Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or their center-specific criteria for LT,along with the AFP cutoff values.The wait time for LT from downstaging was at least 4–6 wk in all centers.Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52%of the centers.Approximately 65%of the centers preferred to start everolimus between 1 and 3 months post-LT.CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%.The aim of transplantation is to achieve at least a 60%5-year disease free survival rate,which will provide relief to the prediction of an HCC surge over the next 20 years.The current worldwide criteria(Milan/UCSF)may have a higher 5-year survival(>70%);however,the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment,with much lower survival rates.To make predictions for 2040,we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome.With more advanced technology and better donor outcomes,LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

University of California Santa Barbara 2007 Global Medicine Conference——Integrating Chinese and Western Medicine:The View from China

From May 3 through May 6, 2007, the University of California, Santa Barbara （UCSB）＇s Global Medicine Project, and Santa Barbara Cottage Hospital cosponsored a conference entitled, “Integrating Chinese and Western Medicine： The View from China”. A select group of the most prominent doctors in China accepted an invitation to visit UCSB to share their research, case studies, and specific treatment protocols that successfully combine Western medicine and ancient Chinese healing practices to alleviate the suffering caused by some of the most difficult diseases confronting humanity. In China, this type of treatment has been used effectively for more than four decades, and was presented by a group of doctors and research scholars who are the central figures in the evolution of this important paradigm for healing in the 21st Century.

The President of the California Institute of Technology and the Chancellor of the University of California at Santa Barbara Visit Tsinghua

The President of the Califomia Institute of Technology Professor Jean-Lou Chameau and the Chancellor of the University of California at Santa Barbara Professor Henry Yang both delivered speeches in the Tsinghua Global Vision Lecture Series during their Tsinghua University visit on August 25, 2009.

The University of California,Berkeley

The roots of the University of California go back to the gold rush days of 1849,when the drafters of the State Constitution,a group of vigorous and farsighted people,required the legislature to "encourage by all suitable means the promotion of intellectual,scientific,moral and agricultural improvement"of the people of California.These

President of the California Institute of Technology and Chancellor of the University of California at Santa Barbara Visit Tsinghua University

The President of the California Institute of Technology Professor Jean-Lou Chameau and the Chancellor of the University of California at Santa Barbara Professor Henry Yang both delivered speeches in the Tsinghua Global Vision Lecture Series during their Tsinghua University visit on August 25, 2009. Tsinghua University President Gu Binglin welcomed Professor Chameau and Professor Yang and outlined for them the latest developments at Tsinghua University. The three university presidents expressed the hope that more cooperation in the future could be built between their universities. They discussed collaboration in research and student exchange during their talks.

University of California, Berkeley

The University of California, Berkeley, is the oldest and flagship campus of the ten-campus University of California system.

Transport of chemical signals in systemic acquired resistance

Systemic acquired resistance （SAR） is a form of broad-spectrum resistance induced in response to local infections that protects uninfected parts against subsequent secondary infections by related or unrelated pathogens. SAR signaling requires two parallel branches, one regulated by salicylic acid （SA）. and theother by azelaic acid （AzA） and glycerol-3-phosphate （G3P）. AzA and G3P function downstream of the free radicals nitric oxide （NO） and reactive oxygen species （ROS）. During SAR, SA, AzA and G3P accumulate in the infected leaves, but only a small portion of these is transported to distal uninfected leaves. SA is preferen- tially transported via the apoplast, whereas phloem loading of AzA and G3P occurs via the symplast. The symplastic transport of AzA and G3P is regulated by gating of the plasmodesmata （PD）. The PD localizing proteins, PDLP1 and PDLP5, regulate SAR by regulating PD gating as well as the subcellular partitioning of a SAR-associated protein.

Molecular regulation of sucrose catabolism and sugar transport for development~ defence and phloem function

Sucrose （Suc） is the major end product of photosynthesis in mesophyll cells of most vascular plants. It is loaded into phloem of mature leaves for long-distance translocation to non-photosynthetic organs where it is unloaded for diverse uses. Clearly, Suc transport and metabolism is central to plant growth and development and the functionality of the entire vascular system. Despite vast information in the literature about the physiological roles of individual sugar metabolic enzymes and transporters, there is a lack of systematic evaluation about their molecular regulation from transcriptional to post-translational levels. Knowledge on this topic is essential for understanding and improving plant development, optimizing resource distri- bution and increasing crop productivity. We therefore focused our analyses on molecular control of key players in Suc metabolism and transport, including： （i） the identifica- tion of promoter elements responsive to sugars and hormones or targeted by transcription factors and micro- RNAs degrading transcripts of target genes; and （ii） modulation of enzyme and transporter activities through protein-protein interactions and other post-translational modifications. We have highlighted major remaining questions and discussed opportunities to exploit current understanding to gain new insights into molecular control of carbon partitioning for improving plant performance.

