicated that in comparison with NCVP, NCVP-F with lower molecular weight of 365.369 kDa, exhibited higher mole percentage of Man and Glc-UA, whereas slightly lower mole percentage of other monosaccharides. NCVP-F is a α-pyran polysaccharide similar to NCVP. Meanwhile, NCVP-F can more effectively alleviate hepatorenal injury (ALT, AST, TG, BUN and SCr) and kidney tissue lesions in Cd-injured mice model by increasing antioxidant enzyme activity (SOD, GSH and GSH-Px), inhibiting cytokines levels (IL-6, IL-1β, TNF-α and IL-18). In addition, NCVP-F effectively inhibited apoptosis proteins (Bax, cytochrome c , a-caspase-9 and a-caspase-3) and enhanced anti-apoptotic protein (Bcl-2) probably via activating PI3K/AKT/mTOR pathway in the Cd-injury kidney. Furthermore, 16S rRNA sequencing results indicated that NCVP-F better enriched Lachnospiraceae , reduced Muribaculaceae , Alloprevotella and Blautia to regulate Cd-induced gut microbiota disorders, which was probably down-regulated 7 pathways including apoptosis and lipopolysaccharide biosynthesis, and up-regulated 63 pathways, such as carbohydrate metabolism and lipid metabolism. This study suggested that applying functional NCVP-F prepared by biotransformation with low molecular weight might be more beneficial. [Display omitted] • A novel polysaccharide (NCVP-F) from Lactobacillus -fermentated N. commune has low M W. • NCVP-F exhibits better effect than NCVP on attenuating Cd-induced kidney injury. • NCVP-F may inhibit apoptosis by PI3K/AKT/mTOR pathway in Cd-injury kidney. • NCVPs enriched different gut microbiota involved in different metabolic pathways. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the factors for preferring the traditional bone setters by people. Study Design: Observational study. Setting: Department of Orthopedics and Spine Surgery Hayatabad Medical Complex Peshawar. Period: October, 2013 to March, 2014. Materials and Methods: Sixty consecutive patients who presented at orthopedics out-patient clinic after attending Traditional Bone Setting Centers were recruited for the study. Information about the patients' bio data, mechanism of injury, who advised them to contact TBS and what are the factors that compelled them to attend TBS were obtained and filled into prepared proforma. The data obtained was recorded and analyzed on SPSS version 17.Results: The mean age was 25.57 years with minimum age 5 years and maximum 65 years. Sixteen patients were females and 44 were male. Two (3.3%) patients first attended Modern orthopedic services (MOS) and 58(96.7%) patients attended TBS.47(78.3%) patients were taken by their own immediate family members to TBS, 20% were referred by friends and 1.7% were self-referral. Thirty seven (61.7%) opted for TBS because of their belief, 11(18.3%) considered this service cheap, 7(11.7%) attended it because it is quick service and 5 (8.3%) reverted to TBS because of attitude of hospital personals. Conclusion: A considerable of people still have great trust on TBS regarding management of musculoskeletal problems. Belief is the most leading cause of consulting traditional bonesetters, other causes include low cast, quick service and attitude of hospital personnel. [ABSTRACT FROM AUTHOR]

