bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of mutations across reverse transcriptase region on HBV replication and progression of liver diseases in Chinese patients
Authors: Lai Xiaoqin , Chen Wenfa , Wu Yuzhu , Gao Yali , Zhang Yalan , Xu Xuwei , Fu Ya , Wang Xinwen , Yang Yanbing , Zhang Yin
Published: June 2022

It was known that mutations in the RT region were mainly related to nucleot(s)ide analogs resistance. Increasing studies indicated that RT mutations were related to advanced liver diseases (ALD) and had effects on HBV replication, but the distribution characteristics of mutations across RT region in the development of liver diseases and the effect of RT mutations on HBV replication were not fully clarified. HBV RT region was direct‐sequenced in 1473 chronic HBV‐infected patients. Mutation frequencies were analyzed to identify the specific mutations differing between groups classified by genotypes, loads of HBV DNA, or progression of liver diseases. In the range of rt145‐rt290, rt145, rt221, rt222, rt267, and rt271 were the genotype‐polymorphic sites, while rt238 was the genotype‐specific sites. Mutations at rt163, rt173, rt180, rt181, rt184, rt191, rt199, and rt214 were more frequent among patients with C‐genotype HBV, while those at rt220, rt225, rt226, rt269, and rt274 were more frequent among patients with B‐genotype HBV. RtM204V/I could reduce the HBV DNA loads while rtQ/L267H/R could increase the HBV DNA loads. RtV214A/E/I (OR 3.94, 95% CI 1.09 to 14.26) was an independent risk factor for advanced liver diseases. In summary, the hotspots of mutations were different between B and C genotypes. Besides the effect on the S region, RT mutations had effects on HBV replication by other unknown ways. RtV214A/E/I was found to be an independent risk factor for ALD, suggesting that mutations at rt214 site could be used as a potential virological marker for the liver disease progression.
Pharmacognostic standardization of Rhododendron afghanicum through scanning electron microscopy and analytical techniques
Authors: Alam Khan , Ahmad Nadeem
Published: June 2022

The aim of this study was to assess and compare the pharmacognostic and microscopic features of the selected parts of Rhododendron afghanicum Aitch. & Hemsl. It is a perennial and shrub. Anatomy of stem and leaves depicted dicot structure. It will provide knowledge about standardization, authentication, and adulteration with its co‐species. The macroscopic examination reveals that fresh leaves are green, pleasant odor with a bitter taste. The leaf is oblong‐elliptic in shape and sub‐acute at apex; rounded at the base with entire margin. Stem is irregular and the outer surface is light brown, rough with fissures and ridges. Microscopic examination indicated the presence of xylem, phloem, peltate trichome, epidermal cells, collenchymas cells, paracytic stomata, and reticulate vessels. Stem microscopy reveals epidermis, hypodermis, cortex, sclerenchymatous sheath, phloem, xylem, and pith. It will be helpful in identification and quality control. Micro‐morphological features were observed through SEM. EDX spectroscopy were carried out and revealed the presence of calcium, silicon, and potassium. Phytochemical analysis revealed the presence of tannins, saponins, phenols, protein, flavonoids, glycosides, and alkaloids. Ethyl acetate for leaf and stem demonstrate the highest extractive values (18% and 13%), respectively. XRD peaks appeared at 30.21, 28.73, 205.73, 200.73, 380.07, 390.24, 490.11, and 450.33ο. This will be helpful to identify the ownership of herbal drugs by the diffraction peaks through crystal structures and atomic spacing. These parameters are crucial for drug identification, standardization, authentication, and drug designing. These studies also provided knowledge regarding therapeutic and nutraceutical importance of this plant.

Research Highlights

The current pharmacognostic studies carried out on Rhododendron afghanicum can serve as a basis for compiling keys for finding the taxonomic identification and authentication of the said species by morphological, anatomical, and physicochemical features.
Input subsidy versus output subsidy for green R&D in a supply chain
Authors: Zhang Yanfang , Tan Qianwen , Ji Yuchang
Published: June 2022

This paper investigates the effects of the government's input subsidy and output subsidy in a green supply chain with a manufacturer and a retailer. We find the input subsidy does not necessarily give rise to a higher R&D input, while the output subsidy does not necessarily lead to a higher output. The comparison is strongly dependent on the externality of the production and consumers' environmental awareness.
Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography
Authors: Crescenzi Rachelle , Donahue Paula M. C. , Garza Maria , Patel Niral J. , Lee Chelsea , Guerreso Kelsey , Hall Greg , Luo Yu , Chen Sheau‐Chiann , Herbst Karen L. , Pridmore Michael , Aday Aaron W. , Beckman Joshua A. , Donahue Manus J.
Published: June 2022

Background

Lipedema exhibits excessive lower‐extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema.

Hypothesis

Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema.

Study Type

Prospective cross‐sectional study.

Subjects

Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment‐related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14).

Field Strength/Sequence

3T MR lymphangiography (nontracer 3D turbo‐spin‐echo).

Assessment

Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features.

Statistical Tests

Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05.

