Base-Mediated Cascade Lactonization/1,3-Dipolar Cycloaddition Pathway for the One-Pot Assembly of Coumarin-Functionalized Pyrrolo[2,1-a]isoquinolines.

An elegant and highly concise strategy for the construction of coumarin-functionalized pyrrolo[2,1-a]isoquinolines from available propargylamines and isoquinolinium N-ylides has been disclosed. In this reaction, isoquinolinium N-ylides acted as a C2 synthon to form a coumarin ring as well as a 1,3-dipole to construct a pyrrole ring in a single pot. This cascade process involves 1,4-conjugate addition/lactonization/1,3-dipolar cycloaddition to construct four chemical bonds (one C-O bond and three C-C bonds) and two new heterocyclic skeletons. Additionally, most of these compounds showed good fluorescence properties and exhibited high molar extinction coefficient and large Stokes shifts.

Bombyx mori UFL1 facilitates BmNPV proliferation by regulating host cell apoptosis through PERK.

Ubiquitin-fold modifier 1 (UFM1) is attached to protein substrates through the sequential activity of an E1 (UBA5)-E2 (UFC1)-E3 (UFL1) cascade. UFL1 is the E3 ligase for UFMylation in vertebrates. However, there have been no studies on UFL1 in silkworm to date. In this study, we identified a UFL1 ortholog in Bombyx mori genome. Spatio-temporal expression profiles showed that BmUFL1 expression was high in the midgut, epidermis, and testis and in the pupa-adult stage. BmUFL1 knockdown inhibited B. mori nucleopolyhedrovirus (BmNPV) proliferation, while BmUFL1 overexpression promoted BmNPV proliferation. Mechanically, protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling and cell apoptosis are involved in BmUFL1-regulated BmNPV proliferation. Overall, these results suggest that BmUFL1 facilitates BmNPV proliferation in silkworm.

Intramedullary administration of tranexamic acid reduces bleeding in proximal femoral nail antirotation surgery for intertrochanteric fractures in elderly individuals: A randomized controlled trial.

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67 % in the TXA group and 47.95 % in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION: We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.

Tuning Shortwave-Infrared J-aggregates of Aromatic Ring-Fused Aza-BODIPYs by Peripheral Substituents for Combined Photothermal and Photodynamic Therapies at Ultralow Laser Power.

Achieving photothermal therapy (PTT) at ultralow laser power density is crucial for minimizing photo-damage and allowing for higher maximum permissible skin exposure. However, this requires photothermal agents to possess not just superior photothermal conversion efficiency (PCE), but also exceptional near-infrared (NIR) absorptivity. J-aggregates, exhibit a significant redshift and narrower absorption peak with a higher extinction coefficient. Nevertheless, achieving predictable J-aggregates through molecular design remains a challenge. In this study, we successfully induced desirable J-aggregation (λabs max : 968 nm, ϵ: 2.96×105  M-1 cm-1 , λem max : 972 nm, ΦFL : 6.2 %) by tuning electrostatic interactions between π-conjugated molecular planes through manipulating molecular surface electrostatic potential of aromatic ring-fused aza-BODIPY dyes. Notably, by controlling the preparation method for encapsulating dyes into F-127 polymer, we were able to selectively generate H-/J-aggregates, respectively. Furthermore, the J-aggregates exhibited two controllable morphologies: nanospheres and nanowires. Importantly, the shortwave-infrared J-aggregated nanoparticles with impressive PCE of 72.9 % effectively destroyed cancer cells and mice-tumors at an ultralow power density of 0.27 W cm-2 (915 nm). This phototherapeutic nano-platform, which generates predictable J-aggregation behavior, and can controllably form J-/H-aggregates and selectable J-aggregate morphology, is a valuable paradigm for developing photothermal agents for tumor-treatment at ultralow laser power density.

Characterization of a silkworm UFM1 homolog in regulating Bombyx mori unfolded protein response and nucleopolyhedrovirus replication.

