bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the pathogenicity of BRCA1/2 variants of unknown significance: Relevance and challenges for breast cancer precision medicine
Authors: De Paolis Elisa , Paris Ida , Tilocca Bruno , Roncada Paola , Foca Laura , Tiberi Giordana , D’Angelo Tatiana , Pavese Francesco , Muratore Margherita , Carbognin Luisa , Garganese Giorgia , Masetti Riccardo , Di Leone Alba , Fabi Alessandra , Scambia Giovanni , Urbani Andrea , Generali Daniele , Minucci Angelo , Santonocito Concetta
Published: January 2023

Introduction

Breast cancer (BC) is the leading cause of cancer-related death in women worldwide. Pathogenic variants in BRCA1 and BRCA2 genes account for approximately 50% of all hereditary BC, with 60-80% of patients characterized by Triple Negative Breast Cancer (TNBC) at an early stage phenotype. The identification of a pathogenic BRCA1/2 variant has important and expanding roles in risk-reducing surgeries, treatment planning, and familial surveillance. Otherwise, finding unclassified Variants of Unknown Significance (VUS) limits the clinical utility of the molecular test, leading to an “imprecise medicine”.

Methods

We reported the explanatory example of the BRCA1 c.5057A>C, p.(His1686Pro) VUS identified in a patient with TNBC. We integrated data from family history and clinic-pathological evaluations, genetic analyses, and bioinformatics in silico investigations to evaluate the VUS classification.

Results

Our evaluation posed evidences for the pathogenicity significance of the investigated VUS: 1) association of the BRCA1 variant to cancer-affected members of the family; 2) absence of another high-risk mutation; 3) multiple indirect evidences derived from gene and protein structural analysis.

Discussion

In line with the ongoing efforts to uncertain variants classification, we speculated about the relevance of an in-depth assessment of pathogenicity of BRCA1/2 VUS for a personalized management of patients with BC. We underlined that the efficient integration of clinical data with the widest number of supporting molecular evidences should be adopted for the proper management of patients, with the final aim of effectively guide the best prognostic and therapeutic paths.
Case report: Successful management of a refractory double-expressor diffuse large B-cell lymphoma patient under the guidance of in vitro high-throughput drug sensitivity test
Authors: Xing Lijie , Wang Hui , Liu Dan , He Qiang , Li Zengjun
Published: January 2023

Introduction

Double-expressor diffuse large B-cell lymphoma (DEL), harboring double expression of MYC and BCL2, has an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). We initiated a clinical trial to treat newly diagnosed DEL with R-CHOP plus Bruton’s tyrosine kinase (BTK) inhibitor (BTKi) zanubrutinib (ZR-CHOP) and achieved a high complete response (CR) rate while four patients progressed during therapy, one of them carrying ATM and CD58 mutations. We applied an in vitro high-throughput drug sensitivity test for the prediction of clinical responses to different drugs in this patient.

Case presentation

We report a 30-year-old female patient diagnosed with stage III (DEL), with ATM and CD58 mutations. The patient achieved partial response (PR) after two cycles of ZR-CHOP and remained PR after four cycles of ZR-CHOP, while the disease progressed after six cycles of ZR-CHOP. High-throughput drug screening using a panel of 117 compounds identified a range of therapies with efficacy for this patient. The primary tumor cells showed moderate sensitivity to bortezomib, thalidomide, and gemcitabine as a single agent and bortezomib, thalidomide, and dexamethasone (VTD) as a combined regimen. The patient was treated with two cycles of VTD regimen (bortezomib 1.3 mg/m2, d1, 4, 8, 11; thalidomide 100 mg, d1-21; dexamethasone 20 mg, d1, 2, 4, 5, 8, 9) and achieved PR with only a small lesion left. Another two cycles of VTD plus gemcitabine were then administered, and the patient achieved CR. Stem cells were mobilized, and autologous hematopoietic stem cell transplantation was carried out afterward. The patient remained CR for more than 3 months after transplantation.

Conclusion

In this article, we present a first-line chemoresistant DEL patient with ATM and CD58 mutations who was treated successfully with VTD plus gemcitabine under the guidance of in vitro high-throughput drug sensitivity test.
Analysis of histology-agnostic targets among soft tissue and bone sarcomas in the AACR GENIE database
Authors: Pestana Roberto Carmagnani , Serrano César
Published: January 2023

Background

The development of novel therapies for patients with sarcoma is challenging due to the rarity and diversity of these mesenchymal neoplasms. Hence, histology-agnostic approvals can be of particular interest for the treatment of patients with soft tissue and bone sarcoma.

Methods

We queried the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database Cohort v12.0-Public to investigate the prevalence of currently Food and Drug Administration (FDA)-approved and other potentially actionable histology-agnostic alterations in patients with soft tissue and bone sarcoma. Targets were identified by a literature review by the authors. Results are presented for each cohort identified in the GENIE database, namely: (1) soft tissue sarcoma (STS), (2) gastrointestinal stromal tumor (GIST), (3) bone sarcoma, (4) uterine sarcoma, and (5) breast sarcoma.