Results

Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11–3.41; diffuse: OR = 0.05, CI = 0.00–1.27), similar in LWL (focal: OR = 1.29, CI = 0.19–8.89; diffuse: OR = 1.05, CI = 0.15–7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30–274.12; diffuse: OR = 5.73, CI = 0.18–186.84).

Data Conclusion

Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema.

Evidence Level

1

Technical Efficacy

Stage 1
Probiotic‐fermented Pueraria lobata (Willd.) Ohwi alleviates alcoholic liver injury by enhancing antioxidant defense and modulating gut microbiota
Authors: Zhao Wenjun , Peng Dong , Li Weijie , Chen Suiying , Liu Bing , Huang Pingxi , Wu Junsong , Du Bing , Li Pan
Published: June 2022

BACKGROUND

Pueraria lobata (Willd.) Ohwi (PL) has been used in China to detoxify alcohol and protect the liver for millennia, though its mechanism of liver protection has not been elucidated. However, fermentation is considered to be one of the effective ways to enhance the efficacy of traditional Chinese medicine. The aim of this study was to investigate the hepatoprotective mechanism of probiotic‐fermented PL (FPL). Sprague Dawley rats were administered with FPL followed by gavage of alcohol for seven consecutive days; following that, liver injury levels were evaluated in rats.

RESULTS

FPL ameliorated lipid accumulation and inflammation levels in rats. Meanwhile, the levels of ethanol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P4502E1 were elevated by FPL treatment. It was observed that the levels of catalase, superoxide dismutase, and glutathione peroxidase were elevated, and the expression of nuclear transcriptional factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase‐1 genes and proteins were increased by FPL treatment, demonstrating that the Nrf2‐mediated signal pathway was activated. Furthermore, FPL restored the composition of the gut microbiota with an increase in the abundances of Firmicutes and Lactobacillus and a decrease in the abundances of Bacteroidota and Akkermansia. Additionally, a strong correlation was found between the gut microbiota and the antioxidant parameters.

CONCLUSION

The results indicate that FPL possesses an excellent protective effect in alcoholic liver injury. Our findings are beneficial to the development of hepatoprotective nutraceuticals for alcoholics. © 2022 Society of Chemical Industry.
Post‐operative Outcomes in Pediatric Patients Following Facial Reconstruction With Fibula Free Flaps
Authors: Slijepcevic Allison A. , Wax Mark K. , Hanasono Matthew , Ducic Yadranko , Petrisor Daniel , Thomas Carissa M. , Shnayder Yelizaveta , Kakarala Kiran , Pipkorn Patrik , Puram Sidharth V. , Rich Jason , Rezaee Rod , Pittman Amy , Troob Scott ,   Head and Neck Reconstruction Group
Published: June 2022

Educational Objective

Assess outcomes of pediatric facial reconstruction with fibula free flaps.

Objectives

Free flap reconstruction of complex maxillofacial defects in pediatric patients is rare. Post‐operative complications, donor site morbidity, impact on craniofacial growth, and oro‐dental rehabilitation are unknown. Our study assesses the outcomes of pediatric maxillofacial reconstruction with composite fibula free flaps.

Study Design

Retrospective chart review.

Methods

Multi‐institutional retrospective chart review from 2000 to 2020 on pediatric patients undergoing maxillomandibular reconstruction with fibula free flaps.

Results

Eighty‐seven patients underwent 89 surgeries; 5 maxillary and 84 mandibular defects. Median age: 12 years. Defects were acquired following resection of sarcoma/carcinoma 44% or benign tumors 50%. 73% of cases had immediate free flap reconstruction. Closing osteotomies were reported in 74%; 1 in 40%, 2 in 27%, and more than 2 in 6.7%. Hardware was used in 98% and removed in 25%. 9.2% demonstrated long‐term hardware exposure, greater than 3 months following reconstruction. Short‐term complications: wound infection 6.7%, flap salvage/failure 2.2%, fistula 1.1%, and compromised craniofacial growth: 23%. Two patients developed trismus. Long‐term fibula donor site complications: hypertrophic scarring: 3.4%, dysesthesia: 1.1%, and long‐term gait abnormality: 1.1%. Dental rehabilitation was performed in 33%. Post‐operative speech outcomes showed 94% with fully intelligible speech.

Conclusion

Pediatric maxillary and mandible defects repaired with fibula free flaps demonstrated complication rates comparable to the adult free flap population. Long‐term follow‐up did not demonstrate adverse outcomes for craniofacial growth. Hardware for flap retention was utilized and remained in place with minimal exposure. Post‐operative gait abnormality is rare.

Level of Evidence

3 Laryngoscope, 133:302–306, 2023
Anxiety, Depression, and Symptom Severity in Patients with Pulsatile and Non‐Pulsatile Tinnitus
Authors: Williams Allison P. , Gourishetti Saikrishna C. , Flaherty Marissa A. , Eisenman David J.
Published: June 2022

Objective(s)

To compare the rates of anxiety and depression between patients with pulsatile (PT) and non‐pulsatile tinnitus (NPT), and their correlation with tinnitus severity.

Methods

A prospective cross‐sectional study of consecutive patients presenting either to the otolaryngology clinic for pulsatile (PT) and NPT or to a tertiary care tinnitus habituation program (THP) were administered the tinnitus handicap inventory (THI), 7‐item general anxiety disorder scale (GAD‐7), and 9‐item patient health questionnaire (PHQ‐9). Median scores between groups and correlation of scores within groups were calculated and compared.