The Ubiquitin (Ub)-like molecules is essential for animal development and the physiopathology of multiple tissues in the vertebrate. Ubiquitin-fold modifier 1 (UFM1) is one of the newly-identified UBL, which is covalently attached to its substrates through the orchestrated action of a dedicated enzymatic cascade. Bombyx mori nuclear polyhedrosis virus (BmNPV) is one of the main pathogens in sericulture, causing serious economic losses every year. However, there are no studies on UFMylation and the effect of UFMylation on BmNPV replication in silkworm. In this study, we identified BmUFM1 in the B. mori genome. Spatio-Temporal expression profiles showed that BmUFM1 expression was highly in hemocytes and response to various pathogenic stimuli. Furthermore, BmUFM1 is involved in the regulation of ER stress induced Unfolded Protein Response (UPR) and knockdown of BmUFM1 inhibited BmNPV replication. Overall, these results suggest that BmUFM1 plays an important role in facilitating BmNPV proliferation in silkworm. Our findings advance the understanding of UFM1's conjugation machinery, and also provides a potentially molecular target for BmNPV prevention and silkworm breeding.

Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells.

Adoptive cell therapy (ACT) with expanded tumor-infiltrating lymphocytes (TIL) or TCR gene-modified T cells (TCR-T) that recognize mutant KRAS neo-antigens can mediate tumor regression in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (Tran et al in N Engl J Med, 375:2255-2262, 2016; Leidner et al in N Engl J Med, 386:2112-2119, 2022). The mutant KRAS-targeted ACT holds great potential to achieve durable clinical responses for PDAC, which has had no meaningful improvement over 40 years. However, the wide application of mutant KRAS-centric ACT is currently limited by the rarity of TIL that recognize the mutant KRAS. In addition, PDAC is generally recognized as a poorly immunogenic tumor, and TILs in PDAC are less abundant than in immunogenic tumors such as melanoma. To increase the success rate of TIL production, we adopted a well-utilized K562-based artificial APC (aAPC) that expresses 4-1BBL as the costimulatory molecules to enhance the TIL production from PDCA. However, stimulation with K562-based aAPC led to a rapid loss of specificity to mutant KRAS. To selectively expand neo-antigen-specific T cells, particularly mKRAS, from the TILs, we used tandem mini gene-modified autologous T cells (TMG-T) as the novel aAPC. Using this modified IVS protocol, we successfully generated TIL cultures specifically reactive to mKRAS (G12V). We believe that autologous TMG-T cells provide a reliable source of autologous APC to expand a rare population of neoantigen-specific T cells in TILs.

Thermoreversible Tissue Adhesion with Hydrogel Through a Topological Entanglement Approach.

Achieving thermoreversible adhesion between hydrogel and living tissues in a facile way is challenging. Existing strategies bring difficulty to the chemical design and synthesis of hydrogels. Herein, an approach to achieve tough thermoreversible tissue adhesion with hydrogel is proposed, which uses a polymer solution with heat-induced sol-gel transition as the interfacial polymer matrix, with no chemical design required for the hydrogel network. When the interfacial polymer matrix is introduced to the interface of the hydrogel and living tissues, it can gelate in situ within the substrate networks under a temperature stimulus, and topologically entangle with the preexisting networks of the substrates, which generates a strong adhesion. By triggering with another temperature stimulus, the newly formed network dissociates to realize an easy detachment. Thermoreversible adhesion is demonstrated between polyacrylamide hydrogel and various porcine tissues as examples, and the mechanism of this adhesion strategy is studied by varying various influence factors. A theoretical model that can fit and predict the effects of different parameters on the adhesion energies is also established. This adhesion strategy based on topological entanglement among a thermoreversible polymer system and the substrates may broaden the achieving methods of thermoreversible tissue adhesion.

Multimodal ultrasound features of breast cancers: correlation with molecular subtypes.

OBJECTIVES: To investigate whether multimodal intratumour and peritumour ultrasound features correlate with specific breast cancer molecular subtypes. METHODS: From March to November 2021, a total of 85 patients with histologically proven breast cancer underwent B-mode, real-time elastography (RTE), colour Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The time intensity curve (TIC) of CEUS was obtained, and the peak and time to peak (TTP) were analysed. Chi-square and binary logistic regression were used to analyse the connection between multimodal ultrasound imaging features and breast cancer molecular subtype. RESULTS: Among 85 breast cancers, the subtypes were as follows: luminal A (36 cases, 42.4%), luminal B (20 cases, 23.5%), human epidermal growth factor receptor-2 positive (HER2+) (16 cases, 18.8%), and triple negative breast cancer (TNBC) (13 cases, 15.3%). Binary logistic regression models showed that RTE (P < 0.001) and CDFI (P = 0.036) were associated with the luminal A cancer subtype (C-index: 0.741), RTE (P = 0.016) and the peak ratio between intratumour and corpus mamma (P = 0.036) were related to the luminal B cancer subtype (C-index: 0.788). The peak ratio between peritumour and intratumour (P = 0.039) was related to the HER2 + cancer subtype (C-index: 0.859), and CDFI (P = 0.002) was associated with the TNBC subtype (C-index: 0.847). CONCLUSIONS: Multimodal ultrasound features could be powerful predictors of specific breast cancer molecular subtypes. The intra- and peritumour CEUS features play assignable roles in separating luminal B and HER2 + breast cancer subtypes.