Results

We identified 7,512 samples of 6,955 patients with sarcoma in the AAACR GENIE database v12.0-Public. Molecular alterations that could lead to the clinical use of a currently approved histology-agnostic therapy were identified in 2.1% of sarcomas (2.6% STS, 1.3% GIST, 1.4% bone, 2.7% uterine, and 0% breast). In addition, 2.9% of patients could be eligible for future histology-agnostic approvals. These specific mutations, fusions, and amplifications occurred in multiple histotypes in all cohorts.

Discussion

Exploring a public large-scale genomic database, we identified that 5% of patients with sarcoma could be eligible for current histology-agnostic FDA-approved drugs or future potential histology-agnostic indications. These actionable alterations were present in a wide variety of histologies in soft tissue and bone sarcomas, highlighting that next-generation sequencing can be considered for patients with advanced sarcoma to guide treatment strategies.
Whole-lesion histogram analysis of multiple diffusion metrics for differentiating lung cancer from inflammatory lesions
Authors: Li Jiaxin , Wu Baolin , Huang Zhun , Zhao Yixiang , Zhao Sen , Guo Shuaikang , Xu Shufei , Wang Xiaolei , Tian Tiantian , Wang Zhixue , Zhou Jun
Published: January 2023

Background

Whole-lesion histogram analysis can provide comprehensive assessment of tissues by calculating additional quantitative metrics such as skewness and kurtosis; however, few studies have evaluated its value in the differential diagnosis of lung lesions.

Purpose

To compare the diagnostic performance of conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) in differentiating lung cancer from focal inflammatory lesions, based on whole-lesion volume histogram analysis.

Methods

Fifty-nine patients with solitary pulmonary lesions underwent multiple b-values DWIs, which were then postprocessed using mono-exponential, bi-exponential and DKI models. Histogram parameters of the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f), apparent diffusional kurtosis (Kapp) and kurtosis-corrected diffusion coefficient (Dapp) were calculated and compared between the lung cancer and inflammatory lesion groups. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance.

Results

The ADCmean, ADCmedian, Dmean and Dmedian values of lung cancer were significantly lower than those of inflammatory lesions, while the ADCskewness, Kappmean, Kappmedian, KappSD, Kappkurtosis and Dappskewness values of lung cancer were significantly higher than those of inflammatory lesions (all p < 0.05). ADCskewness (p = 0.019) and Dmedian (p = 0.031) were identified as independent predictors of lung cancer. Dmedian showed the best performance for differentiating lung cancer from inflammatory lesions, with an area under the ROC curve of 0.777. Using a Dmedian of 1.091 × 10-3 mm2/s as the optimal cut-off value, the sensitivity, specificity, positive predictive value and negative predictive value were 69.23%, 85.00%, 90.00% and 58.62%, respectively.

Conclusions

Whole-lesion histogram analysis of DWI, IVIM and DKI parameters is a promising approach for differentiating lung cancer from inflammatory lesions, and Dmedian shows the best performance in the differential diagnosis of solitary pulmonary lesions.
Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients
Authors: Jia Bin , Xia Peiyi , Dong Junqiang , Feng Wenhao , Wang Wenjia , Liu Enjie , Jiang Guozhong , Qin Yanru
Published: January 2023

Background

Sarcomatoid hepatocellular carcinoma (SHC) is a rare epithelial malignancy with high invasiveness and poor prognosis. However, the molecular characteristics and main driver genes for SHC have not been determined. The aim of this study is to explore the potentially actionable mutations of driver genes, which may provide more therapeutic options for SHC.

Methods

In this study, DNA extraction and library preparation were performed using tumor tissues from 28 SHC patients. Then we used Miseq platform (Illumina) to sequence the target-enriched library, and we aligned and processed the sequencing data. The gene groups were tested for SNVs/Indels/CNVs. Tumor mutation burden (TMB) was assessed by the 425-cancer-relevant gene panel. Multivariate analysis of COX’s model was used for survival analysis (OS) of patients’ clinical characteristics.

Result

The median overall survival (OS) of the patients was only 4.4 months. TP53, TERT, and KRAS were the top three frequently mutated genes, with frequencies of 89.3%, 64.3%, and 21.4%, respectively. A considerable number of patients carried mutations in genes involved in the TP53 pathway (96%) and DNA Damage Repair (DDR) pathway (21%). Multiple potentially actionable mutations, such as NTRK1 fusions and BRCA1/2 mutations, were identified in SHCs.

Conclusions

This study shows a landscape of gene mutations in SHC. SHC has high mutation rates in TP53 pathway and DDR pathway. The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC.
Prognostic risk analysis related to radioresistance genes in colorectal cancer
Authors: Qin Haoren , Zhang Heng , Li Haipeng , Xu Qiong , Sun Wanjun , Zhang Shiwu , Zhang Xipeng , Zhu Siwei , Wang Hui
Published: January 2023

Background

Radiotherapy (RT) is one of the most important treatments for patients with colorectal cancer (CRC). Radioresistance is the crucial cause of poor therapeutic outcomes in colorectal cancer. However, the underlying mechanism of radioresistance in colorectal cancer is still poorly defined. Herein we established a radioresistant colorectal cancer cell line and performed transcriptomics analyses to search for the underlying genes that contribute to radioresistance and investigate its association with the prognosis of CRC patients.