Results

Median THI scores were significantly higher for THP and PT patients as compared with unselected NPT patients (58 and 44 vs. 20, p ≤ 0.001). Median GAD‐7 (10 vs. 2.5 and 2, p ≤ 0.001) and PHQ‐9 (7 vs. 4 and 4, p = 0.04) scores were highest in THP patients compared with PT and NPT. The strongest correlation between tinnitus handicap and psychiatric measures was seen in THP patients.

Conclusion

THP patients report higher levels of anxiety and depression compared with PT and other NPT patients. Tinnitus severity correlates more strongly with GAD‐7 and PHQ‐9 scores in THP patients compared with other patient groups. PT patients have a greater self‐perceived tinnitus handicap than the general cohort of NPT patients, statistically comparable to THP patients. Despite this, anxiety and depression are not more severe in patients with PT as they are in THP patients.

Level of Evidence

2B Laryngoscope, 133:683–688, 2023
Plantation type and afforestation age disclose variable influences on soil microbial compositions in man‐made forests in the Xiong'an New Area, China
Authors: Wang Min , Masoudi Abolfazl , Wang Can , Yang Jia , Zhai Yuepeng , Wu Changhao , Yu Zhijun , Liu Jingze
Published: June 2022

While afforestation helps mitigate climate concerns, the impact of plantation type and afforestation age on soil microbial compositions in afforested areas remains unclear. The current study utilized high‐throughput deep sequencing to investigate the effect of afforestation ages (3 months, 1 year and 6 months, and 15 years) and two different tree species (Pinus tabulaeformis Carr. and Sophora japonica L.) on soil microbiomes and edaphic conditions in afforested plots in the Xiong'an New Area, where soil experienced considerable disturbance by human activities during land preparation. Partial least squares path modelling showed that the afforestation age negatively influenced edaphic conditions. The results of fungal and bacterial biomass showed that bacterial lineages were replaced by fungal lineages as the afforestation age increased. Values of different soil particle sizes were impacted by increased stand ages. PERMANOVA results indicated that the plantation type could significantly explain 35.91% (p = 0.0065) and 23.84% (p = 0.009) of the bacterial and fungal β‐diversity variations, respectively. In contrast, the afforestation age could explain 35.46% (p = 0.017) of the fungal β‐diversity variation significantly. Additionally, our data showed that the co‐occurrence network for P. tabulaeformis plots was more complex than that for S. japonica plots, and network complexity increased with the afforestation age. The above results indicated that plantation type and afforestation age disclose variable influence on soil microbial compositions in man‐made forests in the Xiong'an New Area, China, which provide a basis for subsequent broader framework afforestation programs.
Rheological and tribological evaluation of friction modifiers for wheel‐rail applications
Authors: Leiva‐Mateus Jairo Eduardo , Santa‐Marín Juan Felipe , Buitrago‐Sierra Robison , Mesa Grajales Dairo Hernán , Geffroy E.
Published: June 2022

Friction modifiers (FM's) are substances deliberately applied to the top‐of‐the‐rail in the field in order to control the traction coefficient. In this work, two FM's, a commercial (FM1) and a custom‐made (FM2), and a gauge lubricant (CGL) were evaluated in the laboratory using rheological and tribological tests. Two rheological tests were done: oscillatory (frequency and strain sweeps) and flow tests (viscosity vs. shear rate). Tribological tests were done in a twin disk machine to obtain the traction coefficient under different slip values. Retentivity tests were also done in the same machine. Several physical–chemical tests were also done to characterise the products. The results of rheological tests showed that there are notable differences that can influence the performance of FMs. From the studied materials, the FM2 product tends to be more viscous even for high‐shear rates. The tribological tests showed that the traction coefficient is different for all the studied materials and changes from 0.15 to 0.45 depending on the creepage. The retentivity of FM2 is 1.9 times higher than FM1. The results show a good correlation between the rheological behaviour and the coefficient of traction and retentivity.
In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death
Authors: Mohkam Kayvan , Nasralla David , Mergental Hynek , Muller Xavier , Butler Andrew , Jassem Wayel , Imber Charles , Monbaliu Diethard , Perera M. Thamara P. R. , Laing Richard W. , García‐Valdecasas Juan Carlos , Paul Andreas , Dondero Federica , Cauchy François , Savier Eric , Scatton Olivier , Robin Fabien , Sulpice Laurent , Bucur Petru , Salamé Ephrem , Pittau Gabriella , Allard Marc‐Antoine , Pradat Pierre , Rossignol Guillaume , Mabrut Jean‐Yves , Ploeg Rutger J. , Friend Peter J. , Mirza Darius F. , Lesurtel Mickaël ,   Consortium for Organ Preservation in Europe (COPE)
Published: June 2022

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK–Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End‐Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30‐day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC‐censored 2‐year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.
Getting the Terms Right: Green, Sustainable, or Circular Chemistry?
Authors: Mutlu Hatice , Barner Leonie
Published: June 2022