Group 1 allergens of Dermatophagoides farinae (Der f 1) and D. pteronyssinus (Der p 1) dominate overall allergic responses in house dust mite allergy patients. The need for accurate identification and characterization of representative variants of group 1 allergens in any given geographic locality has been emphasized for development of appropriate allergen extracts. Regional amino acid sequence polymorphism has been described but the extent of this polymorphism is not well understood. Such data are completely absent for the USA and many other countries. Most previous studies used cDNA libraries generated by reverse transcriptase (RT-PCR) and/or primers amplifying shorter fragments of this gene. Using novel species-specific primers and direct PCR, we document group 1 allergen gene sequence polymorphism in populations of D. farinae and D. pteronyssinus from the USA and Pakistan. We report two novel introns (nt pos 87 and 291) in both species, and the absence of intron 3 in Der p 1. Thirteen silent and one novel non-synonymous mutation (Tryptophan W197 to Arginine R197) were detected in D. farinae. The potential medical significance of the latter mutation is discussed. Two haplotypes of the Der f 1 gene were identified, haplotype 1 (63%) was more frequent than haplotype 2 (18%). Polymorphism in Der f 1 displayed geographical localization, since both haplotypes were present in mite populations from Pakistan whereas haplotype 1 was observed only in the USA. In Der p 1, a silent mutation at nt (aa) position 1011(149) and four non-synonymous mutations at positions 589(50), 935(124), 971(136), 1268(215) were observed. These mutations were reported from many other geographic regions, suggesting that polymorphism in the Der p 1 gene is panmictic. The extent of polymorphism in both genes is substantially lower than that reported previously (0.10–0.16% vs 0.31–0.49%), indicating the need for careful evaluation of potential polymerase errors in studies utilizing RT-PCR. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of a polysaccharide from Rosa rugosa Thunb. on human cervical cancer cells (HCCCs) and the underlying mechanism. Here, a novel Rosa rugosa polysaccharide, named as RRP, was purified from Rosa rugosa petals. RRP consisted of glucose, galacturonic acid, mannose, rhamnose, galactose, arabinose, xylose, and glucuronic acid (molar ratio: 7.78:7.59:4.23:3.22:3.15:1.65:1.00), with Mw of 327.92 kDa. RRP remarkably inhibited cell proliferation, migration, and cell cycle arrest in HeLa and SiHa cells. Furthermore, RRP induced apoptosis by activating the caspase family of proteins and mediating the reactive oxygen species (ROS)-mediated mitochondrial pathway. In addition, RRP was found to dose-dependently induce autophagy, which occurred prior to apoptosis. RRP also primarily induced autophagy-mediated apoptosis in HCCCs via the PI3K/AKT/mTOR pathway. Thus, RRP might serve as a legitimate therapeutic drug candidates against human cervical cancer. • Rosa rugosa polysaccharide (RRP) was purified, which was a kind of pyranose with a molecular weight of 329.72 kDa. • RRP induced mitochondrial apoptosis by activating the caspases family as well as regulated cell cycle in HCCCs. • RRP induced autophagy and promoted the autophagosome accumulation in RRP-induced apoptosis in HCCCs. • RRP induced autophagy-mediated apoptosis in HCCCs via inhibiting the PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC–MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability. [ABSTRACT FROM AUTHOR]

Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level. Herein, we have developed a liposomal carrier co-loaded with SN38 and lovastatin (SL@Lip), which can be accumulated in tumors and efficiently released SN38 and lovastatin, addressing the problem of weak solubility of these two drugs. Importantly, lovastatin can increase DNA damage and enhance the activation of cGAS-STING pathway, coordinating with SN38 chemotherapy and exhibiting the enhanced combinational immunotherapy of PD-1 antibody by remodeling the tumor microenvironment in mouse colorectal cancer of both subcutaneous and orthotopic xenograft models. Overall, this study demonstrates that lovastatin-assisted cGAS-STING stimulation mediated by liposomal delivery system significantly strengthened both chemotherapy and immunotherapy of colorectal cancer, providing a clinically translational strategy for combinational ICB therapy in the "immunologically cold" tumors. • This innovative combination enhances cGAS-STING activation, by lovastatin-mediated impairment of DNA repair. • This approach remodels the tumor microenvironment, strengthening both chemotherapy and immunotherapy. • It offers a clinically translational strategy for tackling 'immun-cold' tumors and advancing ICB therapy. [ABSTRACT FROM AUTHOR]

Given the serious threat of foodborne multidrug-resistant bacteria to animals and humans, finding an effective antibacterial compound has always been an important topic for scientists. Here, from the soil of Changbaishan, we have identified a bacterium that can inhibit the growth of Staphylococcus aureus. Nr genome database analysis and phylogenetic analysis showed that strain CB6 belongs to Bacillus velezensis. We found that the crude extract of strain CB6 has broad-spectrum antibacterial activity against foodborne pathogens. In addition, we showed that the crude extract loses antibacterial activity after treatment with papain. Next, strain CB6 was purified using ammonium sulfate precipitation, a Sephadex G-75 gel filtration column and high-performance liquid chromatography system (HPLC). Liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis indicated that the antibacterial compound was the protein ATP synthase subunit α (ATP-1), with a molecular weight of 55.397 KDa. Moreover, we reported the complete genome sequence of strain CB6, which is composed of a unique circular 3,963,507 bp chromosome with 3749 coding genes and a G + C content of 46.53%. The genome contained 12 gene clusters with antibacterial functions, which constituted over 20.947% of the complete genome. Of note, the amino acid sequence encoding the ATP-1 protein in the strain CB6 genome was identified. In addition to these findings, we speculate that the ATP-1 protein may provide energy for secondary metabolites, which in turn will improve the antibacterial activity of the secondary metabolites. All the above important features make the ATP-1 as a potential candidate for the development of new antibacterial drugs and food preservatives in the future. [ABSTRACT FROM AUTHOR]