Methods

The radioresistant cell line was developed from the parental HCT116 cell by a stepwise increased dose of irradiation. Differential gene analysis was performed using cellular transcriptome data to identify genes associated with radioresistance, from which extracellular matrix (ECM) and cell adhesion-related genes were screened. Survival data from a CRC cohort in the TCGA database were used for further model gene screening and validation. The correlation between the risk score model and tumor microenvironment, clinical phenotype, drug treatment sensitivity, and tumor mutation status were also investigated.

Results

A total of 493 different expression genes were identified from the radioresistant and wild-type cell line, of which 94 genes were associated with ECM and cell adhesion-related genes. The five model genes TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1 were identified for CRC radioresistance via screening using the best model. A ROC curve indicated that the AUC of the resulting prognostic model (based on the 5-gene risk score and other clinical parameters, including age, sex, and tumor stages) was 0.79, 0.77, and 0.78 at 1, 2, and 3 years, respectively. The calibration curve showed high agreement between the risk score prediction and actual survival probability. The immune microenvironment, drug treatment sensitivity, and tumor mutation status significantly differed between the high- and low-risk groups.

Conclusions

The risk score model built with five radioresistance genes in this study, including TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1, showed favorable performance in prognosis prediction after radiotherapy for CRC.
Modelling metastatic colonization of cholangiocarcinoma organoids in decellularized lung and lymph nodes
Authors: van Tienderen Gilles S. , van Beek Marije E. A. , Schurink Ivo J. , Rosmark Oskar , Roest Henk P. , Tieleman Jantine , Demmers Jeroen , Muntz Iain , Conboy James , Westergren-Thorsson Gunilla , Koenderink Gijsje , van der Laan Luc JW , Verstegen Monique M. A.
Published: January 2023

Cholangiocarcinoma (CCA) is a type of liver cancer with an aggressive phenotype and dismal outcome in patients. The metastasis of CCA cancer cells to distant organs, commonly lung and lymph nodes, drastically reduces overall survival. However, mechanistic insight how CCA invades these metastatic sites is still lacking. This is partly because currently available models fail to mimic the complexity of tissue-specific environments for metastatic CCA. To create an in vitro model in which interactions between epithelial tumor cells and their surrounding extracellular matrix (ECM) can be studied in a metastatic setting, we combined patient-derived CCA organoids (CCAOs) (n=3) with decellularized human lung (n=3) and decellularized human lymph node (n=13). Decellularization resulted in removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin. Proteomic analyses showed a tissue-specific ECM protein signature reflecting tissue functioning aspects. The macro and micro-scale mechanical properties, as determined by rheology and micro-indentation, revealed the local heterogeneity of the ECM. When growing CCAOs in decellularized lung and lymph nodes genes related to metastatic processes, including epithelial-to-mesenchymal transition and cancer stem cell plasticity, were significantly influenced by the ECM in an organ-specific manner. Furthermore, CCAOs exhibit significant differences in migration and proliferation dynamics dependent on the original patient tumor and donor of the target organ. In conclusion, CCA metastatic outgrowth is dictated both by the tumor itself as well as by the ECM of the target organ. Convergence of CCAOs with the ECM of its metastatic organs provide a new platform for mechanistic study of cancer metastasis.
Purinergic signaling: Diverse effects and therapeutic potential in cancer
Authors: Kaur Jasmeet , Dora Sanchit
Published: January 2023

Regardless of improved biological insights and therapeutic advances, cancer is consuming multiple lives worldwide. Cancer is a complex disease with diverse cellular, metabolic, and physiological parameters as its hallmarks. This instigates a need to uncover the latest therapeutic targets to advance the treatment of cancer patients. Purines are building blocks of nucleic acids but also function as metabolic intermediates and messengers, as part of a signaling pathway known as purinergic signaling. Purinergic signaling comprises primarily adenosine triphosphate (ATP) and adenosine (ADO), their analogous membrane receptors, and a set of ectonucleotidases, and has both short- and long-term (trophic) effects. Cells release ATP and ADO to modulate cellular function in an autocrine or paracrine manner by activating membrane-localized purinergic receptors (purinoceptors, P1 and P2). P1 receptors are selective for ADO and have four recognized subtypes—A1, A2A, A2B, and A3. Purines and pyrimidines activate P2 receptors, and the P2X subtype is ligand-gated ion channel receptors. P2X has seven subtypes (P2X1–7) and forms homo- and heterotrimers. The P2Y subtype is a G protein-coupled receptor with eight subtypes (P2Y1/2/4/6/11/12/13/14). ATP, its derivatives, and purinoceptors are widely distributed in all cell types for cellular communication, and any imbalance compromises the homeostasis of the cell. Neurotransmission, neuromodulation, and secretion employ fast purinergic signaling, while trophic purinergic signaling regulates cell metabolism, proliferation, differentiation, survival, migration, invasion, and immune response during tumor progression. Thus, purinergic signaling is a prospective therapeutic target in cancer and therapy resistance.
Case Report: Single-port laparoscopic total gastrectomy for gastric cancer in patient with situs inversus totalis
Authors: Lee In Young , Lee Danbi , Lee Chang Min
Published: January 2023