Green chemistry, sustainable chemistry, and circular chemistry are important concepts for the modern lifestyle, current research directions, and worldwide industries. These three concepts are closely related and interconnected but cannot be used synonymously. In addition, they are addressing two different economic models, i.e., linear economy and circular economy. The current contribution focuses on the importance of these decisive chemistries for the development of a sustainable future and their role in the realm of circular economy and the planetary boundaries framework—especially for the planetary boundary of “novel entities.” Researchers active in the field of polymer chemistry play an important role as plastic pollution and resource in addition to environmental depletion, caused by the still increasing production of polymers and plastics, become more and more pronounced. It is also reported that multi‐ and interdisciplinary approaches are needed to develop solutions for a sustainable future.
Trends in environmental monitoring of high explosives present in soil/sediment/groundwater using LC‐MS/MS
Authors: Mary Celin Senthil , Sharma Bhumika , Bhanot Pallvi , Kalsi Anchita , Sahai Sandeep , Tanwar Rajesh Kumar
Published: June 2022

Environmental contamination by explosives occurs due to improper handling and disposal procedures. Explosives and their transformation products pose threat to human health and the ecosystem. Trace level detection of explosives present in different environmental matrices is a challenge, due to the interference caused by matrix components and the presence of cocontaminants. Liquid chromatography combined with tandem mass spectrometry (LC‐MS/MS) is an advanced analytical tool, which is ideal for quantitative and qualitative detection of explosives and its metabolites at trace levels. This review aims to showcase the current trends in the application of LC‐MS/MS for detecting explosives present in soil, sediment, and groundwater with detection limits ranging from nano to femtogram levels. Specificity and advantages of using LC‐MS/MS over conventional analytical methods and various processing methods and techniques used for sample preparation are discussed in this article. Important application aspects of LC‐MS/MS on environmental monitoring include site characterization and degradation evaluation. Studies on qualitative and quantitative LC‐MS/MS analysis in determining the efficiency of treatment processes and contamination mapping, optimized conditions of LC and MS/MS adopted, role of different ionization techniques and mass analyzers in detection of explosives and its metabolites, relative abundance of various product ions formed on dissociation and the levels of detection achieved are reviewed. Ionization suppression, matrix effect, additive selection are some of the major factors which influence MS/MS detection. A summary of challenges and future research insights for effective utilization of this technique in the environmental monitoring of explosives are presented.
Generalized and optimal sequence of weights on a progressive‐iterative approximation method with memory for least square fitting
Authors: Channark Saknarin , Kumam Poom , Martinez‐Moreno Juan , Chaipunya Parin , Jirakitpuwapat Wachirapong
Published: June 2022

The generalized and optimal sequence of weights on a progressive‐iterative approximation method with memory for least square fitting (GOLSPIA) improves the MLSPIA method by extends to the multidimensional data fitting. In addition, weights of the moving average are varied between iterations, using the three optimal sequences of weights derived from the singular values of the collocation matrix. It is proved that a series of data fitting with an appropriate alternative of weights converge to the solution of least square fitting. Moreover, the convergence rate of the new method is faster than that of the MLSPIA method. Some examples and applications in this paper show the efficiency and effectiveness of the GOLSPIA method.
Approximate controllability of the semilinear population dynamics system with diffusion
Authors: Singh Ajeet , Shukla Anurag
Published: June 2022

This paper aims to study the approximate controllability of semilinear population dynamics system with diffusion using semigroup theory. The semilinear population dynamical model with the nonlocal birth process is transformed into a standard abstract semilinear control system by identifying the state, control, and the corresponding function spaces. The state and control spaces are assumed to be Hilbert spaces. The semigroup theory is developed from the properties of the population operators and Laplacian operators. Then the approximate controllability results of the system are obtained using
‐semigroup approach and some other simple conditions on the nonlinear term and operators involved in the model.
Evaluation of properties and performance of poly(ether sulfone ketone) membranes in proton exchange membrane fuel cells
Authors: Oroujzadeh Maryam , Mehdipour‐Ataei Shahram
Published: June 2022

Two series of sulfonated poly(ether sulfone ketone)s have been synthesized. The effect of different ratios of sulfone: ketone functional groups on the properties and performance of membranes is studied. The density, ion‐exchange capacity, water absorption, swelling ratio, proton conductivity, thermal and oxidative stability of membranes are determined. The results showed that membranes with higher contents of sulfone functional groups show lower density and consequently higher water absorption and swelling ratio values. A precise evaluation of the effect of different sulfone: ketone functional group ratios on the analytical acid concentration and the effective proton mobility and their relationship with water absorption have been performed. The proton conductivity values are between 71–78 mS.cm−1 at 30°C and 117–208 mS.cm−1 at 80°C. The effective proton mobilities at 80°C are in the range of 10.27 × 10 −4 to 16.68 × 10 −4 cm2.V−1.s−1. The highest current density for prepared membranes in H2/O2 single cell at 100% relative humidity and 80°C is 1900 mA.cm−2.
Role effect on beauty premium: Female as proposer may gain more fairness
Authors: Ma Qingguo , Cheng Lu , Qiu Wenwei , Pei Guanxiong
Published: June 2022