A novel wheat NAC transcription factor,Ta NAC_(30), negatively regulates resistance of wheat to stripe rust

NAC transcription factors are widespread in the plant kingdom and play essential roles in the transcriptional regulation of defense responses. In this study, we isolated a novel NAC transcription factor gene, TaNAC30, from a cDNA library constructed from wheat （Triticum aestivum） plants inoculated with the stripe rust pathogen Puccinia striiformis f. sp. tritici （Pst）. TaNAC30 contains a typical NAM domain and localizes to the nucleus. Yeast one-hybrid assays revealed that TaNAC30 exhibits transcriptional activity and that its C-terminus is necessary for the activation of transcription. Expression of TaNAC30 increased when host plants were infected with a virulent race （CYR31） of the rust fungus Pst. Silencing of TaNAC30 by virus-induced gene silencing inhibited colonization of the virulent Psi isolate CYR31. Moreover, detailed histological analyses showed that silencing of TaNAC30 enhanced resistance to Pst by inducing a significant increase in the accumulation of H2O2. Finally, we overexpressed TaNAC30 in fission yeast and determined that cell viability was severely reduced in TaNAC30-transformed cells grown on medium containing H2O2. These results suggest that TaNAC30 negatively regulates plant resistance in a compatible wheat-Psi interaction.

What actually is the Münch hypothesis?A short history of assimilate transport by mass flow

In the 192os, the German forestry scientist Ernst M{Jnch postulated that photo-assimilate transport is a mass flow driven by osmotically induced pressure gradients between source organs （high turgot） and sink organs （lower turgor）. Two crucial components of MOnch＇s hypothesis, the translocation by mass flow from sources to sinks and the osmotic mechanism of pressure flow, were established notions at the time, but had been developed by two institutionally separated groups of scholars. A conceptual separation of wholepplant biology from cellular physiology had followed the institutional separation of forestry science from botany in German-speaking central Europe during the so-called Humboldtian reforms, and was reinforced by the delayed institutionalization of plant physiology as an academic discipline. Munch did not invent a novel concept, but accomplished an integration of the organism-focused and the cell-focused research traditions, reducing the polarization that had evolved when research universities emerged in central Europe. Post-Munch debates about the validity of his hypothesis focused increasingly on the suitability of available research methodologies, especially the electron microscope and the proper interpretation of the results it produced. The present work reconstructs the influence of the dynamic scientific and non-scientific context on the history of the Munch hypothesis.

Implications of nitrogen phloem loading for carbon metabolism and transport during Arabidopsis development

Metabolite transport processes and primary metabolism are highly interconnected. This study exam- ined the importance of source-to-sink nitrogen partition- ing, and associated nitrogen metabolism for carbon capture, transport and usage. Specifically, Arabidopsis aap8 （AMINO ACID PERMEASE 8） mutant lines were analyzed to resolve the consequences of reduced amino acid phloem loading for source leaf carbon metabolism, sucrose phloem transport and sink development during vegetative and reproductive growth phase. Results showed that decreased amino acid transport had a negative effect on sink development of aap8 lines throughout the life cycle, leading to an overall decrease in plant biomass. During vegetative stage, photosynthe- sis and carbohydrate levels were decreased in aap8 leaves, while expression of carbon metabolism and transport genes, as well as sucrose phloem transport were not affected despite reduced sink strength. However, when aap8 plants transitioned to reproductive phase, carbon fixation and assimilation as well as sucrose partitioning to siliques were strongly decreased. Overall, this work demonstrates that phloem loading of nitrogen has varying implications for carbon fixation, assimilation and source-to-sink allocation depending on plant growth stage. It further suggests alterations in source-sink relationships, and regulation of carbon metabolism and transport by sink strength in a development-dependent manner.

Plant xylem hydraulics:What we understand,current research,and future challenges

Herein we review the current state-of-the-art of plant hydraulics in the context of plant physiology, ecology, and evolution, focusing on current and future research opportunities. We explain the physics of water transport in plants and the limits of this transport system, highlighting the relationships between xylem structure and function. We describe the great variety of techniques existing for evaluating xylem resistance to cavitation. We address several methodological issues and their connec- tion with current debates on conduit refilling and exponentially shaped vulnerability curves. We analyze the trade-offs existing between water transport safety and efficiency. We also stress how little information is available on molecular biology of cavitation and the potential role of aquaporins in conduit refilling. Finally, we draw attention to how plant hydraulic traits can be used for modeling stomatal responses to environmental variables and climate change, including drought mortality.