Situs inversus totalis (SIT) is a rare anatomical condition, where all the viscera appear in its reverse position. Although minimally invasive surgery has evolved to achieve totally laparoscopic gastrectomy for gastric cancer patients with SIT, it is difficult to perform lymphadenectomy in such a transposed anatomical condition. Recently, we performed a single-port laparoscopic total gastrectomy (SPTG) for gastric cancer in a patient with SIT. No postoperative complications or dietary problems were observed. Based on this experience, we are to design a safe strategy to perform D2 lymphadenectomy during SPTG in patients with SIT.
Limitations of radiosensitization by direct telomerase inhibition to treat high-risk medulloblastoma
Authors: Sengupta Satarupa , Senthil Kumar Shiva , Bondra Kathryn , Sobo Matthew , Mo Xiaokui , Drissi Rachid
Published: January 2023

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Previous studies have elucidated the genomic landscape of MB leading to the recognition of four core molecular subgroups (WNT, SHH, group 3 and group 4) with distinct clinical outcomes. Group 3 has the worst prognosis of all MB. Radiotherapy (RT) remains a major component in the treatment of poor prognosis MB but is rarely curative alone and is associated with acute and long-term toxicities. A hallmark of cancer cells is their unlimited proliferative potential which correlates closely with telomere length. The vast majority of malignant tumors activate telomerase to maintain telomere length, whereas this activity is barely detectable in most normal human somatic tissues, making telomerase inhibition a rational therapeutic target in the setting of cancer recurrence and therapy resistance. We and others have previously shown that short telomeres confer sensitivity to ionizing radiation (IR) suggesting that telomerase inhibition mediated telomere shortening will improve the efficacy of RT while minimizing its side effects. Here, we investigated the efficacy of the combination of IR with IMT, a potent telomerase inhibitor, in an in vivo model of group 3 MB. Our results indicate that although IMT inhibited MB telomerase activity resulting in telomere shortening and delayed tumor growth, the combination with IR did not prevent tumor recurrence and did not improve survival compared to the treatment with IR alone. Together, these findings suggest that the radiosensitization by direct telomerase inhibition is not an effective approach to treat high-risk pediatric brain tumors.
Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy
Authors: Wu Hao , Zhang Tianyi , Liu Qi , Wei Min , Li Yuping , Ma Qiang , Wang Lianhui , Zhu Yufu , Zhang Hengzhu
Published: January 2023

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).

Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.

Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p < 0.05).

Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.
Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR
Authors: Huangfu Yaru , Yu Xiuxian , Wan Chengyu , Zhu Yuda , Wei Zeliang , Li Fan , Wang Yilan , Zhang Kun , Li Shiyi , Dong Yuman , Li Yangying , Niu Hai , Xin Guang , Huang Wen
Published: January 2023

Severe acute pancreatitis (SAP) is a lethal gastrointestinal disorder, yet no specific and effective treatment is available. Its pathogenesis involves inflammatory cascade, oxidative stress, and autophagy dysfunction. Xanthohumol (Xn) displays various medicinal properties,

including anti-inflammation, antioxidative, and enhancing autophagic flux. However, it is unclear whether Xn inhibits SAP. This study investigated the efficacy of Xn on sodium taurocholate (NaT)-induced SAP (NaT-SAP) in vitro and in vivo. First, Xn attenuated biochemical and histopathological responses in NaT-SAP mice. And Xn reduced NaT-induced necrosis, inflammation, oxidative stress, and autophagy impairment. The mTOR activator MHY1485 and the AKT activator SC79 partly reversed the treatment effect of Xn. Overall, this is an innovative study to identify that Xn improved pancreatic injury by enhancing autophagic flux via inhibition of AKT/mTOR. Xn is expected to become a novel SAP therapeutic agent.
Rehabilitation assisted by Space technology—A SAHC approach in immobilized patients—A case of stroke
Authors: Kourtidou-Papadeli Chrysoula , Frantzidis Christos , Machairas Ilias , Giantsios Christos , Dermitzakis Emmanouil , Kantouris Nikolaos , Konstantinids Evdokimos , Bamidis Panagiotis , Vernikos Joan
Published: January 2023

Introduction: The idea behind the presentation of this case relates to utilizing space technology in earth applications with mutual benefit for both patients confined to bed and astronauts. Deconditioning and the progressiveness of skeletal muscle loss in the absence of adequate gravity stimulus have been of physiological concern. A robust countermeasure to muscle disuse is still a challenge for both immobilized patients and astronauts in long duration space missions. Researchers in the space medicine field concluded that artificial gravity (AG) produced by short-radius centrifugation on a passive movement therapy device, combined with exercise, has been a robust multi-system countermeasure as it re-introduces an acceleration field and gravity load.