Beauty premium permeates every aspect of life. However, whether females' roles, as proposers or as recipients/responders, have an influence on the marginal effect of beauty remains unclear and was explored in the current study. Dictator game and ultimate game were employed to investigate the effect of females' roles on beauty premium from males. Participants played against female recipients and proposers in Study 1. Linear regression models of social preferences with respect to female attractiveness showed a strongly positive marginal effect of beauty, and the effect was significantly higher when participants played against female recipients than female proposers. Study 2 with ultimate games only was conducted for further testing the effect of strategic behavior on beauty premium. A probabilistic method was established to handle issues on comparison between participants' behaviors as proposers and as recipients/responders. The results of these studies suggest that there are significant money forgone differences between females as proposers and as recipients/responders financially regardless of the strategy‐or‐not decision difference. All the findings indicate that the beauty premium varies with female roles.
PTEN‐PI3K pathway alterations in advanced prostate cancer and clinical implications
Authors: Choudhury Atish D.
Published: June 2022

Background

Despite significant advances in molecular characterization and therapeutic targeting of advanced prostate cancer, it remains the second most common cause of cancer death in men in the United States. The PI3K (Phosphatidylinositol 3‐kinase)/AKT (AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin) signaling pathway is commonly altered in prostate cancer, most frequently through loss of the PTEN (Phosphatase and Tensin Homolog) tumor suppressor, and is critical for cancer cell proliferation, migration, and survival.

Methods

This study summarizes signaling through the PTEN/PI3K pathway, alterations in pathway components commonly seen in advanced prostate cancer, and results of clinical trials of pathway inhibitors reported to date with a focus on more recently reported studies. It also reviews rationale for combination approaches currently under study, including with taxanes, immune checkpoint inhibitors and poly (ADP‐ribose) polymerase inhibitors, and discusses future directions in biomarker testing and therapeutic targeting of this pathway.

Results

Clinical trials studying pharmacologic inhibitors of PI3K, AKT or mTOR kinases have demonstrated modest activity of specific agents, with several trials of pathway inhibitors currently in progress. A key challenge is the importance of PI3K/AKT/mTOR signaling in noncancerous tissues, leading to predictable but often severe toxicities at therapeutic doses.

Results

Further advances in selective pharmacologic inhibition of the PI3K/AKT/mTOR pathway in tumors, development of rational combinations, and appropriate biomarker selection to identify the appropriate tumor‐ and patient‐specific vulnerabilities will be required to optimize clinical benefit from therapeutic targeting of this pathway.
Lethal and sublethal effects of chlorantraniliprole on the migratory moths Agrotis ipsilon and A. segetum: New perspectives for pest management strategies
Authors: Zhang Da‐Wei , Dai Chang‐Chun , Ali Abid , Liu Yong‐Qiang , Pan Ye , Desneux Nicolas , Lu Yan‐Hui
Published: June 2022

BACKGROUND

Agrotis ipsilon and A. segetum are major migratory pests of many crops in China, and frequent regional outbreaks cause severe yield losses. Use of food attractants is one of the most promising control methods against adult lepidoptera, notably through the attract‐and‐kill strategy. Chlorantraniliprole's acute toxicity and sublethal effects on both moths were evaluated.

RESULTS

Chlorantraniliprole showed high activity against both adults of both species, with LC20 and LC50 values of 0.08 and 0.21 mg L−1 (A. ipsilon), and 0.14 and 0.51 mg L−1 (A. segetum). The fecundity, effective oviposition rate, and egg hatching rate of both species in dual‐sex exposure treatments were all significantly reduced compared with the control, and the population growth coefficients in the LC50♀ × LC50♂ treatments were only 0.32% (A. ipsilon) and 3.35% (A. segetum) that of the control. Furthermore, the flight distance was significantly suppressed from 6.67 km (control) to 0.01 km (LC50) for A. ipsilon, and from 7.39 km (control) to 0.78 km (LC50) for A. segetum. The proportions of robust‐ and medium‐flight individuals of A. ipsilon and A. segetum in exposure treatments were greatly reduced.

CONCLUSIONS

Low lethal concentration exposures to chlorantraniliprole can drastically reduce the reproduction and flight performance of A. ipsilon and A. segetum, while inhibiting the production of offspring, suggesting chlorantraniliprole would be an excellent compound for use in combination with food attractants. Chlorantraniliprole has good potential for management of the two long‐range migratory pests tested using an attract‐and‐kill strategy. © 2022 Society of Chemical Industry.
Predicting the habitat suitability of the invasive white mango scale,Aulacaspis tubercularis; Newstead, 1906 (Hemiptera: Diaspididae) using bioclimatic variables
Authors: Azrag Abdelmutalab GA , Mohamed Samira A , Ndlela Shepard , Ekesi Sunday
Published: June 2022

BACKGROUND

The white mango scale,Aulacaspis tubercularis(Hemiptera: Diaspididae), is an invasive pest that threatens the production of several crops of commercial value including mango. Though it is an important pest, little is known about its biology and ecology. Specifically, information on habitat suitability ofA. tubercularisoccurrence and potential distribution under climate change is largely unknown. In this study, we used four ecological niche models, namely maximum entropy, random forest, generalized additive models, and classification and regression trees to predict the habitat suitability ofA. tubercularisunder current and future [representative concentration pathways (RCPs): RCP4.5 and RCP8.5 of the year 2070] climatic scenarios, using bioclimatic variables. Models' performance was evaluated using the true skill statistic (TSS), the area under the curve (AUC), correlation (COR), and the deviance.