Clinical applications of the mastoid emissary vein.

PURPOSE: During retrosigmoid craniotomy, the mastoid emissary vein (MEV) can be a source of considerable bleeding during the operation, especially when the larger diameter MEV or sigmoid sinus is torn. In this study, we evaluated the relevant structure of the MEV for their anatomy and applied the data in surgery to summarize their clinical significance. METHODS: The posterior craniocervical regions of 15 silicon-injected Chinese human cadaver specimens were dissected to expose the MEV and adjacent structures. Fifty-one patients who were scheduled to undergo retrosigmoid craniotomy were selected. All patients underwent preoperative routine CT of the head. The relevant data were collected on cadaveric anatomy and CT. Eventually, all patients underwent retrosigmoid craniotomy and the MEV was observed during the operation. RESULTS: In cadaver specimens, the prevalence of the MEV was 90.0%. It originated from the middle and lower parts of the posterior wall of the sigmoid sinus and extended in the posterior direction in the mastoid process, usually having 1-2 external openings (86.7%) and only 1 internal opening. The intraosseous courses of the MEV were classified as straight and curved. The straight type accounted for 57.9%, and the curved type for 42.1%. The mean diameter of the MEV was 1.84 ± 0.85 mm, and the straight length of the MEV inside the mastoid process was 11.93 ± 3.58 mm. In 16.7% and 6.7% of all cadaver specimens, the MEV diameter was greater than 2.5 and 4 mm, respectively. In 51 patients (bilateral), routine head CT scan showed the MEV in 49.0% of the patients, and the MEV diameter was greater than 2.5 and 4 mm, respectively, in 17.6% (18/102) and 3.9% (4/102) of the cases. During surgery (unilateral) in the 51 patients, 48 had the MEV and 3 had no MEV. None of the patients had sigmoid sinus tears or massive bleeding. CONCLUSION: In the process of retrosigmoid craniotomy, detailed anatomical knowledge of the MEV, well-planned CT scan, and meticulous microsurgical techniques are key for successful operation, which can reduce the occurrence of complications.

A clinical report of intracranial granulocytic sarcoma and a literature review.

BACKGROUND: Granulocytic sarcoma (GS), is also referred to as myeloid sarcoma. It is a solid mass formed by the primitive or immature myeloid cells extramedullary infiltration, which is commonly caused by acute myelogenous leukemia (AML) or chronic myelogenous leukemia (CML). It mainly involves bones, lymph nodes, skin and soft tissues of the head and neck. In general, the incidence is low and central nervous system (CNS) involvement is relatively rare. The clinical manifestations of the disease are varied and the treatment is intractable. CASE DESCRIPTION: A 53-year-old male with intracranial granulocytic sarcoma who suffered a pressing pain on the left cheek. The patient had a hypophasis with left corneal reflex diminished. He had bilateral anisocoria, lower jaw and tongue tilted to the left upon opening the mouth and the left pharyngeal reflex was declined. The whole blood routine was normal except for eosinophils, head magnetic resonance imaging plain scan revealed a space-occupying lesion. Postoperative pathology suggested GS. Unfortunately, the disease progressed quickly and the patient died. CONCLUSION: Isolated GS is often difficult to diagnose accurately. The patient's medical history should be carefully reviewed, all relevant tests should be performed, and various differential diagnoses should be familiarized with to improve the accuracy of diagnosis. And on this basis, to develop a personalized treatment plan for different patients.

De-differentiation associated with drop metastasis of a recurrent intracranial solitary fibrous tumor: a case report and literature review.