Methods: A short-arm human centrifuge (SAHC) alone or combined with exercise was evaluated as a novel, artificial gravity device for an effective rehabilitation strategy in the case of a stroke patient with disability. The results reveal valuable information on an individualized rehabilitation strategy against physiological deconditioning. A 73-year-old woman was suddenly unable to speak, follow directions or move her left arm and leg. She could not walk, and self-care tasks required maximal assistance. Her condition was getting worse over the years, also she was receiving conventional rehabilitation treatment. Intermittent short-arm human centrifuge individualized protocols were applied for 5 months, three times a week, 60 treatments in total.

Results: It resulted in significant improvement in her gait, decreased atrophy with less spasticity on the left body side, and ability to walk at least 100 m with a cane. Balance and muscle strength were improved significantly. Cardiovascular parameters improved responding to adaptations to aerobic exercise. Electroencephalography (EEG) showed brain reorganization/plasticity evidenced through functional connectivity alterations and activation in the cortical regions, especially of the precentral and postcentral gyrus. Stroke immobility-related disability was also improved.

Discussion: These alterations were attributed to the short-arm human centrifuge intervention. This case study provides novel evidence supporting the use of the short-arm human centrifuge as a promising therapeutic strategy in patients with restricted mobility, with application to astronauts with long-term muscle disuse in space.
Relationship of strength, joint kinesthesia, and plantar tactile sensation to dynamic and static postural stability among patients with anterior cruciate ligament reconstruction
Authors: Hu Shanshan , Ma Xiaoli , Ma Xiaoyuan , Sun Wei , Zhou Zhipeng , Chen Yan , Song Qipeng
Published: January 2023

Objective: Postural stability is essential for high-level physical activities after anterior cruciate ligament reconstruction (ACLR). This study was conducted to investigate the relationship of muscle strength, joint kinesthesia, and plantar tactile sensation to dynamic and static postural stability among patients with anterior cruciate ligament reconstruction.

Methods: Forty-four patients over 6 months post anterior cruciate ligament reconstruction (age: 27.9 ± 6.8 years, height: 181.7 ± 8.7 cm, weight: 80.6 ± 9.4 kg, postoperative duration: 10.3 ± 3.6 months) participated in this study. Their static and dynamic postural stability, muscle strength, hamstring/quadriceps ratio, joint kinesthesia, and plantar tactile sensation were measured. Partial correlations were used to determine the correlation of the above-mentioned variables with time to stabilization (TTS) and root mean square of the center of pressure (COP-RMS) in anterior-posterior (AP) and mediolateral (ML) directions.

Results: Both TTSAP and TTSML were related to muscle strength and joint kinesthesia of knee flexion and extension; COP-RMSAP was correlated with plantar tactile sensations at great toe and arch, while COP-RMSML was correlated with joint kinesthesia of knee flexion, and plantar tactile sensation at great toe and heel. Dynamic stability was sequentially correlated with strength and joint kinesthesia, while static stability was sequentially correlated with plantar tactile sensation and joint kinesthesia.

Conclusion: Among patients with anterior cruciate ligament reconstruction, strength is related to dynamic postural stability, joint kinesthesia is related to dynamic and static postural stability, and plantar tactile sensation is related to static postural stability. Strength has a higher level of relationship to dynamic stability than joint kinesthesia, and plantar tactile sensation has a higher level of relationship to static stability than joint kinesthesia.
Rice immediately adapts the dynamics of photosynthates translocation to roots in response to changes in soil water environment
Authors: Miyoshi Yuta , Soma Fumiyuki , Yin Yong-Gen , Suzui Nobuo , Noda Yusaku , Enomoto Kazuyuki , Nagao Yuto , Yamaguchi Mitsutaka , Kawachi Naoki , Yoshida Eiji , Tashima Hideaki , Yamaya Taiga , Kuya Noriyuki , Teramoto Shota , Uga Yusaku
Published: January 2023