RESULTS

All models sufficiently predicted the occurrence ofA. tuberculariswith high accuracy (AUC ≥ 0.93, TSS ≥ 0.81 and COR ≥ 0.77). The random forest algorithm had the highest accuracy among the four models (AUC = 0.99, TSS = 0.93, COR = 0.90, deviance = 0.26). Temperature seasonality (Bio4), mean temperature of the driest quarter (Bio9), and precipitation seasonality (Bio15) were the most important variables influencingA. tubercularisoccurrence. Models' predictions showed that countries in east, south, and west Africa are highly suitable forA. tubercularisestablishment under current conditions. Similarly, Mexico, Brazil, India, Myanmar, Bangladesh, Thailand, Laos, Vietnam, and Cambodia are also highly suitable for the pest to thrive. Under future conditions, the suitable areas might slightly decrease in many countries of sub‐Saharan Africa under both RCPs. However, the range of expansion ofA. tubercularisis projected to be higher in Australia, Brazil, Spain, Italy, and Portugal under the future climatic scenarios.

CONCLUSION

The results reported here will be useful for guiding decision‐making, developing an effective management strategy, and serving as an early warning tool to prevent further spread toward new areas. © 2022 Society of Chemical Industry.
To leave or stay? Out‐migration of skilled migrants in Beijing, China
Authors: Hu Lei , Liu Yishuang , Sun Maohua , Lu Qiuhong
Published: June 2022

The out‐migration decision of skilled migrants in first‐tier cities is receiving growing attention from researchers and policymakers in recent years. We conducted a survey on skilled people in Beijing who did not have a household registration (hukou). We employed a Probit model with selection to determine the individual socioeconomic characteristics compelling skilled migrants to remigrate from first‐tier cities to other regions. The analysis results show that the status of housing property ownership and accessibility to children's education are two key factors affecting out‐migration decisions. Accessibility to children's education is primarily limited by the institutional arrangements on hukou, and its pushing effect is marginally greater than that of the status of housing property ownership for out‐migrants leaving Beijing. Our results also indicate that skilled migrants with postgraduate degrees, higher occupation levels and/or better personal and family economic conditions are more likely to remain in Beijing, whereas the relationship between age and probability of out‐migration is inversely U‐shaped. In addition, people living together with family members are more likely to remain in Beijing.
Design of a new adaptive EWMA control chart
Authors: Sarwar Muhammad Atif , Noor‐ul‐Amin Muhammad
Published: June 2022

The memory‐based control charts (CCs) such as exponentially weighted moving average (EWMA) and Cumulative sum (CUSUM) are good for quick detection of small or moderate shifts in the process mean. This study proposes a memory‐based CC to monitor the mean of a normally distributed process. The idea is to estimate the mean shift using an estimator based on an EWMA statistic and after that determine the smoothing constant of plotting EWMA statistics through the proposed continuous function. The performance of the proposed adaptive EWMA (AEWMA) chart is focused on utilizing extensive Monte Carlo simulations method with various shifts in the process mean. Taking into account the run‐length (RL) profiles, as an evaluation tool, the proposed chart is efficient as compared to the competitor charts. The demonstration of the proposed chart is presented by using a real dataset from the manufacturing process of substrates where the quality characteristic is the resistance of flow width.
Differential expression of single‐cell RNA‐seq data using Tweedie models
Authors: Mallick Himel , Chatterjee Suvo , Chowdhury Shrabanti , Chatterjee Saptarshi , Rahnavard Ali , Hicks Stephanie C.
Published: June 2022

The performance of computational methods and software to identify differentially expressed features in single‐cell RNA‐sequencing (scRNA‐seq) has been shown to be influenced by several factors, including the choice of the normalization method used and the choice of the experimental platform (or library preparation protocol) to profile gene expression in individual cells. Currently, it is up to the practitioner to choose the most appropriate differential expression (DE) method out of over 100 DE tools available to date, each relying on their own assumptions to model scRNA‐seq expression features. To model the technological variability in cross‐platform scRNA‐seq data, here we propose to use Tweedie generalized linear models that can flexibly capture a large dynamic range of observed scRNA‐seq expression profiles across experimental platforms induced by platform‐ and gene‐specific statistical properties such as heavy tails, sparsity, and gene expression distributions. We also propose a zero‐inflated Tweedie model that allows zero probability mass to exceed a traditional Tweedie distribution to model zero‐inflated scRNA‐seq data with excessive zero counts. Using both synthetic and published plate‐ and droplet‐based scRNA‐seq datasets, we perform a systematic benchmark evaluation of more than 10 representative DE methods and demonstrate that our method (Tweedieverse) outperforms the state‐of‐the‐art DE approaches across experimental platforms in terms of statistical power and false discovery rate control. Our open‐source software (R/Bioconductor package) is available athttps://github.com/himelmallick/Tweedieverse.
Red‐Light‐Responsive Metallopolymer Nanocarriers with Conjugated and Encapsulated Drugs for Phototherapy Against Multidrug‐Resistant Tumors
Authors: Chen Mingjia , Gong Ningqiang , Sun Wen , Han Jianxiong , Liu Yuanli , Zhang Shouwen , Zheng Aiping , Butt Hans‐Jürgen , Liang Xing‐Jie , Wu Si
Published: June 2022