BACKGROUND: Central nervous system is a rare occurring location of solitary fibrous tumors (SFTs). SFTs have a potential for recurrence, which is the leading cause of death in patients with these disease entities. De-differentiation phenomenon combined with cerebrospinal fluid (CSF) dissemination through drop metastasis of STFs from intracranial to intraspinal has only been reported in extremely limited cases. CASE DESCRIPTION: Herein, we present a case of SFT in a 54-year old male. MRI showed characteristic of mixed high and low signal with 6.3 cm × 6.5 cm × 5.9 cm. After radical surgical resection, the pathology indicated benign SFT. However, MRI re-examination of 22 months later detected local recurrence, concomitant with spreading of intracranial and intraspinal through CSF dissemination. And interestingly, the second pathology found de-differentiation phenomenon and malignance of SFT, in which some areas transformed to rhabdomyosarcoma. CONCLUSION: This is the first case report of recurrent intracranial SFT de-differentiating to rhabdomyosarcoma concurrent with CSF pathway drop metastasis. Benign intracranial SFTs have the potential of de-differentiation, which may play an important role in its distant metastasis. The underlying molecular biological and pathological mechanisms of benign SFT malignance transformation still warrant further exploration.

Improving medical student recruitment into neurosurgery through teaching reform.

OBJECTIVE: This study aimed to determine whether a combination of case-based learning (CBL) and problem-based learning (PBL) methods in teaching can improve the academic performance and recruitment of medical students for neurosurgery. METHODS: Four classes of fourth-year medical students were randomly divided into two groups. The traditional model group received the traditional teaching method, and the CBL-PBL group received the combined teaching methods of CBL and PBL. After the courses, the differences between the two groups in self-perceived competence, satisfaction with the course, post-class test scores, and clinical practice abilities were compared, and the proportions of neurosurgery major selection in pre- and post-curriculum between the two groups were also analyzed. RESULTS: Self-perceived competence, post-class test scores, and clinical practice abilities in the CBL-PBL group were better than those in the traditional model group. The students in the CBL-PBL group showed a higher degree of satisfaction with the course than those in the traditional model group (χ2 = 12.03, P = 0.007). At the end of the semester, the proportion of students who chose neurosurgery majors in the CBL-PBL group was 13.3%, more than the 3.4% in the traditional model group (χ2 = 3.93, P = 0.048). CONCLUSION: Compared with the traditional teaching method, the CBL and PBL integrated method is more effective for improving the performance of medical students and enhancing their clinical capabilities in neurosurgery teaching. The CBL-PBL method effectively improved students' interests in neurosurgery, potentially contributing to increasing medical student recruitment into neurosurgery.

Light-induced HY5 Functions as a Systemic Signal to Coordinate the Photoprotective Response to Light Fluctuation.

Optimizing the photoprotection of different leaves as a whole is important for plants to adapt to fluctuations in ambient light conditions. However, the molecular basis of this leaf-to-leaf communication is poorly understood. Here, we used a range of techniques, including grafting, chlorophyll fluorescence, revers transcription quantitative PCR, immunoblotting, chromatin immunoprecipitation, and electrophoretic mobility shift assays, to explore the complexities of leaf-to-leaf light signal transmission and activation of the photoprotective response to light fluctuation in tomato (Solanum lycopersicum). We established that light perception in the top leaves attenuated the photoinhibition of both PSII and PSI by triggering photoprotection pathways in the bottom leaves. Local light promoted the accumulation and movement of LONG HYPOCOTYL5 from the sunlit local leaves to the systemic leaves, priming the photoprotective response of the latter to light fluctuation. By directly activating the transcription of PROTON GRADIENT REGULATION5 and VIOLAXANTHIN DE-EPOXIDASE, LONG HYPOCOTYL5 induced cyclic electron flow, the xanthophyll cycle, and energy-dependent quenching. Our findings reveal a systemic signaling pathway and provide insight into an elaborate regulatory network, demonstrating a pre-emptive advantage in terms of the activation of photoprotection and, hence, the ability to survive in a fluctuating light environment.

FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. Thus, the present study was designed to evaluate the effects of the S1PR1 modulator FTY720 on neurovascular unit (NVU) after experimental TBI in mice. The weight-drop TBI method was used to induce TBI. Western blot (WB) was performed to determine the levels of SIPR1, claudin-5 and occludin at different time points. FTY720 was intraperitoneally administered to mice after TBI was induced. The terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay was used to assess endothelial cell apoptosis. Immunofluorescence and WB were performed to measure the expression of tight junction proteins: claudin-5 and occludin. Evans blue (EB) permeability assay and brain water content were applied to evaluate the blood-brain barrier (BBB) permeability and brain edema. Immunohistochemistry was performed to assess the activation of astrocytes and microglia. The results showed that FTY720 administration reduced endothelial cell apoptosis and improved BBB permeability. FTY720 also attenuated astrocytes and microglia activation. Furthermore, treatment with FTY720 not only improved neurological function, but also increased the survival rate of mice significantly. These findings suggest that FTY720 administration restored the structure of the NVU after experimental TBI by decreasing endothelial cell apoptosis and attenuating the activation of astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing the activation of microglia in TBI mice.