Rice is susceptible to abiotic stresses such as drought stress. To enhance drought resistance, elucidating the mechanisms by which rice plants adapt to intermittent drought stress that may occur in the field is an important requirement. Roots are directly exposed to changes in the soil water condition, and their responses to these environmental changes are driven by photosynthates. To visualize the distribution of photosynthates in the root system of rice plants under drought stress and recovery from drought stress, we combined X-ray computed tomography (CT) with open type positron emission tomography (OpenPET) and positron-emitting tracer imaging system (PETIS) with 11C tracer. The short half-life of 11C (20.39 min) allowed us to perform multiple experiments using the same plant, and thus photosynthate translocation was visualized as the same plant was subjected to drought stress and then re-irrigation for recovery. The results revealed that when soil is drier, 11C-photosynthates mainly translocated to the seminal roots, likely to promote elongation of the root with the aim of accessing water stored in the lower soil layers. The photosynthates translocation to seminal roots immediately stopped after rewatering then increased significantly in crown roots. We suggest that when rice plant experiencing drought is re-irrigated from the bottom of pot, the destination of 11C-photosynthates translocation immediately switches from seminal root to crown roots. We reveal that rice roots are responsive to changes in soil water conditions and that rice plants differentially adapts the dynamics of photosynthates translocation to crown roots and seminal roots depending on soil conditions.
Transcriptomic and metabolic regulatory network characterization of drought responses in tobacco
Authors: Hu Zhengrong , He Zexue , Li Yangyang , Wang Qing , Yi Pengfei , Yang Jiashuo , Yang Chenkai , Borovskii Gennadii , Cheng Xuejiao , Hu Risheng , Zhang Wenli
Published: January 2023

Drought stress usually causes huge economic losses for tobacco industries. Drought stress exhibits multifaceted impacts on tobacco systems through inducing changes at different levels, such as physiological and chemical changes, changes of gene transcription and metabolic changes. Understanding how plants respond and adapt to drought stress helps generate engineered plants with enhanced drought resistance. In this study, we conducted multiple time point-related physiological, biochemical,transcriptomic and metabolic assays using K326 and its derived mutant 28 (M28) with contrasting drought tolerance. Through integrative analyses of transcriptome and metabolome,we observed dramatic changes of gene expression and metabolic profiles between M28 and K326 before and after drought treatment. we found that some of DEGs function as key enzymes responsible for ABA biosynthesis and metabolic pathway, thereby mitigating impairment of drought stress through ABA signaling dependent pathways. Four DEGs were involved in nitrogen metabolism, leading to synthesis of glutamate (Glu) starting from NO−3 /NO−2 that serves as an indicator for stress responses. Importantly, through regulatory network analyses, we detected several drought induced TFs that regulate expression of genes responsible for ABA biosynthesis through network, indicating direct and indirect involvement of TFs in drought responses in tobacco. Thus, our study sheds some mechanistic insights into how plant responding to drought stress through transcriptomic and metabolic changes in tobacco. It also provides some key TF or non-TF gene candidates for engineering manipulation for breeding new tobacco varieties with enhanced drought tolerance.
Metabolic relay gene of aphid and primary symbiont as RNAi target loci for aphid control
Authors: Li Qian , Cheng Yu , Fan Jia , Chen Julian
Published: January 2023

Introduction

Aphids form a stable and mutually beneficial relationship with their primary symbiont Buchnera aphidicola, which play an important role in providing the missing nutrients to the host aphid. Based on the genome sequence of wheat aphid Siotobion miscanthi and its primary symbiont Buchnera that we obtained in our previously study, we identified a metabolic relay gene, ilvA, involved in the isoleucine synthesis pathway between aphids and Buchnera.

Method

In this study, we identified the location and sequence structure of ilvA gene in aphid genome, the expression level in different instars and tissues of aphids, and the effect of reducing ilvA expression on the growth and development of aphids by bioinformatics analysis, quantitative PCR, RNAi and bioassay experiments.

Result

Our study showed that ilvA was expressed at the highest level in the 2nd instar of the aphid, while the expression of this gene was significantly higher in the aphid bacteriocytes than in other tissues. Notably, this gene is localized on the aphid sex chromosome and remains highly conserved and collinearity across different aphid genomes. Knocking down the expression of ilvA reduced the aphid body weight and production. However, the indices of mortality decreased slightly, but were not significantly different, compared to the control.

Discussion

The results show that the relay genes between aphids and their symbionts in the metabolism of essential nutrients have potential roles in the growth and development of aphids, meanwhile, providing target loci and new ideas for RNAi-based aphid green control strategies.
Distinct leaf functional traits of Tamarix chinensis at different habitats in the hinterland of the Taklimakan desert
Authors: Tayir Mawlida , Dai Yue , Shi Qingdong , Abdureyim Anwar , Erkin Flora , Huang Wanyuan
Published: January 2023