It is challenging to treat multidrug‐resistant tumors because such tumors are resistant to a broad spectrum of structurally and functionally unrelated drugs. Herein, treatment of multidrug‐resistant tumors using red‐light‐responsive metallopolymer nanocarriers that are conjugated with the anticancer drug chlorambucil (CHL) and encapsulated with the anticancer drug doxorubicin (DOX) is reported. An amphiphilic metallopolymer PolyRuCHL that contains a poly(ethylene glycol) (PEG) block and a red‐light‐responsive ruthenium (Ru)‐containing block is synthesized. Chlorambucil is covalently conjugated to the Ru moieties of PolyRuCHL. Encapsulation of DOX into PolyRuCHL in an aqueous solution results in DOX@PolyRuCHL micelles. The DOX@PolyRuCHL micelles are efficiently taken up by the multidrug‐resistant breast cancer cell line MCF‐7R and which carries DOX into the cells. Free DOX, without the nanocarriers, is not taken up by MCF‐7R or pumped out of MCF‐7R via P‐glycoproteins. Red light irradiation of DOX@PolyRuCHL micelles triggers the release of chlorambucil‐conjugated Ru moieties and DOX. Both act synergistically to inhibit the growth of multidrug‐resistant cancer cells. Furthermore, the inhibition of the growth of multidrug‐resistant tumors in a mouse model using DOX@PolyRuCHL micelles is demonstrated. The design of red‐light‐responsive metallopolymer nanocarriers with both conjugated and encapsulated drugs opens up an avenue for photoactivated chemotherapy against multidrug‐resistant tumors.
Dual‐Atom Nickel Moieties of Ni(II)2N4(µ2‐N)2 Anchored on Alfalfa‐Derived Developed Porous N‐Doped Carbon for High‐Performance Li–S Battery
Authors: Zhang Tengfei , Xiao Hong , Liang Xiao , Zhang Fanchao , Zhuang Huifeng , Gao Qiuming , Zheng Lirong
Published: June 2022

A universal strategy is established for preparing the carbonaceous matrix‐based atomically distributed metal catalysts M‐BPC (M=Ni, Co, Fe, Cu, and Mn, and biomass‐derived porous carbon (BPC)) by one‐step pyrolysis of mixed metal salts and biomass alfalfa. The optimized Ni‐BPC has dual‐atom Ni(II)2N4(µ2‐N)2 moieties, which are chemically anchored on the alfalfa‐derived developed porous N‐doped carbon BPC matrix. An ultrahigh specific surface area of 3133 m2 g−1 with huge total pore volume of 3.02 cm3 g−1 is obtained for Ni‐BPC. The Ni‐BPC could greatly promote the redox kinetics and effectively prevent the shuttle effect of lithium polysulfides in a Li–S battery. The Li–S battery assembled with the Ni‐BPC modified separator exhibits prominent rate performance with the reversible specific capacities of 1279, 1119, 1037, 948 and 787 mAh g−1 at the current densities of 0.1, 0.2, 0.5, 1 and 2 C, respectively. The battery presents an ultra‐long life with low capacity decay of 0.028% per cycle up to 2100 cycles at 1 C. Even under high areal S loadings of 3.9 mg cm−2, the high discharge capacity of 976.6 mAh g−1 is obtained at 0.2 C and excellent cycling stability with 61.1% capacity retention is achieved after 490 cycles.
Magnetically Driven Hierarchical Alignment in Biomimetic Fibrous Hydrogels
Authors: Chen Wen , Zhang Zhaobao , Kouwer Paul H. J.
Published: June 2022

In vivo, natural biomaterials are frequently anisotropic, exhibiting directional microstructures and mechanical properties. It remains challenging to develop such anisotropy in synthetic materials. Here, a facile one‐step approach for in situ fabrication of hydrogels with hierarchically anisotropic architectures and direction‐dependent mechanical properties is proposed. The anisotropic hydrogels, composed of a fibrous gel network (0.1 wt%), cross‐linked with magnetic nanoparticles (spheres, rods, and wires, <0.1 wt%) are readily formed in the presence of very low magnetic fields (<20 mT). The anisotropy of the nanoparticles is transduced to the polymer network, leading to macroscopic anisotropy, for instance, in mechanical properties. Electrostatic repulsion by the negatively charged nanoparticles induces an additional layer of order in the material, perpendicular to the magnetic field direction. The straightforward fabrication strategy allows for stepwise deposition of layers with different degrees or directions of anisotropy, which enables the formation of complex structures that are able to mimic some of the complex hierarchical architectures found in biology. It is anticipated that this approach of hydrogel alignment may serve as a guide for designing advanced biomaterials in tissue engineering.
Novel Strategy for Optimized Nanocatalytic Tumor Therapy: From an Updated View
Authors: Li Zhen-Li , Wu Han , Zhu Jia-Qi , Sun Li-Yang , Tong Xiang-Min , Huang Dong-Sheng , Yang Tian
Published: June 2022