Recently, new cationic antibacterial peptide OM19R has been designed with low minimum inhibitory concentration (MIC) values against some gram-negative bacteria, such as Escherichia coli , Salmonella, and Shigella. However, this hybrid peptide, like most antibacterial peptides, has low enzyme stability and short half-life, which, in turn, increases the drug's cost. In this study, an antibacterial peptide (OM19r-8) was obtained containing some D-Arg amino acids. The new preparations were carried out through the replacement of l -Arginine by d -Arginine and the addition of PEG chains. Firstly, eight OM19r series of antibacterial peptides were obtained by designing D-Arg. Then, a polyethylene glycol-modified product mPEG 5 -butyrALD-OM19r-8 (mPEG 5 -OM19r-8) was isolated and purified by reverse-phase high-performance liquid chromatography (RT-HPLC). The enzyme stability test showed that the resistance of antibacterial peptide OM19r-8 to protease degradation increased by 4-32-fold. Moreover, the Time-kill studies showed that the germicidal kinetics curves of mPEG 5 -OM19r-8 and OM19r-8 to Escherichia coli had a similar trend, thus suggesting that PEG modification has an acceptable effect on the activity of the original peptide. Furthermore, the elimination of half-life (28.09 ± 2.81min) of mPEG 5 -OM19r-8, and the area under the drug concentration-time curve (2686.48 ± 651.36min∗ug/ml) was significantly prolonged. The current study demonstrates an example that optimizes the AMP by utilizing L-to-D amino acid replacement and including PEG chains. These results provide useful data for the clinical application of the mPEG 5 -OM19r-8. [ABSTRACT FROM AUTHOR]

This study aimed to fabricate new and effective material for the efficiency of phosphate adsorption. Two types of adsorbent materials, the zirconium hydroxides embedded in pomegranate peel (Zr/Peel) and zirconium-lanthanum hydroxides embedded in pomegranate peel (Zr–La/Peel) were developed. Scanning electronic microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD) were evaluated to give insight into the physicochemical properties of these adsorbents. Zr–La/Peel exceeded the adsorption efficiency of Zr/Peel adsorbents in batch adsorption experiments at the same pH level. The peel as a host can strive to have a strong "shielding effect" to increase the steadiness of the entrenched Zr and La elements. La and Zr are hydroxide metals that emit many hydrogen ions during the hydrolysis reaction, which contribute to protonation and electrostatic attraction. The highest adsorption capacity of La–Zr/Peel for phosphate was calculated to be 40.21 mg/g, and pseudo second-order equation is very well fitted for kinetic adsorption. Phosphate adsorption efficiency was reduced by an increase of pH. With the background of coexisting Cl−, little effect on adsorption efficiency was observed, while adsorption capacities were reduced by almost 20–30% with the coexistence of SO 4 2 − , NO 3 − and humic acid (HA). Image 1 • Designed a new type of biosorbent containing bimetallic hydroxide nanocomposite. • Zr–La/Peel has excellent adsorption capacity under langmuir isotherm model. • Adsorption mechanism, SEM, XRD, and XP Spectroscopy were characterized. • Spent adsorbent material can be desorbed by NaOH treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare effectiveness of hematoma block versus general anesthesia in close reduction of distal radius fractures. Study design: Randomized control tjrial. Place and duration of study: Department of Orthopedic Surgery, Lady Reading Hospital, Peshawar from June 2017 to December 2017. Material and Methods: Patients meeting the inclusion criteria and presenting to Accident and Emergency department were included in the study. Patients were randomly allocated to group-A (hematoma block) and group-B (general anesthesia) by randomization block method. Writt en informed consent was also obtained from all patients. Patient history and radiological assessment was done before anesthesia. Venous catheter was placed for all patients. Vital signs stability was evaluated in terms of pulse rate, respiratory rate, blood pressure, and oxygen saturation. General anesthesia was induced in all patients using propofol 1.5 - 2 mg/kg, and sevoflurane (1% - 1.5%) in-oxygen was applied during general anesthesia. In hematoma block method, 10 mL of lidocaine 1% was injected into the fracture aft er aspiration of fracture hematoma. 10 mL of lidocaine 1% was injected into styloid radius and ulnar side as pinning locations. The maximum dose of 5 mg/kg was used for patients. The area was sterilized using povidone iodine 7.5% before injection. All patients were asked to fast for at least 6 hours. Manipulation through ligmentotaxis was carried out 15 minutes aft er hematoma block and immobilization by cast elbow in ulnar deviation was performed for all patients. For the patients in both groups, acetaminophen-codeine (500 mg/15 mg) tablet was prescribed for the pain aft er procedure, and 30 mg intravenous ketorolac was injected in case of severe pain. Pain intensity in patients was graded and based on visual analogue scale (VAS) in which the score 0 shows no pain and the score 10 indicates the worst imaginable pain. VAS-based pain grades and reduction was assessed aft er 6 hours of surgery. Results: As per effectiveness, in group-A, 34(68%) showed effectives results whereas in group -B, only 14(28%) patients showed effective results. Conclusion: We concluded that hematoma block is more effective than conscious sedation in close reduction of distal radius fracture in term of pain reduction. [ABSTRACT FROM AUTHOR]