Spontaneous acute epidural hematoma associated with chronic subdural hematoma due to dural metastasis of gastric carcinoma: a case report and literature review.

Background: Non-traumatic spontaneous acute epidural hematoma (EDH) happening to chronic subdural hematoma (SDH) caused by dural metastases is a rare entity. Pathogenesis can be derived from infection, coagulopathy, and inflammation. Malignant tumors metastasize to dura mater is one of the most infrequent causes. The exact mechanism remains elusive in spite of several possible speculations. The clinical manifestations, management and outcomes vary among reported cases.Case Description: A 45-year-old woman without history of trauma presented with headache, vomiting and disturbance of consciousness and developed brain hernia rapidly. On arival, she has lost into coma with Glasgow coma scale (GCS) score 5, bilateral pupils were not equal, with disappeared reflectance. Emergency imaging prompted large acute EDH, combined with SDH, arising from dural granular neoplasm confirmed intraoperatively. Four days after surgery, the bilateral pupils were equal in size and sensitive to light reflection.Conclusion: Dural metastases can cause EDH, chronic SDH can also be resulted from metastatic tumors of dura mater. When dealing with spontaneous non-traumatic hematoma around the dura mater, to make the precise diagnosis is sometimes doubtful and confusing. The stream of diagnostic thinking should be opened, including medical diseases such as liver and kidney disease, drug history, history of cancer and other possible clues. Thus, a detailed and purposeful systematic medical history review and physical examination is important in order to make more appropriate strategies for the clinic.

Intracranial solitary fibrous tumor/hemangiopericytomas: a clinical analysis of a series of 17 patients.

OBJECTIVE: Solitary fibrous tumors (SFTs) and haemangiopericytomas (HPCs) are rare mesenchymal tumors in central nervous system (CNS). Although progressed recognition to the diagnosis and treatment of SFT/HPCs, it still remains many confusions regarding on its occurrence, aggressive evolution, malignant transformation, dedifferentiation phenomenon, distant metastasis and unpredictable propensity. PATIENTS AND METHODS: Seventeen cases of CNS SFT/HPCs who underwent surgical treatment from January 2010 to December 2020 were collected in the authors' institute. Clinical, radiological, pathological data and followup details were reviewed in all cases. RESULTS: The age of this series was 41-73 years old. Seven cases located subtentorially, five cases originated from middle skull base and four in supratentorial. MRI shows iso-signal intensity on T1WI, and heterogeneous slightly long/short signal on T2WI. There is significant contrast after gadolinium-enhancement. It is easy to be misdiagnosed before surgery. The positive rate of nuclear STAT6 is 94.12%, higher than CD34 (87.5%). Eight patients were grade I, eight grade II and one in grade III. Five cases developed tumor relapse, in which two cases had local intracranial recurrence combined with dissemination and metastasis of cerebrospinal fluid in the spinal canal, accompanied by pathological malignant transformation, and another one occurred blood metastasis. CONCLUSIONS: CNS SFT/HPCs are rare intracranial tumors with unpredictable propensity. Gross total resection is critical to its overall clinical prognosis. Given its potential recurrence and malignant transition, adjuvant radiotherapies are recommended when necessary, and long-term follow-up is indispensable. The underlying molecular biological mechanisms are still needed to be further exploration.

TNF-α-induced p53 activation induces apoptosis in neurological injury.

It was previously confirmed that the apoptotic and necrotic neurons are found during the acute post-traumatic period, suggesting the induction of apoptosis after traumatic brain injury (TBI). To further explore the involvement of apoptotic factors in TBI, an apoptosis antibody array was conducted to measure the alterations of apoptotic factors in rat brain cortex after TBI. As a result, the Neurological Severity Scale (NSS) scores after TBI were increased, and the cell morphology of the brain cortex was destructed with increased neuronal apoptosis. Furthermore, the caspase-3 activity was increased, and the apoptotic-related factors TNF-α and p53 were up-regulated in the brain cortex. More importantly, in vitro experiments demonstrated that down-regulation of TNF-α in oxygen-glucose deprivation/reoxygenation (OGD/R) cells increased cell viability and decreased apoptosis and the p53 expression. These results suggested the involvement of TNF-α-induced apoptotic signalling pathway by activating p53 in the molecular mechanism of neurological injury.