Leaf functional traits reflect plant adaptive strategies towards environmental heterogeneity. However, which factor play the key role of plasticity of leaf functional traits among various variable environmental factors remains unclear in desert hinterland oasis area. Here, we analyzed variations in leaf water content (LWC), δ13C values of leaves (δ13C), specific leaf area (SLA), leaf organic carbon concentration (LOC), leaf total nitrogen concentration (LTN), leaf total phosphorus concentration (LTP), and leaf C: N: P stoichiometry in Tamarix chinensis growing in five habitats at the Daliyabuyi, a natural pristine oasis in northwestern China, that differ abiotically and biotically. The spatial heterogeneity of leaf functional traits was evident. Abiotic factors vitally influence leaf functional traits, of which groundwater depth (GWD) and soil C: N stoichiometry (SOC: STN) are crucial. GWD exhibited close relationships with LWC (P < 0.05) and LOC: LTP (P < 0.01), but not δ13C. Soil water content (SWC) and SOC: STN were negatively related to SLA (P < 0.01; P < 0.05). While, SOC: STN showed positive relationships with LOC: LTN (P < 0.05). As for biological factors, we found T. chinensis in habitat with Sophora alopecuroidies had the highest LTN, possibly as a result of N fixation of leguminous plants (S. alopecuroidies) promotes the N concentration of T. chinensis. Close relationships also existed between leaf functional traits, LWC showed significantly negatively relatd to δ13C, LOC: LTN and LOC: LTP (P < 0.05), whereas δ13C had positively correlated with LOC: LTN (P < 0.01) but negatively correlated with LTN (P < 0.05). T. chinensis had relative higher LWC couple with lower δ13C, and exhibiting lower C, N, P in leaves and their stoichiometric ratios, and also lower SLA which compared with other terrestrial plant. Such coordinations suggesting that T. chinensis develops a suite of trait combinations mainly tends to more conservative to response local habitats in Daliyabuyi, which is contribute to understand desert plant resource acquisition and utilization mechanisms in extremely arid and barren environments.
The binding pocket properties were fundamental to functional diversification of the GDSL-type esterases/lipases gene family in cotton
Authors: Wang Jianshe , Zhao Haiyan , Qu Yunfang , Yang Peng , Huang Jinling
Published: January 2023

Cotton is one of the most important crops in the world. GDSL-type esterases/lipases (GELPs) are widely present in all kingdoms and play an essential role in regulating plant growth, development, and responses to abiotic and biotic stresses. However, the molecular mechanisms underlying this functional diversity remain unclear. Here, based on the identification of the GELP gene family, we applied genetic evolution and molecular simulation techniques to explore molecular mechanisms in cotton species. A total of 1502 GELP genes were identified in 10 cotton species. Segmental duplication and differences in evolutionary rates are the leading causes of the increase in the number and diversity of GELP genes during evolution for ecological adaptation. Structural analysis revealed that the GELP family has high structural diversity. Moreover, molecular simulation studies have demonstrated significant differences in the properties of the binding pockets among cotton GELPs. In the process of adapting to the environment, GELPs not only have segmental duplication but also have different evolutionary rates, resulting in gene diversity. This diversity leads to significant differences in the 3D structure and binding pocket properties and, finally, to functional diversity. These findings provide a reference for further functional analyses of plant GELPs.
Towards greenhouse cultivation of Artemisia annua: The application of LEDs in regulating plant growth and secondary metabolism
Authors: Zhang Ningyi , Yang Haohong , Han Tianqi , Kim Hyoung Seok , Marcelis Leo F. M.
Published: January 2023

Artemisinin is a sesquiterpene lactone produced in glandular trichomes of Artemisia annua, and is extensively used in the treatment of malaria. Growth and secondary metabolism of A. annua are strongly regulated by environmental conditions, causing unstable supply and quality of raw materials from field grown plants. This study aimed to bring A. annua into greenhouse cultivation and to increase artemisinin production by manipulating greenhouse light environment using LEDs. A. annua plants were grown in a greenhouse compartment for five weeks in vegetative stage with either supplemental photosynthetically active radiation (PAR) (blue, green, red or white) or supplemental radiation outside PAR wavelength (far-red, UV-B or both). The colour of supplemental PAR hardly affected plant morphology and biomass, except that supplemental green decreased plant biomass by 15% (both fresh and dry mass) compared to supplemental white. Supplemental far-red increased final plant height by 23% whereas it decreased leaf area, plant fresh and dry weight by 30%, 17% and 7%, respectively, compared to the treatment without supplemental radiation. Supplemental UV-B decreased plant leaf area and dry weight (both by 7%). Interestingly, supplemental green and UV-B increased leaf glandular trichome density by 11% and 9%, respectively. However, concentrations of artemisinin, arteannuin B, dihydroartemisinic acid and artemisinic acid only exhibited marginal differences between the light treatments. There were no interactive effects of far-red and UV-B on plant biomass, morphology, trichome density and secondary metabolite concentrations. Our results illustrate the potential of applying light treatments in greenhouse production of A. annua to increase trichome density in vegetative stage. However, the trade-off between light effects on plant growth and trichome initiation needs to be considered. Moreover, the underlying mechanisms of light spectrum regulation on artemisinin biosynthesis need further clarification to enhance artemisinin yield in greenhouse production of A. annua.
Integration of high-throughput omics technologies in medicinal plant research: The new era of natural drug discovery
Authors: Zhang Wenting , Zeng Yuan , Jiao Meng , Ye Chanjuan , Li Yanrong , Liu Chuanguang , Wang Jihua
Published: January 2023