The presence of heavy metal (HM) ions, such as lead, cadmium, and chromium in industrial wastewater discharge are major contaminants that pose a risk to human health. These HMs should separate from the wastewater to ensure the reuse of the discharged water in the process and mitigate their environmental impacts. The distinctive mechanical properties of 2D graphene oxide (GO), and the antifouling characteristics of metal oxides (ZnO/NiO) nanoparticles combined to produce composites supporting special features for wastewater treatment. This study employed solution casting and phase inversion methods to synthesize PSF-based GO, ZnO-GO, and ZnO-GO-NiO mixed matrix membranes and the effects of variation in composition on the removal of lead (Pb2+) and cadmium (Cd2+) ion was examined. Several characterization techniques including X-ray diffraction analysis, scanning electron microscopy, energy dispersive X-ray, and Fourier transform infrared spectroscopy were applied to analyze the synthesized NPs and MMMs. The composite membranes were also analyzed in terms of their porosity, permeability, hydrophilicity, surface roughness, zeta potential, thermal stability, mechanical strength, and flux regeneration at various transmembrane pressures (2–3 kgcm−2), and pH value (5.5). The highest adsorption capacities were measured to be 308.16 mg g−1 and 354.80 mg g−1 for Pb (II) and Cd (II), respectively, for membrane (M4_A) having 0.3 wt% of ZnO-GO-NiO nanocomposite, at 200 mg L−1 of feed concentration and 1.60 mL min−1 of permeate flux. The Pb (II) and Cd (II) adsorption breakthrough curves were created, and the results of the experiment were compared with the data of the Thomas model. [Display omitted] • Heavy metal ions in wastewater pose health risks. • Membranes with GO and ZnO–NiO nanocomposite enhance treatment. • Composite membranes analyzed for porosity, permeability, hydrophilicity. • High adsorption capacities of 308.16 mg g−1 for Pb(II), 354.80 mg g−1 for Cd(II) was achieved. [ABSTRACT FROM AUTHOR]