Crosstalk of PIF4 and DELLA modulates CBF transcript and hormone homeostasis in cold response in tomato.

The ability to interpret daily and seasonal fluctuations, latitudinal and vegetation canopy variations in light and temperature signals is essential for plant survival. However, the precise molecular mechanisms transducing the signals from light and temperature perception to maintain plant growth and adaptation remain elusive. We show that far-red light induces PHYTOCHROME-INTERACTING TRANSCRIPTION 4 (SlPIF4) accumulation under low-temperature conditions via phytochrome A in Solanum lycopersicum (tomato). Reverse genetic approaches revealed that knocking out SlPIF4 increases cold susceptibility, while overexpressing SlPIF4 enhances cold tolerance in tomato plants. SlPIF4 not only directly binds to the promoters of the C-REPEAT BINDING FACTOR (SlCBF) genes and activates their expression but also regulates plant hormone biosynthesis and signals, including abscisic acid, jasmonate and gibberellin (GA), in response to low temperature. Moreover, SlPIF4 directly activates the SlDELLA gene (GA-INSENSITIVE 4, SlGAI4) under cold stress, and SlGAI4 positively regulates cold tolerance. Additionally, SlGAI4 represses accumulation of the SlPIF4 protein, thus forming multiple coherent feed-forward loops. Our results reveal that plants integrate light and temperature signals to better adapt to cold stress through shared hormone pathways and transcriptional regulators, which may provide a comprehensive understanding of plant growth and survival in a changing environment.

The HY5 and MYB15 transcription factors positively regulate cold tolerance in tomato via the CBF pathway.

The induction of C-repeat binding factors (CBFs) is crucial for plant survival at low temperatures. Therefore, understanding the mechanisms that regulate CBF transcription is vital for the future development of crops with increased cold tolerance. Here, we provide evidence for the existence of a LONG HYPOCOTYL 5 (HY5)-MYB15-CBFs transcriptional cascade that plays a crucial role in the cold response in tomato. The exposure of tomato plants to cold (4°C) increased the levels of HY5, MYB15 and CBFs transcripts. Moreover, mutations in HY5 or MYB15 decreased the levels of CBF transcripts. In contrast, overexpression of HY5 or MYB15 increased CBF transcript abundance. Crucially, the HY5 transcription factor activated the expression of MYB15 by directly binding to the promoter region, while both HY5 and MYB15 activated the expression of CBF1, CBF2 and CBF3. Taken together, these data show that HY5 can directly regulate CBF transcript levels, and also influence CBF expression indirectly via MYB15. The coordinated action of HY5 and MYB15 allows precise regulation of CBF expression and subsequent cold tolerance. These findings provide an improved understanding of the molecular mechanisms affording transcriptional regulation of CBFs, which can be exploited in the future to enhance cold tolerance in crops.

The anatomy of the parapharyngeal segment of the internal carotid artery for endoscopic endonasal approach.

Injury to the internal carotid artery (ICA) is a life-threatening complication of endoscopic endonasal approaches. The objective of this study is to illustrate the detail anatomy of the parapharyngeal segment of the ICA (PPICA) to safe endoscopic endonasal surgery. The anatomical dissection was performed in 10 cadaveric specimens and several crucial anatomical landmarks were identified and measured. In addition, 50 dry skulls were studied to further assess the relationship between the pharyngeal tubercle and carotid foramen. From the endoscopic endonasal perspective, in the median plane, the pharyngeal tubercle and the carotid foramen on both sides were located on a line. The average distance between the pharyngeal tubercle and anterior border of the external orifice of the carotid canal was measured as 25.2 ± 3.2 mm. In the paramedian plane, the PPICA was located between the levator veli palatini muscle (LVPM) and the stylopharyngeal muscle (SPM) in upper parapharyngeal space in all specimens, and the distance from the posterior border of the LVPM to the anterior border of the SPM was recorded as 15.1 ± 2.8 mm at the level of the carotid foramen. The distance from the attachment of the LVPM to the anterior border of the external orifice of the carotid canal was about 5.1 ± 0.2 mm. The fully developed stylopharyngeal fascia (SPhF) was observed in 10 cases, and the PPICA was always anteriorly enclosed by and adhered to the SPhF.