Nanozyme has been experiencing rapid development in biomedical applications involving biosensors, immunoassays, and antitumor agents in recent years due to its tunable catalytic performance and desirable biocompatibility. Since the first exploration of nanozyme‐based Fenton reaction for nanocatalytic therapy (NCT) against tumor, a variety of Fenton (and Fenton‐like) nanozymes, such as Fe3O4, transition metal ions (Co2+, Cu2+, and Mn2+), and metal–organic frameworks (MOFs), have been proved as desirable candidates for tumor therapy, and the modulation of the tumor microenvironment (TME) is determined to be a feasible approach to improve the catalytic efficiency for in situ tumor suppression. At present, increasing studies have focused on improving the therapeutic efficiency of NCT by formulating multifunctional nanozyme‐based systems to satisfy the demand for versatile and optimized applications. Herein, updated insights into the novel strategies of 1) achieving highly effective nanocatalytic reactions, including the modification of nanocatalysts and TME‐modulating approaches, are provided and 2) the design and formulation of multifunctional nanozyme‐based systems which achieve targeted, synergistic therapy, and theranostic applications are analyzed and concluded. Concise and concentrated comments and outlooks are illuminated at the end to outline the perspectives and the remaining challenges for the next‐step explorations on further biomedical translation of NCT.
Encoding Manipulation of DNA‐Nanoparticle Assembled Nanorobot Using Independently Charged Array Nanopores
Authors: Si Wei , Zhu Zhendong , Wu Gensheng , Zhang Yin , Chen Yunfei , Sha Jingjie
Published: June 2022

During the past decades, scientists have developed different kinds of nanorobots based on various driving principles to realize controlled manipulation of them for potential applications like medical diagnosis and directed cargo delivery. In order to design a nanorobot with advantages of simple operation and precise control that can enrich the family of intelligent nanorobots, an encoding manipulation method is proposed to control the movement of a DNA‐nanoparticle assembled nanorobot by combing electrophoresis and electroosmosis effect in independently charged array nanopores. The nanorobot is composed of one nanoparticle and one or two ssDNAs. ssDNAs act as the legs of the nanorobot. The selective ion transport through charged nanopores can induce cooperation and competition between the electroosmosis and electrophoresis, which is the main power to activate the nanorobot. Thus by simply switching the applied electric field and surface charge density of each nanopore which is defined as the encoded nanopore according to a predetermined strategy, the well‐controlled encoding manipulation including capturing, releasing, jumping, and crawling of the nanorobot is realized in this work. The study is expected to realize its value in many interesting applications like drug delivery, nanosurgery, and so on in the near future.
Matrix‐induced sugaring‐out liquid‐liquid microextraction coupled with high‐performance liquid chromatography for the determination of organophosphorus pesticides in fruit jams
Authors: Alkan Cansu , Çabuk Hasan
Published: June 2022

A rapid and easy analytical method for the determination of organophosphorus pesticides (fenitrothion, phosalone, profenofos, and chlorpyrifos) in fruit jams was developed using sugaring‐out liquid‐liquid microextraction followed by high‐performance liquid chromatography with ultraviolet detection. Acetonitrile was the only chemical used in the sample pretreatment step. The high sugar content of the sample matrix highly accelerated the extraction process as it simply triggered phase separation. The optimized sample treatment involved mixing 600 μl of ACN/water mixture (50/50%, v/v) with 1 g of jam sample, shaking for 0.5 min at 2500 rpm, and then centrifuging the sample for 5 min at 2500 × g. Under the optimal conditions, the extraction recoveries in the range of 81%–89% were achieved for the analytes. Good linearity in a range of 50–5000 μg/kg (r2 ≥ 0.9992) and limits of detection less than 25 μg/kg were obtained. Recovery assays for spiked commercial jams made from cherry, strawberry, blackberry, apricot, and blueberry provided recoveries from 89% to 107%.
Ginsenoside Rg1 suppresses paraquat‐induced epithelial cell senescence by enhancing autophagy in an ATG12‐dependent manner
Authors: Huang Changbao , Xue Xiang , Gong Nengkai , Jiang Jinghan
Published: June 2022

Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ‐induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ‐poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ‐induced pulmonary fibrosis and the underlying mechanism. In vivo, the treatment of Rg1 can attenuate PQ‐induced pulmonary fibrosis and decrease senescence and senescence associated secretory phenotype (SASP) expression. In vitro, Rg1 can effectively eliminate senescent cells via apoptosis, but not normal cells. In addition, we demonstrate that Rg1 can enhance autophagy activity via inducing the expression of ATG12. Inhibition of autophagy via 3‐MA or transfection of the siRNA targeting ATG12 can impair the antiaging effect of Rg1. Taken together, our data implicates that Rg1 can protect pulmonary epithelial cells from PQ‐induced cellular senescence in an ATG12 dependent manner, which may provide a preventive and therapeutic strategy for PQ poisoning‐induced pulmonary fibrosis.