The extraction process of polysaccharides from Flammulina velutipes residue (FVRP) was optimized by the single factor test and response surface methodology with the physical and chemical properties of FVRP determined. The protective effect of FVRP against heavy metals and their mechanism were studied based on Saccharomyces cerevisiae. The results showed that the extraction rate reached 83.7 mg/g with conditions as follows: ultrasonic temperature 75 ℃, extraction time 20 min, material-liquid ratio 1:50 (g/mL), and ultrasonic power 540 W. FVRP with an average molecular weight of 335.3 kDa, containing xylose (17.2 %), galactose (17.0 %), mannose (15.8 %), fucose (9.3 %), arabinose (5.7 %), rhamnose (7.4 %), glucose (8.3 %), galacturonic acid (16.2 %), and glucuronic acid (3.3 %), was obtained under the optimal conditions. FVRP exhibited a strong in vitro antioxidant activity, the scavenging rate on DPPH and ABTS was 55.6 % and 93.9 %, respectively, as FVRP concentration reached 4 mg/mL. Moreover, FVRP significantly rescued the toxicity of heavy metals (cadmium, nickel, and lead) and H 2 O 2 in yeast cells by reducing the overproduction of intracellular reactive oxygen species (ROS). Furthermore, FVRP at the concentration of 0.1 mg/mL still exhibited protective effect in yeast cells against toxicity. Our study built a strong foundation for the reuse and development of FVRP and its protective effect against heavy metal toxicity. [Display omitted] • The extraction process of FVRP was optimized by response surface methodology. • FVRP has in vitro and in vivo anti-toxic effect of heavy metals. • FVRP alleviates heavy metal toxicity by reducing intracellular ROS levels. [ABSTRACT FROM AUTHOR]

Nostoc commune Vauch. polysaccharides (NCVP) was extracted from Nostoc commune Vauch. with strong biological properties. The molecular weight of NCVPs (NCVP, NCVP-S, NCVP-G, and NCVP-I) exhibited a downward trend, and the molar ratio of constituent monosaccharides of NCVPs significantly changed, implying that NCVP could be degraded under in vitro simulated digestion. The antioxidant activities of NCVPs were significantly improved during in vitro digestion. In addition, NCVPs had a prebiotic effect on Lactobacillus strain. During in vitro fermentation, NCVP was degraded and utilized by the gut microbiota, and a variety of short-chain fatty acids (SCFAs) were formed. Functional gene prediction of 16S rDNA sequencing data inferred that NCVP could promote gut metabolism and improve the body's defense mechanism. Overall, these findings emphasized that NCVP is beneficial by maintaining the gut health and can be used as potential prebiotics in the functional foods and medicine industries. [Display omitted] • In vitro digestion of Nostoc commune Vauch. polysaccharides (NCVP) was studied. • Physicochemical properties and biological activity of NCVP significantly changed during gastrointestinal digestion. • NCVP was degraded and utilized by gut microbiota. • The acetic acid, propionic acid and i-butyric acid were on the rise with fermentation time. • NCVP can promote beneficial gut microbiota including Firmicutes and Bacteroidetes. [ABSTRACT FROM AUTHOR]

Ballasted flocculation (BF) is an efficient way to remove the turbidity from surface water. The objective of the present study is to optimize the ballast (magnetite), coagulant (poly aluminum chloride) concentration and pH for efficient turbidity removal from surface water. To do this, the sludge produced from an optimized dose of a BF treatment was utilized for the production of lightweight (LW) aggregates by combining it with hard clay and sewage sludge. The LW aggregates were formed by means of rapid sintering in the temperature range of 1000–1200 °C with an exposure time of 10 min. The physical properties of the LW aggregates, in this case the leaching of heavy metals, the bulk density and the microstructure, were investigated. The results indicated that corresponding ballast and coagulant concentrations of 0.75 g/L and 30 mg/L (poly aluminum chloride (PAC)) resulted in the maximum removal efficiency of ≈95%. Using a mixture of BF sludge (30 wt%), dry sewage sludge (20 wt%), and hard clay (50 wt%), aggregates with a density of around 1.0 g/cm3 could be produced. In addition, it was confirmed that the manufactured aggregate was environmentally stable as the elution of heavy metals was suppressed. [Display omitted] • BF 30 formulation followed the Riley's criteria of LW aggregates manufacturing. • Optimal coagulation conditions were achieved by using PAC and Fe 3 O 4 in BF process. • LW aggregate with BF 30 can be manufactured with a density of less than 1.0g/㎤. • Leaching of heavy metal was suppressed effectively in BF 30 aggregates. [ABSTRACT FROM AUTHOR]