Sucrose transporters and plasmodesmal regulation in passive phloem loading

An essential step for the distribution of carbon throughout the whole plant is the loading of sugars into the phloem in source organs. In many plants, accumulation of sugars in the sieve element-companion cell （SE-CC） complex is mediated and regulated by active processes. However, for poplar and many other tree species, a passive symplasmic mechanism of phloem loading has been proposed, characterized by symplasmic continuity along the pre-phloem pathway and the absence of active sugar accumulation in the SE-CC complex. A high overall leaf sugar concentration is thought to enable diffusion of sucrose into the phloem. In this review, we critically evaluate current evidence regarding the mechanism of passive syrnplasmic phloem loading, with a focus on the potential influence of active sugar transport and plasmo- desmal regulation. The limited experimental data, com- bined with theoretical considerations, suggest that a concomitant operation of passive symplasmic and active phloem loading in the same minor vein is unlikely. However, active sugar transport could well play an important role in how passively loading plants might modulate the rate of sugar export from leaves. Insights into the operation of this mechanism has direct implications for our understanding of how these plants utilize assimilated carbon.

Sucrose transporter2 contributes to maize growth,development,and crop yield

During daylight, plants produce excess photo- synthates, including sucrose, which is temporarily stored in the vacuole. At night, plants remobilize sucrose to sustain metabolism and growth. Based on homology to other sucrose transporter （SUT） proteins, we hypothesized the maize （Zea mays） SUCROSE TRANSPORTER2 （ZmSUT2） protein functions as a sucrose/H^＋ symporter on the vacuolar membrane to export transiently stored sucrose. To understand the biological role of ZmSut2, we examined its spatial and temporal gene expression, determined the protein subcellular localization, and characterized loss-of- function mutations. ZmSut2 mRNA was ubiquitously expressed and exhibited diurnal cycling in transcript abundance. Expressing a translational fusion of ZmSUT2 fused to a red fluorescent protein in maize mesophyll cell protoplasts revealed that the protein localized to the tonoplast. Under field conditions, zmsut2 mutant plants grew slower, possessed smaller tassels and ears, and produced fewer kernels when compared to wild-type siblings, zmsut2 mutants also accumulated two-fold more sucrose, glucose, and fructose as well as starch in source leaves compared to wild type. These findings suggest （i） ZmSUT2 functions to remobilize sucrose out of the vacuole for subsequent use in growing tissues; and （ii） its function provides an important contribution to maize development and agronomic yield.

The fungal UmSrt1 and maize ZmSUT1 sucrose transporters battle for plant sugar resources

The biotrophic fungus Ustilago maydis causes corn smut disease, inducing tumor formation in its host Zea mays. Upon infection, the fungal hyphae invaginate the plasma membrane of infected maize ceils, establishing an interface where pathogen and host are separated only by their plasma membranes. At this interface the fungal and maize sucrose transporters, UmSrtl and ZmSUT1, compete for extracellular sucrose in the corn smut/maize pathos- ystem. Here we biophysically characterized ZmSUT1 and UmSrtl in Xenopus oocytes with respect to their voltage-, pH- and substrate-dependence and determined affinities toward protons and sucrose. In contrast to ZmSUT% UmSrtl has a high affinity for sucrose and is relatively pH- and voltage-independent. Using these quantitative parameters, we developed a mathematical model to simulate the competition for extracellular sucrose at the contact zone between the fungus and the host plant. This approach revealed that UmSrtl exploits the apoplastic sucrose resource, which forces the plant transporter into a sucrose export mode providing the fungus with sugar from the phloem. Importantly, the high sucrose concen- tration in the phloem appeared disadvantageous for the ZmSUT1 preventing sucrose recovery from the apoplastic space in the fungus/plant interface.

Nicotiana attenuata's capacity to interact with arbuscular mycorrhiza alters its competitive ability and elicits major changes in the leaf transcriptome

To study the local and systemic effects of arbuscular mycorrhizal fungal （AMF） colonization, Nicotiana attenuata plants impaired in their interactions with AMF due to silencing of a calcium- and calmodulin dependent protein kinase （inverted repreat （ir）CCaMK） were grown competitively in pairs with empty vector （EV） plants, with and without two different types of inoculum. When inoculated, EV plants strongly outperformed irCCaMK plants. Foliar transcript profiling revealed that AMF colonization significantly changed gene expression of P-starvation and -transporter genes in irCCaMK plants. The Phtl family phosphate transporter NaPT5 was not only specifically induced in roots after AMF colonization, but also in leaves of AMF-colonized irCCaMK plants, and in plants grown under low Pi conditions in the absence of AMF. The P-starvation signature of inoculated irCCaMK plants corresponded with increases in selected amino acids and phenolic compounds in leaves. We also found a strong AMF-induced increase in amino acids and phenolic metabolites in roots. Plants impaired in their interactions with AMF clearly have a fitness disadvantage when competing for limited soil nutrients with a fully functional isogenic line. The additional role of the AMF-induced Phtl family transporter NaPT5 in leaves under P-starvation conditions will require further experiments to fully resolve.

Plant genetics enters the nano age?

Plant transformation has for many years relied on agrobacterium infection or biolistic particle delivery. However, these two methods are limited to model plant systems or a small number of crop species. This commentary highlights recent developments in the nanoparticle-mediated transformation that havethe potential to revolutionize how plants are trans- formed.