Medicinal plants are natural sources to unravel novel bioactive compounds to satisfy human pharmacological potentials. The world’s demand for herbal medicines is increasing year by year; however, large-scale production of medicinal plants and their derivatives is still limited. The rapid development of modern technology has stimulated multi-omics research in medicinal plants, leading to a series of breakthroughs on key genes, metabolites, enzymes involved in biosynthesis and regulation of active compounds. Here, we summarize the latest research progress on the molecular intricacy of medicinal plants, including the comparison of genomics to demonstrate variation and evolution among species, the application of transcriptomics, proteomics and metabolomics to explore dynamic changes of molecular compounds, and the utilization of potential resources for natural drug discovery. These multi-omics research provide the theoretical basis for environmental adaptation of medicinal plants and allow us to understand the chemical diversity and composition of bioactive compounds. Many medicinal herbs’ phytochemical constituents and their potential health benefits are not fully explored. Given their large diversity and global distribution as well as the impacts of growth duration and environmental factors on bioactive phytochemicals in medicinal plants, it is crucial to emphasize the research needs of using multi-omics technologies to address basic and applied problems in medicinal plants to aid in developing new and improved medicinal plant resources and discovering novel medicinal ingredients.
A high-throughput yeast approach to characterize aquaporin permeabilities: Profiling the Arabidopsis PIP aquaporin sub-family
Authors: Groszmann Michael , De Rosa Annamaria , Chen Weihua , Qiu Jiaen , McGaughey Samantha A. , Byrt Caitlin S. , Evans John R.
Published: January 2023

Introduction

Engineering membrane transporters to achieve desired functionality is reliant on availability of experimental data informing structure-function relationships and intelligent design. Plant aquaporin (AQP) isoforms are capable of transporting diverse substrates such as signaling molecules, nutrients, metalloids, and gases, as well as water. AQPs can act as multifunctional channels and their transport function is reliant on many factors, with few studies having assessed transport function of specific isoforms for multiple substrates.

Methods

High-throughput yeast assays were developed to screen for transport function of plant AQPs, providing a platform for fast data generation and cataloguing of substrate transport profiles. We applied our high-throughput growth-based yeast assays to screen all 13 Arabidopsis PIPs (AtPIPs) for transport of water and several neutral solutes: hydrogen peroxide (H2O2), boric acid (BA), and urea. Sodium (Na+) transport was assessed using elemental analysis techniques.

Results

All AtPIPs facilitated water and H2O2 transport, although their growth phenotypes varied, and none were candidates for urea transport. For BA and Na+ transport, AtPIP2;2 and AtPIP2;7 were the top candidates, with yeast expressing these isoforms having the most pronounced toxicity response to BA exposure and accumulating the highest amounts of Na+. Linking putative AtPIP isoform substrate transport profiles with phylogenetics and gene expression data, enabled us to align possible substrate preferences with known and hypothesized biological roles of AtPIPs.

Discussion

This testing framework enables efficient cataloguing of putative transport functionality of diverse AQPs at a scale that can help accelerate our understanding of AQP biology through big data approaches (e.g. association studies). The principles of the individual assays could be further adapted to test additional substrates. Data generated from this framework could inform future testing of AQP physiological roles, and address knowledge gaps in structure-function relationships to improve engineering efforts.
Prefabricated platinum nanomaterial matrix for MALDI-MS imaging of oligosaccharides and lipids in plant tissues
Authors: Shen Yu-Lin , Zhuang Si-Jia , Yang Fan , Gong Can , Xu Xu
Published: January 2023

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) can visualize the spatial distribution characteristics of molecules in tissues in situ, in which the matrix plays a key role. In this paper, we propose a platinum nanomaterial pre-coated matrix, which can be prepared in bulk by sputtering platinum nanoparticles onto slides using an ion sputterer and then used for MALDI-MS analysis by placing tissue sections on the matrix. We used this matrix for MALDI-MS imaging analysis of corn kernels and germinated wheat sections, and the results show that triacylglycerides were mainly distributed in the embryo of corn kernels and germinated wheat, and sugars were mainly distributed in the endosperm, with the highest content of disaccharides.It provides a simple and reliable experimental condition for analyzing the distribution of oligosaccharide and lipid components in plant tissues.
Perceived usefulness of open educational resources: Impact of switching to online learning for face-to-face and distance learners
Authors: Cheung Simon K. S. , Wong Billy T. M. , Li Kam Cheong
Published: January 2023

This paper reports a study on the perceived usefulness of university students on open educational resources (OER) in relation to the switch of learning mode to online learning during the COVID-19 pandemic. The participants involved two groups of students, one studying in a face-to-face mode and the other in a distance learning mode. They took part in a survey which was conducted in 2019 before the pandemic (with a total of 912 responses) and 2021 during the pandemic (with a total of 1,018 responses). The results show that both groups of students generally perceived OER to be more useful during the pandemic. The specific types of OER which were perceived as relatively more useful include open online courses and open access textbooks. Face-to-face students showed a higher level of perceived usefulness of OER for preparing tests and examinations, while distance learning students perceived OER as more useful for supplementing course materials. They both concerned about the limitations of OER, especially on accuracy and comprehensiveness. The findings suggest the importance of recognizing the diverse needs of the two groups of students and offering appropriate OER support for them.